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(2E,6E)-3,7,10-trimethylundeca-2,6-dienyl diphosphate + NADPH
diphosphate + ?
-
weak
-
?
(2E,6E)-3,7,11-trimethyldodeca-2,6-dienyl diphosphate + NADPH
diphosphate + ?
-
-
-
?
(2E,6E)-3,7,12-trimethyltrideca-2,6-dienyl diphosphate + NADPH
diphosphate + ?
-
weak
-
?
(2E,6E)-3,7-dimethyldodeca-2,6-dienyl diphosphate + NADPH
diphosphate + ?
-
-
-
?
(2E,6E)-3,7-dimethyltetradeca-2,6-dienyl diphosphate + NADPH
diphosphate + ?
-
weak
-
?
(2E,6E)-3,7-dimethyltrideca-2,6-dienyl diphosphate + NADPH
diphosphate + ?
-
weak
-
?
(2E,6E)-3,7-dimethylundeca-2,6-dienyl diphosphate + NADPH
diphosphate + ?
-
weak
-
?
(2E,6E)-farnesyl diphosphate + NADH + H+
squalene + diphosphate + NAD+
-
-
-
?
(2E,6E)-farnesyl diphosphate + NADPH + H+
squalene + diphosphate + NADP+
-
-
-
?
(E,E)-7-desmethylfarnesyl diphosphate + NADPH
6,19-didesmethylsqualene + NADP+ + diphosphate
-
at 60% of the efficiency that farnesyl diphosphate is converted to squalene
in absence of farnesyl diphosphate, 6-desmethylsqualene is produced in presence of farnesyl diphosphate
?
10,11-dihydrofarnesyl diphosphate + NADPH
2,3,22,23-tetrahydrosqualene + NADP+ + diphosphate
-
at 60% of the efficiency that farnesyl diphosphate is converted to squalene
-
?
2 (2E,6E)-farnesyl diphosphate
diphosphate + presqualene diphosphate
2 (2E,6E)-farnesyl diphosphate + NADPH + H+
squalene + 2 diphosphate + NADP+
2 farnesyl diphosphate
presqualene diphosphate + diphosphate
2-methylfarnesyl diphosphate + NADPH
11-methylsqualene + NADP+ + diphosphate
3-demethylfarnesyl diphosphate + NADPH
10-demethylsqualene + NADP+ + diphosphate
farnesyl diphosphate
12,13-cis-dehydrosqualene + diphosphate
farnesyl diphosphate + farnesyl diphosphate
diphosphate + presqualene diphosphate
farnesyl diphosphate + NAD(P)H
squalene + diphosphate + NAD(P)+
farnesyl diphosphate + NAD(P)H + H+
squalene + diphosphate + NAD(P)+
farnesyl diphosphate + NADPH + H+
squalene + diphosphate + NADP+
-
-
sole product
?
presqualene diphosphate + NAD(P)H
squalene + NAD(P)+ + diphosphate
presqualene diphosphate + NAD(P)H + H+
squalene + diphosphate + NAD(P)+
presqualene diphosphate + NADPH + H+
squalene + diphosphate + NADP+
additional information
?
-
2 (2E,6E)-farnesyl diphosphate

diphosphate + presqualene diphosphate
-
-
-
?
2 (2E,6E)-farnesyl diphosphate
diphosphate + presqualene diphosphate
first half-reaction
-
?
2 (2E,6E)-farnesyl diphosphate
diphosphate + presqualene diphosphate
first reaction
-
?
2 (2E,6E)-farnesyl diphosphate
diphosphate + presqualene diphosphate
first reaction
-
?
2 (2E,6E)-farnesyl diphosphate
diphosphate + presqualene diphosphate
-
-
?
2 (2E,6E)-farnesyl diphosphate + NADPH + H+

squalene + 2 diphosphate + NADP+
-
-
?
2 (2E,6E)-farnesyl diphosphate + NADPH + H+
squalene + 2 diphosphate + NADP+
the enzyme initially catalyzes the condensation of two molecules of farnesyl diphosphate (FPP) to form presqualene diphosphate (PSPP), and next converting PSPP to squalene in a reaction requiring NADPH and Mg2+
product analysis by GC-MS analysis
?
2 (2E,6E)-farnesyl diphosphate + NADPH + H+
squalene + 2 diphosphate + NADP+
-
-
?
2 (2E,6E)-farnesyl diphosphate + NADPH + H+
squalene + 2 diphosphate + NADP+
-
-
?
2 (2E,6E)-farnesyl diphosphate + NADPH + H+
squalene + 2 diphosphate + NADP+
-
-
?
2 (2E,6E)-farnesyl diphosphate + NADPH + H+
squalene + 2 diphosphate + NADP+
-
-
-
?
2 (2E,6E)-farnesyl diphosphate + NADPH + H+
squalene + 2 diphosphate + NADP+
-
-
?
2 (2E,6E)-farnesyl diphosphate + NADPH + H+
squalene + 2 diphosphate + NADP+
-
-
-
?
2 (2E,6E)-farnesyl diphosphate + NADPH + H+
squalene + 2 diphosphate + NADP+
-
-
?
2 (2E,6E)-farnesyl diphosphate + NADPH + H+
squalene + 2 diphosphate + NADP+
-
overall reaction
-
?
2 (2E,6E)-farnesyl diphosphate + NADPH + H+
squalene + 2 diphosphate + NADP+
overall reaction, the enzyme catalyzes the two-step reductive head-to-head condensation of two molecules of farnesyl pyrophosphate to form squalene using presqualene diphosphate (PSPP) as an intermediate
-
?
2 (2E,6E)-farnesyl diphosphate + NADPH + H+
squalene + 2 diphosphate + NADP+
overall reaction
-
?
2 (2E,6E)-farnesyl diphosphate + NADPH + H+
squalene + 2 diphosphate + NADP+
overall reaction
-
?
2 (2E,6E)-farnesyl diphosphate + NADPH + H+
squalene + 2 diphosphate + NADP+
-
-
?
2 (2E,6E)-farnesyl diphosphate + NADPH + H+
squalene + 2 diphosphate + NADP+
specific for, the enzyme catalyzes a head-to-head condensation reaction (1'-2,3-linked) between two molecules of farnesyl diphosphate (C15) forms a cyclopropylcarbinyl intermediate, presqualene diphosphate. The subsequent conversion of presqualene diphosphate to squalene involves an extensive rearrangement of the carbon skeleton and an NADPH-dependent reduction reaction
-
?
2 (2E,6E)-farnesyl diphosphate + NADPH + H+
squalene + 2 diphosphate + NADP+
-
-
?
2 (2E,6E)-farnesyl diphosphate + NADPH + H+
squalene + 2 diphosphate + NADP+
-
-
?
2 (2E,6E)-farnesyl diphosphate + NADPH + H+
squalene + 2 diphosphate + NADP+
-
-
?
2 (2E,6E)-farnesyl diphosphate + NADPH + H+
squalene + 2 diphosphate + NADP+
farnesyl diphosphate forms hydrogen bonds with enzyme residues Arg49, Arg74, Ser48, and Val47 of conserved 77DTVED81 motif
-
?
2 (2E,6E)-farnesyl diphosphate + NADPH + H+
squalene + 2 diphosphate + NADP+
-
-
?
2 (2E,6E)-farnesyl diphosphate + NADPH + H+
squalene + 2 diphosphate + NADP+
farnesyl diphosphate forms hydrogen bonds with enzyme residues Asp81, Asp217, Glu80, and Gln206 of conserved 77DTVED81 and 213DYLED217 motifs
-
?
2 (2E,6E)-farnesyl diphosphate + NADPH + H+
squalene + 2 diphosphate + NADP+
overall reaction
-
?
2 (2E,6E)-farnesyl diphosphate + NADPH + H+
squalene + 2 diphosphate + NADP+
overall reaction
-
?
2 (2E,6E)-farnesyl diphosphate + NADPH + H+
squalene + 2 diphosphate + NADP+
-
-
-
?
2 (2E,6E)-farnesyl diphosphate + NADPH + H+
squalene + 2 diphosphate + NADP+
-
-
?
2 (2E,6E)-farnesyl diphosphate + NADPH + H+
squalene + 2 diphosphate + NADP+
overall reaction
-
?
2 farnesyl diphosphate

presqualene diphosphate + diphosphate
-
-
-
?
2 farnesyl diphosphate
presqualene diphosphate + diphosphate
-
-
?
2 farnesyl diphosphate
presqualene diphosphate + diphosphate
-
-
-
?
2 farnesyl diphosphate
presqualene diphosphate + diphosphate
-
-
-
?
2 farnesyl diphosphate
presqualene diphosphate + diphosphate
-
-
-
?
2 farnesyl diphosphate
presqualene diphosphate + diphosphate
-
-
-
?
2 farnesyl diphosphate
presqualene diphosphate + diphosphate
-
-
-
?
2 farnesyl diphosphate
presqualene diphosphate + diphosphate
-
assay at pH 7.2, 30°C, 3 h
-
?
2 farnesyl diphosphate
presqualene diphosphate + diphosphate
-
-
in absence of NADPH, formation of presqualene diphosphate
?
2-methylfarnesyl diphosphate + NADPH

11-methylsqualene + NADP+ + diphosphate
-
-
-
?
2-methylfarnesyl diphosphate + NADPH
11-methylsqualene + NADP+ + diphosphate
-
-
-
?
3-demethylfarnesyl diphosphate + NADPH

10-demethylsqualene + NADP+ + diphosphate
-
-
-
?
3-demethylfarnesyl diphosphate + NADPH
10-demethylsqualene + NADP+ + diphosphate
-
-
-
?
farnesyl diphosphate

12,13-cis-dehydrosqualene + diphosphate
-
-
-
?
farnesyl diphosphate
12,13-cis-dehydrosqualene + diphosphate
-
in presence of Mn2+
12-cis-dehydrosqualene + diphosphate
?
farnesyl diphosphate
12,13-cis-dehydrosqualene + diphosphate
-
-
-
?
farnesyl diphosphate + farnesyl diphosphate

diphosphate + presqualene diphosphate
-
-
-
?
farnesyl diphosphate + farnesyl diphosphate
diphosphate + presqualene diphosphate
-
-
?
farnesyl diphosphate + farnesyl diphosphate
diphosphate + presqualene diphosphate
-
enzyme may be important during response to infection and inflammation
-
?
farnesyl diphosphate + farnesyl diphosphate
diphosphate + presqualene diphosphate
-
first pathway-specific enzyme in cholesterol biosynthesis
-
?
farnesyl diphosphate + farnesyl diphosphate
diphosphate + presqualene diphosphate
-
-
-
?
farnesyl diphosphate + farnesyl diphosphate
diphosphate + presqualene diphosphate
-
-
-
?
farnesyl diphosphate + farnesyl diphosphate
diphosphate + presqualene diphosphate
-
squalene is the first sterol intermediate in cholesterol biosynthesis
-
?
farnesyl diphosphate + farnesyl diphosphate
diphosphate + presqualene diphosphate
-
enzyme may be important during response to infection and inflammation
-
?
farnesyl diphosphate + farnesyl diphosphate
diphosphate + presqualene diphosphate
-
-
-
?
farnesyl diphosphate + farnesyl diphosphate
diphosphate + presqualene diphosphate
-
-
-
?
farnesyl diphosphate + farnesyl diphosphate
diphosphate + presqualene diphosphate
-
-
-
?
farnesyl diphosphate + farnesyl diphosphate
diphosphate + presqualene diphosphate
-
-
-
?
farnesyl diphosphate + farnesyl diphosphate
diphosphate + presqualene diphosphate
-
-
-
?
farnesyl diphosphate + farnesyl diphosphate
diphosphate + presqualene diphosphate
-
-
-
?
farnesyl diphosphate + farnesyl diphosphate
diphosphate + presqualene diphosphate
-
-
-
?
farnesyl diphosphate + farnesyl diphosphate
diphosphate + presqualene diphosphate
-
-
-
?
farnesyl diphosphate + farnesyl diphosphate
diphosphate + presqualene diphosphate
-
-
-
?
farnesyl diphosphate + farnesyl diphosphate
diphosphate + presqualene diphosphate
-
first pathway-specific enzyme in cholesterol biosynthesis
-
?
farnesyl diphosphate + farnesyl diphosphate
diphosphate + presqualene diphosphate
-
essential enzyme in cholesterol biosynthetic pathway
-
?
farnesyl diphosphate + NAD(P)H

squalene + diphosphate + NAD(P)+
-
-
-
?
farnesyl diphosphate + NAD(P)H
squalene + diphosphate + NAD(P)+
-
-
-
?
farnesyl diphosphate + NAD(P)H
squalene + diphosphate + NAD(P)+
-
-
-
?
farnesyl diphosphate + NAD(P)H
squalene + diphosphate + NAD(P)+
-
-
-
?
farnesyl diphosphate + NAD(P)H
squalene + diphosphate + NAD(P)+
-
-
-
?
farnesyl diphosphate + NAD(P)H
squalene + diphosphate + NAD(P)+
-
-
-
?
farnesyl diphosphate + NAD(P)H
squalene + diphosphate + NAD(P)+
-
-
-
?
farnesyl diphosphate + NAD(P)H
squalene + diphosphate + NAD(P)+
-
-
-
?
farnesyl diphosphate + NAD(P)H
squalene + diphosphate + NAD(P)+
-
-
-
?
farnesyl diphosphate + NAD(P)H
squalene + diphosphate + NAD(P)+
-
-
-
?
farnesyl diphosphate + NAD(P)H
squalene + diphosphate + NAD(P)+
-
-
-
?
farnesyl diphosphate + NAD(P)H
squalene + diphosphate + NAD(P)+
-
-
-
?
farnesyl diphosphate + NAD(P)H
squalene + diphosphate + NAD(P)+
-
-
presqualene diphosphate and squalene are produced in a ratio of 6:1
?
farnesyl diphosphate + NAD(P)H
squalene + diphosphate + NAD(P)+
-
-
-
?
farnesyl diphosphate + NAD(P)H + H+

squalene + diphosphate + NAD(P)+
-
-
-
?
farnesyl diphosphate + NAD(P)H + H+
squalene + diphosphate + NAD(P)+
-
-
-
?
presqualene diphosphate + NAD(P)H

squalene + NAD(P)+ + diphosphate
-
-
-
?
presqualene diphosphate + NAD(P)H
squalene + NAD(P)+ + diphosphate
-
in presence of reducing pyridine nucleotide, preferably NADPH, squalene is formed, in absence of reducing cofactor the rate of the condensation reaction is lower and all of the product accumulates as presqualene diphosphate
-
?
presqualene diphosphate + NAD(P)H
squalene + NAD(P)+ + diphosphate
-
-
-
?
presqualene diphosphate + NAD(P)H
squalene + NAD(P)+ + diphosphate
-
-
-
?
presqualene diphosphate + NAD(P)H
squalene + NAD(P)+ + diphosphate
-
-
-
?
presqualene diphosphate + NAD(P)H
squalene + NAD(P)+ + diphosphate
-
in presence of reducing pyridine nucleotide, preferably NADPH, squalene is formed, in absence of reducing cofactor the rate of the condensation reaction is lower and all of the product accumulates as presqualene diphosphate
-
?
presqualene diphosphate + NAD(P)H
squalene + NAD(P)+ + diphosphate
-
in presence of reducing pyridine nucleotide, preferably NADPH, squalene is formed, in absence of reducing cofactor the rate of the condensation reaction is lower and all of the product accumulates as presqualene diphosphate
-
?
presqualene diphosphate + NAD(P)H
squalene + NAD(P)+ + diphosphate
-
presqualene diphosphate synthetase and squalene synthetase are copurified during isolation
-
?
presqualene diphosphate + NAD(P)H
squalene + NAD(P)+ + diphosphate
-
a single active site catalyzes both reactions
-
?
presqualene diphosphate + NAD(P)H
squalene + NAD(P)+ + diphosphate
-
one protein with 2 catalytic sites may be involved in synthesis of presqualene diphosphate and for its reduction to squalene
-
?
presqualene diphosphate + NAD(P)H
squalene + NAD(P)+ + diphosphate
-
the polymeric form of the enzyme also catalyzes the reduction of presqualene diphosphate by NADPH to squalene
-
?
presqualene diphosphate + NAD(P)H
squalene + NAD(P)+ + diphosphate
-
in presence of reducing pyridine nucleotide, preferably NADPH, squalene is formed, in absence of reducing cofactor the rate of the condensation reaction is lower and all of the product accumulates as presqualene diphosphate
-
?
presqualene diphosphate + NAD(P)H + H+

squalene + diphosphate + NAD(P)+
-
-
-
?
presqualene diphosphate + NAD(P)H + H+
squalene + diphosphate + NAD(P)+
-
-
?
presqualene diphosphate + NAD(P)H + H+
squalene + diphosphate + NAD(P)+
-
-
-
?
presqualene diphosphate + NAD(P)H + H+
squalene + diphosphate + NAD(P)+
-
-
-
?
presqualene diphosphate + NAD(P)H + H+
squalene + diphosphate + NAD(P)+
-
-
-
?
presqualene diphosphate + NAD(P)H + H+
squalene + diphosphate + NAD(P)+
second reaction
-
?
presqualene diphosphate + NAD(P)H + H+
squalene + diphosphate + NAD(P)+
second reaction
-
?
presqualene diphosphate + NAD(P)H + H+
squalene + diphosphate + NAD(P)+
-
-
-
?
presqualene diphosphate + NADPH + H+

squalene + diphosphate + NADP+
-
-
?
presqualene diphosphate + NADPH + H+
squalene + diphosphate + NADP+
-
-
-
?
presqualene diphosphate + NADPH + H+
squalene + diphosphate + NADP+
second half reaction
-
?
presqualene diphosphate + NADPH + H+
squalene + diphosphate + NADP+
-
-
-
?
presqualene diphosphate + NADPH + H+
squalene + diphosphate + NADP+
-
-
?
additional information

?
-
squalene and botryococcene are branched-chain, triterpene compounds that arise from the head-to-head condensation of two molecules of farnesyl diphosphate to yield 1'-1 and 1'-3 linkages, respectively. Different enzymes are responsible for botryococcene and squalene biosynthesis in the green alga Botryococcus braunii race B. The specificity for the 1'-1 and 1'-3 linkages is controlled by residues in the active sites that can mediate catalytic specificity. Identification of several amino acid positions contributing to the rearrangement of the cyclopropyl intermediate to squalene, The same positions do not appear to be sufficient to account for the cyclopropyl rearrangement to give botryococcene, oerview
-
?
additional information
?
-
-
squalene and botryococcene are branched-chain, triterpene compounds that arise from the head-to-head condensation of two molecules of farnesyl diphosphate to yield 1'-1 and 1'-3 linkages, respectively. Different enzymes are responsible for botryococcene and squalene biosynthesis in the green alga Botryococcus braunii race B. The specificity for the 1'-1 and 1'-3 linkages is controlled by residues in the active sites that can mediate catalytic specificity. Identification of several amino acid positions contributing to the rearrangement of the cyclopropyl intermediate to squalene, The same positions do not appear to be sufficient to account for the cyclopropyl rearrangement to give botryococcene, oerview
-
?
additional information
?
-
analysis of substrate specificity, overview
-
?
additional information
?
-
-
analysis of substrate specificity, overview
-
?
additional information
?
-
the catalytic process involves two reactions: firstly, two FPP molecules are condensed to form presqualene diphosphate (PSPP), an intermediate with a cyclopropane C1'-C2-C3 ring structure, and secondly, PSPP undergoes a NADPH-dependent rearrangement and reduction to generate the end product squalene
-
?
additional information
?
-
-
the catalytic process involves two reactions: firstly, two FPP molecules are condensed to form presqualene diphosphate (PSPP), an intermediate with a cyclopropane C1'-C2-C3 ring structure, and secondly, PSPP undergoes a NADPH-dependent rearrangement and reduction to generate the end product squalene
-
?
additional information
?
-
catalytic mechanism, overview
-
?
additional information
?
-
-
catalytic mechanism, overview
-
?
additional information
?
-
enzyme is key regulator not only for phytosterol but also for triterpene biosynthesis
-
?
additional information
?
-
-
enzyme is key regulator not only for phytosterol but also for triterpene biosynthesis
-
?
additional information
?
-
-
specificity overview
-
?
additional information
?
-
-
none of the following analogues gives nonpolar products: 7,11-dimethyl-3-ethyl-2,6,10-dodecatrienyl diphosphate, 6,7,10,11-tetrahydrofarnesyl diphosphate, 4-methylthiofarnesyl diphosphate, 4-fluorofarnesyl diphosphate
-
?
additional information
?
-
-
specificity overview
-
?
additional information
?
-
-
specificity overview
-
?
additional information
?
-
-
none of the following analogues gives nonpolar products: 7,11-dimethyl-3-ethyl-2,6,10-dodecatrienyl diphosphate, 6,7,10,11-tetrahydrofarnesyl diphosphate, 4-methylthiofarnesyl diphosphate, 4-fluorofarnesyl diphosphate
-
?
additional information
?
-
-
reaction is completely regioselective
-
?
additional information
?
-
-
no substrate: 6,7-dihydrofarnesyl diphosphate, 3-desmethylfarnesyl diphosphate
-
?
additional information
?
-
-
not metabolized: (E)-6,7,10,11-tetrahydrofarnesyl diphosphate
-
?
additional information
?
-
-
specificity overview
-
?
additional information
?
-
-
replacement of 3-methyl of farnesyl diphosphate by an ethyl group or introduction of a methyl group at C-4 results in a complete loss of activity
-
?
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
2 (2E,6E)-farnesyl diphosphate
diphosphate + presqualene diphosphate
2 (2E,6E)-farnesyl diphosphate + NADPH + H+
squalene + 2 diphosphate + NADP+
2 farnesyl diphosphate
presqualene diphosphate + diphosphate
farnesyl diphosphate + farnesyl diphosphate
diphosphate + presqualene diphosphate
presqualene diphosphate + NAD(P)H + H+
squalene + diphosphate + NAD(P)+
presqualene diphosphate + NADPH + H+
squalene + diphosphate + NADP+
additional information
?
-
2 (2E,6E)-farnesyl diphosphate

diphosphate + presqualene diphosphate
first half-reaction
-
-
?
2 (2E,6E)-farnesyl diphosphate
diphosphate + presqualene diphosphate
-
-
-
?
2 (2E,6E)-farnesyl diphosphate + NADPH + H+

squalene + 2 diphosphate + NADP+
-
-
-
?
2 (2E,6E)-farnesyl diphosphate + NADPH + H+
squalene + 2 diphosphate + NADP+
-
-
-
?
2 (2E,6E)-farnesyl diphosphate + NADPH + H+
squalene + 2 diphosphate + NADP+
-
-
-
?
2 (2E,6E)-farnesyl diphosphate + NADPH + H+
squalene + 2 diphosphate + NADP+
-
-
-
?
2 (2E,6E)-farnesyl diphosphate + NADPH + H+
squalene + 2 diphosphate + NADP+
-
-
-
-
?
2 (2E,6E)-farnesyl diphosphate + NADPH + H+
squalene + 2 diphosphate + NADP+
-
-
-
?
2 (2E,6E)-farnesyl diphosphate + NADPH + H+
squalene + 2 diphosphate + NADP+
-
-
-
-
?
2 (2E,6E)-farnesyl diphosphate + NADPH + H+
squalene + 2 diphosphate + NADP+
-
-
-
?
2 (2E,6E)-farnesyl diphosphate + NADPH + H+
squalene + 2 diphosphate + NADP+
overall reaction
-
-
?
2 (2E,6E)-farnesyl diphosphate + NADPH + H+
squalene + 2 diphosphate + NADP+
overall reaction
-
-
?
2 (2E,6E)-farnesyl diphosphate + NADPH + H+
squalene + 2 diphosphate + NADP+
-
-
-
?
2 (2E,6E)-farnesyl diphosphate + NADPH + H+
squalene + 2 diphosphate + NADP+
-
-
-
?
2 (2E,6E)-farnesyl diphosphate + NADPH + H+
squalene + 2 diphosphate + NADP+
-
-
-
?
2 (2E,6E)-farnesyl diphosphate + NADPH + H+
squalene + 2 diphosphate + NADP+
-
-
-
?
2 (2E,6E)-farnesyl diphosphate + NADPH + H+
squalene + 2 diphosphate + NADP+
-
-
-
?
2 (2E,6E)-farnesyl diphosphate + NADPH + H+
squalene + 2 diphosphate + NADP+
overall reaction
-
-
?
2 (2E,6E)-farnesyl diphosphate + NADPH + H+
squalene + 2 diphosphate + NADP+
overall reaction
-
-
?
2 (2E,6E)-farnesyl diphosphate + NADPH + H+
squalene + 2 diphosphate + NADP+
-
-
-
-
?
2 (2E,6E)-farnesyl diphosphate + NADPH + H+
squalene + 2 diphosphate + NADP+
-
-
-
?
2 (2E,6E)-farnesyl diphosphate + NADPH + H+
squalene + 2 diphosphate + NADP+
overall reaction
-
-
?
2 farnesyl diphosphate

presqualene diphosphate + diphosphate
-
-
-
-
?
2 farnesyl diphosphate
presqualene diphosphate + diphosphate
-
-
-
-
?
2 farnesyl diphosphate
presqualene diphosphate + diphosphate
-
-
-
-
?
2 farnesyl diphosphate
presqualene diphosphate + diphosphate
-
-
-
-
?
2 farnesyl diphosphate
presqualene diphosphate + diphosphate
-
-
-
-
?
2 farnesyl diphosphate
presqualene diphosphate + diphosphate
-
-
-
-
?
farnesyl diphosphate + farnesyl diphosphate

diphosphate + presqualene diphosphate
-
enzyme may be important during response to infection and inflammation
-
-
?
farnesyl diphosphate + farnesyl diphosphate
diphosphate + presqualene diphosphate
-
first pathway-specific enzyme in cholesterol biosynthesis
-
-
?
farnesyl diphosphate + farnesyl diphosphate
diphosphate + presqualene diphosphate
-
squalene is the first sterol intermediate in cholesterol biosynthesis
-
-
?
farnesyl diphosphate + farnesyl diphosphate
diphosphate + presqualene diphosphate
-
enzyme may be important during response to infection and inflammation
-
-
?
farnesyl diphosphate + farnesyl diphosphate
diphosphate + presqualene diphosphate
-
-
-
-
?
farnesyl diphosphate + farnesyl diphosphate
diphosphate + presqualene diphosphate
-
first pathway-specific enzyme in cholesterol biosynthesis
-
-
?
farnesyl diphosphate + farnesyl diphosphate
diphosphate + presqualene diphosphate
-
essential enzyme in cholesterol biosynthetic pathway
-
-
?
presqualene diphosphate + NAD(P)H + H+

squalene + diphosphate + NAD(P)+
-
-
-
-
?
presqualene diphosphate + NAD(P)H + H+
squalene + diphosphate + NAD(P)+
-
-
-
-
?
presqualene diphosphate + NAD(P)H + H+
squalene + diphosphate + NAD(P)+
-
-
-
-
?
presqualene diphosphate + NAD(P)H + H+
squalene + diphosphate + NAD(P)+
-
-
-
-
?
presqualene diphosphate + NAD(P)H + H+
squalene + diphosphate + NAD(P)+
-
-
-
-
?
presqualene diphosphate + NADPH + H+

squalene + diphosphate + NADP+
second half reaction
-
-
?
presqualene diphosphate + NADPH + H+
squalene + diphosphate + NADP+
-
-
-
-
?
presqualene diphosphate + NADPH + H+
squalene + diphosphate + NADP+
-
-
-
?
additional information

?
-
squalene and botryococcene are branched-chain, triterpene compounds that arise from the head-to-head condensation of two molecules of farnesyl diphosphate to yield 1'-1 and 1'-3 linkages, respectively. Different enzymes are responsible for botryococcene and squalene biosynthesis in the green alga Botryococcus braunii race B. The specificity for the 1'-1 and 1'-3 linkages is controlled by residues in the active sites that can mediate catalytic specificity. Identification of several amino acid positions contributing to the rearrangement of the cyclopropyl intermediate to squalene, The same positions do not appear to be sufficient to account for the cyclopropyl rearrangement to give botryococcene, oerview
-
-
?
additional information
?
-
-
squalene and botryococcene are branched-chain, triterpene compounds that arise from the head-to-head condensation of two molecules of farnesyl diphosphate to yield 1'-1 and 1'-3 linkages, respectively. Different enzymes are responsible for botryococcene and squalene biosynthesis in the green alga Botryococcus braunii race B. The specificity for the 1'-1 and 1'-3 linkages is controlled by residues in the active sites that can mediate catalytic specificity. Identification of several amino acid positions contributing to the rearrangement of the cyclopropyl intermediate to squalene, The same positions do not appear to be sufficient to account for the cyclopropyl rearrangement to give botryococcene, oerview
-
-
?
additional information
?
-
the catalytic process involves two reactions: firstly, two FPP molecules are condensed to form presqualene diphosphate (PSPP), an intermediate with a cyclopropane C1'-C2-C3 ring structure, and secondly, PSPP undergoes a NADPH-dependent rearrangement and reduction to generate the end product squalene
-
-
?
additional information
?
-
-
the catalytic process involves two reactions: firstly, two FPP molecules are condensed to form presqualene diphosphate (PSPP), an intermediate with a cyclopropane C1'-C2-C3 ring structure, and secondly, PSPP undergoes a NADPH-dependent rearrangement and reduction to generate the end product squalene
-
-
?
additional information
?
-
enzyme is key regulator not only for phytosterol but also for triterpene biosynthesis
-
-
?
additional information
?
-
-
enzyme is key regulator not only for phytosterol but also for triterpene biosynthesis
-
-
?
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(1-[[(1R,5S)-7-chloro-5-(2-chlorophenyl)-1-(2-methylpropyl)-2-oxo-1,2,4,5-tetrahydro-3H-3-benzazepin-3-yl]acetyl]piperidin-4-yl)acetic acid
-
-
(1-[[(3R,5S)-1-[3-(acetyloxy)-2,2-dimethylpropyl]-7-chloro-5-(2,3-dimethoxyphenyl)-2-oxo-1,2,3,5-tetrahydro-4,1-benzoxazepin-3-yl]acetyl]piperidin-4-yl)acetic acid
(1-[[(3R,5S)-7-chloro-5-(2,3-dimethoxyphenyl)-1-(3-hydroxy-2,2-dimethylpropyl)-2-oxo-1,2,3,5-tetrahydro-4,1-benzoxazepin-3-yl]acetyl]piperidin-4-yl)acetic acid
-
-
(1-[[(6S)-8-chloro-6-(2,3-dimethoxyphenyl)-1-(propan-2-yl)-6,10b-dihydro-1H,4H-[2]benzoxepino[4,5-c][1,2]oxazol-4-yl]acetyl]piperidin-4-yl)acetic acid
-
-
(1R,5S)-7-chloro-5-(2-methoxyphenyl)-1-(2-methylpropyl)-3-[2-oxo-2-(piperidin-1-yl)ethyl]-1,3,4,5-tetrahydro-2H-3-benzazepin-2-one
-
-
(2E)-3-[(1R,5S)-3-(carboxymethyl)-7-chloro-5-(2-chlorophenyl)-2-oxo-2,3,4,5-tetrahydro-1H-3-benzazepin-1-yl]-2-methylprop-2-enoic acid
-
-
(3R)-3-[[3-(benzyloxy)phenyl]ethynyl]-1-azabicyclo[2.2.2]octan-3-ol
-
IC50: 1500 nM
(3S)-1-(3-((4R,6S)-8-chloro-6-(2,3-dimethoxyphenyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl)propanoyl)-3-piperidine carboxylic acid
-
-
(3S)-1-[2-[(4R,6S)-8-chloro-6-(2,3-dimethoxyphenyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl]acetyl]-3-piperidinecarboxylic acid
-
-
1,3-diallyl-2-[3-(isopropylamino)propoxy]-9H-carbazole
-
50% inhibition at 250 nM
1-(2-[2-[(4R,6S)-8-chloro-6-(2,3-dimethoxyphenyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl]ethyl]-2H-1,2,3,4-tetrazol-5-yl)cyclopropanecarboxylic acid
-
-
1-(3-((4R,6S)-8-chloro-6-(2,3-dimethoxyphenyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl)propanoyl)-3-azetidine carboxylic acid
-
-
1-allyl-2-(3-anilinopropoxy)-9H-carbazole
-
50% inhibition at above 0.001 mM nM
1-allyl-2-[3-(benzylamino)propoxy]-9H-carbazole
-
50% inhibition at 63 nM
1-allyl-2-[3-(benzylamino)propoxy]-9H-carbazole hydrochloride
-
50% inhibition at 150 nM
1-allyl-2-[3-(cyclohexylamino)propoxy]-9H-carbazole
-
50% inhibition at 310 nM
1-allyl-2-[3-(cyclopropylamino)propoxy]-9H-carbazole
-
50% inhibition at 230 nM
1-allyl-2-[3-(isobutylamino)propoxy]-9H-carbazole
-
50% inhibition at 400 nM
1-allyl-2-[3-(isopropylamino)propoxy]-9H-carbazole
1-allyl-2-[3-(isopropylamino)propoxy]-9H-xanthen-9-one
1-[2-[(4R,6S)-8-chloro-6-(2,3-dimethoxyphenyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl]acetyl]-4-piperidinecarboxylic acid
-
-
1-[2-[(4R,6S)-8-chloro-6-(2,3-dimethoxyphenyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl]ethyl]-1H-1,2,3-triazole-4-carboxylic acid
-
-
1-[2-[(4R,6S)-8-chloro-6-(2,3-dimethoxyphenyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl]ethyl]-1H-pyrazole-4-carboxylic acid
-
-
1-[[(1R,5R)-7-chloro-5-(2,3-dimethoxyphenyl)-1-(2-methylpropyl)-2-oxo-1,2,4,5-tetrahydro-3H-3-benzazepin-3-yl]acetyl]piperidine-4-carboxylic acid
-
-
1-[[(1R,5S)-7-chloro-5-(2,3-dimethoxyphenyl)-1-(2-methylpropyl)-2-oxo-1,2,4,5-tetrahydro-3H-3-benzazepin-3-yl]acetyl]piperidine-4-carboxylic acid
-
-
1-[[(1R,5S)-7-chloro-5-(2-chlorophenyl)-1-(2-methylpropyl)-2-oxo-1,2,4,5-tetrahydro-3H-3-benzazepin-3-yl]acetyl]piperidine-4-carboxylic acid
-
-
1-[[(1R,5S)-7-chloro-5-(2-methoxyphenyl)-1-(2-methylpropyl)-2-oxo-1,2,4,5-tetrahydro-3H-3-benzazepin-3-yl]acetyl]piperidine-4-carboxylic acid
-
-
1-[[(1S,5S)-7-chloro-5-(2,3-dimethoxyphenyl)-1-(2-methylpropyl)-2-oxo-1,2,4,5-tetrahydro-3H-3-benzazepin-3-yl]acetyl]piperidine-4-carboxylic acid
-
-
1-[[(6S)-8-chloro-6-(2,3-dimethoxyphenyl)-1-(propan-2-yl)-6,10b-dihydro-1H,4H-[2]benzoxepino[4,5-c][1,2]oxazol-4-yl]acetyl]piperidine-4-carboxylic acid
-
-
2-(1-(3-[(4R,6S)-8-chloro-6-(2,3-dimethoxyphenyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl]propanoyl)-3-azetidinyl)acetic acid
-
-
2-(1-[2-[(4R,6S)-8-chloro-6-(2,3-dimethoxyphenyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl]acetyl]-4-piperidinyl)acetic acid
-
-
2-(1-[2-[(4R,6S)-8-chloro-6-(2,3-dimethoxyphenyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl]ethyl]-1H-1,2,3-triazol-4-yl)acetic acid
-
-
2-(1-[2-[(4R,6S)-8-chloro-6-(2,3-dimethoxyphenyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl]ethyl]-1H-1,2,3-triazol-5-yl)acetic acid
-
-
2-(1-[2-[(4R,6S)-8-chloro-6-(2,3-dimethoxyphenyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl]ethyl]-1H-pyrazol-3-yl)acetic acid
-
-
2-(1-[2-[(4R,6S)-8-chloro-6-(2,3-dimethoxyphenyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl]ethyl]-1H-pyrazol-4-yl)acetic acid
-
-
2-(1-[2-[(4R,6S)-8-chloro-6-(2,3-dimethoxyphenyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl]ethyl]-1H-pyrazol-5-yl)acetic acid
-
-
2-(1-[2-[(4S,6R)-8-chloro-6-(2,3-dimethoxyphenyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl]acetyl]-4-piperidinyl)acetic acid
-
-
2-(1-[2-[8-chloro-6-(2,3-dimethoxyphenyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl]acetyl]-4-piperidinyl)acetic acid
-
-
2-(1-[3-[(4R,6S)-8-chloro-6-(2,3-dimethoxyphenyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl]propanoyl]-4-piperidinyl)acetic acid
-
-
2-(2-[2-[(4R,6S)-8-chloro-6-(2,3-dimethoxyphenyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl)ethyl]-2H-1,2,3,4-tetrazol-5-yl]-2-methylpropanoic acid
-
-
2-(2-[2-[(4R,6S)-8-chloro-6-(2,3-dimethoxyphenyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl)ethyl]-2H-1,2,3,4-tetrazol-5-yl]acetic acid
-
-
2-(2-[2-[(4R,6S)-8-chloro-6-(2,3-dimethoxyphenyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl]ethyl]-1H-1,2,3,4-tetrazol-5-yl)acetic acid
-
-
2-(4-[2-[(4R,6S)-8-chloro-6-(2,3-dimethoxyphenyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl]acetyl]-1-piperazinyl)acetic acid
-
-
2-(4-[3-[(4R,6S)-8-chloro-6-(2,3-dimethoxyphenyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl]propanoyl]-2-oxo-1-piperazinyl)acetic acid
-
-
2-([2-[(4R,6S)-8-chloro-6-(2,3-dimethoxyphenyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl]acetyl]amino)acetic acid
-
-
2-[(1-[2-[(4R,6S)-8-chloro-6-(2,3-dimethoxyphenyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl]ethyl]-1H-1,2,3-triazol-4-yl)methoxy]-2-ethylbutanoic acid
-
-
2-[(1-[2-[(4R,6S)-8-chloro-6-(2,3-dimethoxyphenyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl]ethyl]-1H-1,2,3-triazol-4-yl)methoxy]-2-methylpropanoic acid
-
-
2-[(1-[2-[(4R,6S)-8-chloro-6-(2,3-dimethoxyphenyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl]ethyl]-1H-1,2,3-triazol-4-yl)methoxy]acetic acid
-
-
2-[(1-[3-[(4R,6S)-8-chloro-6-(2,3-dimethoxyphenyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl]propanoyl]-4-piperidinyl)methoxy]acetic acid
-
-
2-[(1-[3-[(4R,6S)-8-chloro-6-(2,3-dimethoxyphenyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl]propanoyl]-4-piperidinyl)oxy]acetic acid
-
-
2-[(2-[2-[(4R,6S)-8-chloro-6-(2,3-dimethoxyphenyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl]ethyl]-2H-1,2,3,4-tetrazol-5-yl)methoxy]-2-methylpropanoic acid
-
-
2-[(6S)-8-chloro-6-(2,3-dimethoxyphenyl)-1-(propan-2-yl)-6,10b-dihydro-1H,4H-[2]benzoxepino[4,5-c][1,2]oxazol-4-yl]-1-[(3R)-3-hydroxypyrrolidin-1-yl]ethanone
-
-
2-[1,8-dichloro-6-(2,3-dimethoxyphenyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl]acetic acid
-
-
2-[2-[(4R,6S)-8-chloro-6-(2,3-dimethoxyphenyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl]ethyl]-2H-1,2,3,4-tetrazol-5-carboxylic acid
-
-
2-[3-(isopropylamino)propoxy]-1-ethyl-9H-carbazole
-
50% inhibition at 460 nM
2-[3-(isopropylamino)propoxy]-9H-carbazole
2-[8-chloro-6-(1-naphthyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl]acetic acid
-
-
2-[8-chloro-6-(2,3-dichlorobenzoyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl]acetic acid
-
-
2-[8-chloro-6-(2,3-dihydro-1,4-benzodioxin-5-yl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl]acetic acid
-
-
2-[8-chloro-6-(2,3-dimethoxyphenyl)-1-(4-morpholinylmethyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl]acetic acid
-
-
2-[8-chloro-6-(2,3-dimethoxyphenyl)-1-[(dimethylamino)methyl]-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl]acetic acid
-
-
2-[8-chloro-6-(2,3-dimethoxyphenyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl]acetic acid
-
-
2-[[(2Z)-2-(1-azabicyclo(2.2.2)oct-3-ylidene)-2-fluoroethyl]oxy]-9H-carbazole
-
i.e. YM-53601, 50% inhibition at 90 nM
3-(2-[2-[(4R,6S)-8-chloro-6-(2,3-dimethoxyphenyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl]ethyl]-2H-1,2,3,4-tetrazol-5-yl)propanoic acid
-
-
3-(4-quinolin-6-ylphenyl)quinuclidin-3-ol
3-(biphenyl-4-yl)-2,3-dehydroquinuclidine
-
50% inhibition at 243 nM
3-(biphenyl-4-yl)-3-hydroxyquinuclidine
-
50% inhibition at 13 nM
3-(biphenyl-4-yl)-4'[(t-butyldimethylsilyl)oxy]-3-hydroxyquinuclidine
-
50% inhibition above 0.001 mM
3-(biphenyl-4-yl-4'-hydroxy)-2,3-dehydroquinuclidine
-
50% inhibition at 96 nM
3-(biphenyl-4-ylmethyl)-1-azabicyclo[2.2.2]oct-2-ene
-
IC50: 730 nM
3-([2-[(4R,6S)-8-chloro-6-(2,3-dimethoxyphenyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl]acetyl]amino)benzoic acid
-
-
3-([2-[(4R,6S)-8-chloro-6-(2,3-dimethoxyphenyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl]acetyl]amino)propionic acid
-
-
3-C-carboxy-2,4-dideoxy-2-dodec-11-en-1-ylpentaric acid
-
-
3-C-carboxy-2,4-dideoxy-2-dodecylpentaric acid
-
-
3-[(1-[3-[(4R,6S)-8-chloro-6-(2,3-dimethoxyphenyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl]propanoyl]-4-piperidinyl)oxy]propanoic acid
-
-
3-[(4R,6S)-8-chloro-6-(2,3-dimethoxyphenyl)-4H,6Hpyrrolo[1,2-a][4,1]benzoxazepin-4-yl]propionic acid
-
-
3-[[4-(benzyloxy)phenyl]ethynyl]-1-azabicyclo[2.2.2]oct-2-ene
-
IC50: 830 nM
4-[3-[(4R,6S)-8-chloro-6-(2,3-dimethoxyphenyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl]propanoyl]-2-morpholine carboxylic acid
-
-
6-([[(1R,5S)-7-chloro-5-(2-chlorophenyl)-1-(2-methylpropyl)-2-oxo-1,2,4,5-tetrahydro-3H-3-benzazepin-3-yl]acetyl]amino)hexanoic acid
-
-
Ammonium analogues
-
overview
-
BMS 187745
-
decrease of cholesterol or LDL
BPH-652
a phosphonosulfonate, binding structure
BPH-701
about 60% inhibition at 0.005 mM
CHQHNSMYC
an ennea-peptide, slight inhibition
CKTENMQSC
an ennea-peptide
CLGVHSSSC
an ennea-peptide
CLSPHSMFC
an ennea-peptide
CP-294838
a benzoxazepinone IC50 130 nM
CP-295697
a bisphosphonate, IC50: 20 nM
CQMHQLSSC
an ennea-peptide
CSGMKTTGC
an ennea-peptide
CSTLKVATC
an ennea-peptide
CSTPWHQWC
an ennea-peptide
CTVNWYPLC
an ennea-peptide
ethyl 4-(1-azabicyclo[2.2.2]oct-2-en-3-yl)benzoate
-
IC50: 50 nM
ethyl [(1R,5S)-7-chloro-5-(2-chlorophenyl)-1-(2-methylpropyl)-2-oxo-1,2,4,5-tetrahydro-3H-3-benzazepin-3-yl]acetate
-
-
Farnesyl methylenediphosphonate
a substrate analogue, potent enzyme inhibition
Guanidinium chloride
loss of 86% activity at 0.3M GdmCl, 50% at 0.2 M
methyl 2-[8-chloro-6-(2,3-dimethoxyphenyl)-4H,6Hpyrrolo[1,2-a][4,1]benzoxazepin-4-yl]acetate
-
-
N-isopropyl-biphenyloxypropylamine
-
50% inhibition at 93 nM
N-[[(3R,5S)-7-chloro-5-(2,3-dimethoxyphenyl)-1-(2,2-dimethylpropyl)-2-oxo-1,2,3,5-tetrahydro-4,1-benzoxazepin-3-yl]acetyl]-L-aspartic acid
-
-
NADP+
-
inhibitor of squalene synthesis
SPHS
a tetrapeptide, slight inhibition
Urea
loss of 81% activity at 2 M, 50% at 1 M
[(1R,5R)-7-chloro-1-(2-methylpropyl)-2-oxo-5-phenyl-1,2,4,5-tetrahydro-3H-3-benzazepin-3-yl]acetic acid
-
-
[(1R,5S)-1-benzyl-7-chloro-5-(2-chlorophenyl)-2-oxo-1,2,4,5-tetrahydro-3H-3-benzazepin-3-yl]acetic acid
-
-
[(1R,5S)-5-(2-bromophenyl)-7-chloro-1-(2-methylpropyl)-2-oxo-1,2,4,5-tetrahydro-3H-3-benzazepin-3-yl]acetic acid
-
-
[(1R,5S)-5-(2-chlorophenyl)-1-(2-methylpropyl)-2-oxo-1,2,4,5-tetrahydro-3H-3-benzazepin-3-yl]acetic acid
-
-
[(1R,5S)-5-(2-chlorophenyl)-7-fluoro-1-(2-methylpropyl)-2-oxo-1,2,4,5-tetrahydro-3H-3-benzazepin-3-yl]acetic acid
-
-
[(1R,5S)-5-(2-chlorophenyl)-7-methyl-1-(2-methylpropyl)-2-oxo-1,2,4,5-tetrahydro-3H-3-benzazepin-3-yl]acetic acid
-
-
[(1R,5S)-7-chloro-5-(2,3-dimethoxyphenyl)-1-(2-methylpropyl)-2-oxo-1,2,4,5-tetrahydro-3H-3-benzazepin-3-yl]acetic acid
-
-
[(1R,5S)-7-chloro-5-(2-chlorophenyl)-1-(2-hydroxy-2-methylpropyl)-2-oxo-1,2,4,5-tetrahydro-3H-3-benzazepin-3-yl]acetic acid
-
-
[(1R,5S)-7-chloro-5-(2-chlorophenyl)-1-(2-methylpropyl)-2-oxo-1,2,4,5-tetrahydro-3H-3-benzazepin-3-yl]acetic acid
-
-
[(1R,5S)-7-chloro-5-(2-methoxyphenyl)-1-(2-methylpropyl)-2-oxo-1,2,4,5-tetrahydro-3H-3-benzazepin-3-yl]acetic acid
-
-
[(4R,6R)-8-chloro-6-(2,3-dimethoxyphenyl)-1-(propan-2-yl)-6,10b-dihydro-1H,4H-[2]benzoxepino[4,5-c][1,2]oxazol-4-yl]acetic acid
-
-
[(4R,6S)-8-chloro-6-(2,3-dimethoxyphenyl)-1-(propan-2-yl)-6,10b-dihydro-1H,4H-[2]benzoxepino[4,5-c][1,2]oxazol-4-yl]acetic acid
-
-
[(4S,6R)-8-chloro-6-(2,3-dimethoxyphenyl)-1-(propan-2-yl)-6,10b-dihydro-1H,4H-[2]benzoxepino[4,5-c][1,2]oxazol-4-yl]acetic acid
-
-
[(4S,6S)-8-chloro-6-(2,3-dimethoxyphenyl)-1-(propan-2-yl)-6,10b-dihydro-1H,4H-[2]benzoxepino[4,5-c][1,2]oxazol-4-yl]acetic acid
-
-
[(6S)-8-chloro-6-(2,3-dimethoxyphenyl)-1-(propan-2-yl)-6,10b-dihydro-1H,4H-[2]benzoxepino[4,5-c][1,2]oxazol-4-yl]acetic acid
-
-
(1-[[(3R,5S)-1-[3-(acetyloxy)-2,2-dimethylpropyl]-7-chloro-5-(2,3-dimethoxyphenyl)-2-oxo-1,2,3,5-tetrahydro-4,1-benzoxazepin-3-yl]acetyl]piperidin-4-yl)acetic acid

-
i.e. lapaquistat acetate or TAK-475
(1-[[(3R,5S)-1-[3-(acetyloxy)-2,2-dimethylpropyl]-7-chloro-5-(2,3-dimethoxyphenyl)-2-oxo-1,2,3,5-tetrahydro-4,1-benzoxazepin-3-yl]acetyl]piperidin-4-yl)acetic acid
-
i.e. lapaquistat acetate or TAK-475
1-allyl-2-[3-(isopropylamino)propoxy]-9H-carbazole

-
50% inhibition at 32 nM
1-allyl-2-[3-(isopropylamino)propoxy]-9H-carbazole
-
50% inhibition at 66 nM
1-allyl-2-[3-(isopropylamino)propoxy]-9H-xanthen-9-one

-
50% inhibition at 120 nM
1-allyl-2-[3-(isopropylamino)propoxy]-9H-xanthen-9-one
-
50% inhibition at 120 nM
2-[3-(isopropylamino)propoxy]-9H-carbazole

-
50% inhibition at 810 nM
2-[3-(isopropylamino)propoxy]-9H-carbazole
-
50% inhibition at 110 nM
3-(4-quinolin-6-ylphenyl)quinuclidin-3-ol

-
i.e. RPR107393, 50% inhibition at 57 nM
3-(4-quinolin-6-ylphenyl)quinuclidin-3-ol
-
i.e. RPR107393, 50% inhibition at 68 nM
BMS-188494

-
-
BMS-188494
-
decrease of cholesterol or LDL
BMS-188494
-
no induction of myotoxicity
EP2302

-
-
EP2302
-
decrease of cholesterol or LDL
EP2302
-
decrease of cholesterol and triglyceride biosynthesis
EP2306

-
decrease of cholesterol or LDL
EP2306
-
decrease of cholesterol and triglyceride biosynthesis
ER-27856

-
-
ER-27856
-
decrease of cholesterol biosynthesis
ER-27856
-
decrease of cholesterol biosynthesis
ER-28448

-
decrease of cholesterol biosynthesis
ER-28448
-
decrease of cholesterol biosynthesis
farnesyl diphosphate

-
no inhibition of presqualene diphosphate synthase reaction; substrate inhibitor of squalene synthase reaction
farnesyl diphosphate
-
substrate inhibitor of squalene synthase reaction
lapaquistat

-
lipid-lowering effect
lapaquistat
-
lipid-lowering effect
lapaquistat
-
decrease of cholesterol or LDL
lapaquistat
-
lipid-lowering effect
lapaquistat
-
lipid-lowering effect
RPR107393

-
reduction in plasma cholesterol concentrations
RPR107393
-
reduction of plasman cholesterol concentrations
RPR107393
-
inhibition of cholesterol biosynthesis and reduced plasma total cholesterol levels
squalestatin

-
hypolipidemic effects but potential toxicity because of high levels of urinary dicarboxylic acid
squalestatin
-
hypolipidemic effects but potential toxicity because of high levels of urinary dicarboxylic acid
TAK-475

-
-
YM-53601

-
decrease of non-high-density lipoprotein cholesterol
YM-53601
-
reduction of non-high-density lipoprotein cholesterol concentrations
YM-53601
-
decrease of non-high-density lipoprotein cholesterol
YM-53601
-
reduction of non-high-density lipoprotein cholesterol concentrations
YM-53601
-
decrease of non-high-density lipoprotein cholesterol
zaragozic acid

-
hypolipidemic effects but potential toxicity because of high levels of urinary dicarboxylic acid
zaragozic acid
IC50 0.7 nM
zaragozic acid
-
competitive to farnesyl diphosphate
zaragozic acid
competitive type of inhibition
zaragozic acid
-
hypolipidemic effects but potential toxicity because of high levels of urinary dicarboxylic acid
zaragozic acid
-
decrease in plasma cholesterol
zaragozic acid A

-
0.04 mM
zaragozic acid A
-
enzyme binding induces a local conformational change in the substrate binding site, and its C-6 acyl group also extends over to the cofactor binding cavity, enzyme-inhibitor binding structure and thermodynamics, detailed overview
zaragozic acid A
is a potent inhibitor of mammalian SSN and also a competitive inhibitor of recombinant Leishmania donovani SSN, 50% inhibition at 100 nM
zaragozic acid A
-
inhibition of squalene synthase. Administration also significantly increases the rate of degradation of hepatic low density lipoprotein receptor protein, and increases proprotein convertase subtilisin/kexin type 9 mRNA and protein levels in concert with an increase in hepatic low density lipoprotein receptor mRNA levels, low density lipoprotein turnover, and decreases in serum cholesterol levels
zaragozic acid A
-
pH 7.2, 37°C
additional information

-
identification and optimization of tetrahydro-2H-3-benzazepin-2-ones as squalene synthase inhibitors, overview
-
additional information
-
4H,6H-[2]benzoxepino[4,5-c][1,2]oxazoles as squalene synthase inhibitors, design, synthesis, structure-activity relationship, and pharmacological profiles, overview
-
additional information
discovering peptide inhibitors of human squalene synthase through screening the phage-displayed cyclic peptide c7c library, molecular modelling and ADMET predictions of the selected peptides, using the crystal structure PDB 1EZF, a homo-trimer protein complex (with inhibitors CP-320473, CP-458003 and CP-424677), as the target, overview. The inhibitory peptides have potentials to develop cholesterol-lowering therapeutics. The ligand-protein interaction analysis also reveals that the inner hydrophobic pocketis a critical site of human enzyme for inhibition. No binding of peptide CPWWYGPWC. Cytotoxicity effects of different inhibitors, and protein-ligand interaction analysis, overview
-
additional information
-
discovering peptide inhibitors of human squalene synthase through screening the phage-displayed cyclic peptide c7c library, molecular modelling and ADMET predictions of the selected peptides, using the crystal structure PDB 1EZF, a homo-trimer protein complex (with inhibitors CP-320473, CP-458003 and CP-424677), as the target, overview. The inhibitory peptides have potentials to develop cholesterol-lowering therapeutics. The ligand-protein interaction analysis also reveals that the inner hydrophobic pocketis a critical site of human enzyme for inhibition. No binding of peptide CPWWYGPWC. Cytotoxicity effects of different inhibitors, and protein-ligand interaction analysis, overview
-
additional information
evaluation of the structure of substrate/inhibitor-binding sites via homology modeling, overview. Supplementation of any type of detergent inhibits the enzyme activity during purification
-
additional information
-
evaluation of the structure of substrate/inhibitor-binding sites via homology modeling, overview. Supplementation of any type of detergent inhibits the enzyme activity during purification
-
additional information
-
peroxisomal squalene synthase is inhibited by sonication, microsomal enzyme not
-
additional information
-
design, synthesis, and identification of highly potent benzhydrol derivatives as squalene synthase inhibitors, design of tricyclic pyrrolobenzoxazepine derivatives, overview
-
additional information
overexpression of the enzyme's C-terminal domain containing a hinge domain from fungi, not from animals or plants, leads to growth inhibition of wild-type yeast
-
additional information
-
overexpression of the enzyme's C-terminal domain containing a hinge domain from fungi, not from animals or plants, leads to growth inhibition of wild-type yeast
-
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0.0014
(1-[[(1R,5S)-7-chloro-5-(2-chlorophenyl)-1-(2-methylpropyl)-2-oxo-1,2,4,5-tetrahydro-3H-3-benzazepin-3-yl]acetyl]piperidin-4-yl)acetic acid
Homo sapiens
-
pH and temperature not specified in the publication
0.000213
(1-[[(3R,5S)-1-[3-(acetyloxy)-2,2-dimethylpropyl]-7-chloro-5-(2,3-dimethoxyphenyl)-2-oxo-1,2,3,5-tetrahydro-4,1-benzoxazepin-3-yl]acetyl]piperidin-4-yl)acetic acid
Homo sapiens
-
pH and temperature not specified in the publication
0.00026
(1-[[(3R,5S)-7-chloro-5-(2,3-dimethoxyphenyl)-1-(3-hydroxy-2,2-dimethylpropyl)-2-oxo-1,2,3,5-tetrahydro-4,1-benzoxazepin-3-yl]acetyl]piperidin-4-yl)acetic acid
Homo sapiens
-
pH and temperature not specified in the publication
0.000131
(1-[[(6S)-8-chloro-6-(2,3-dimethoxyphenyl)-1-(propan-2-yl)-6,10b-dihydro-1H,4H-[2]benzoxepino[4,5-c][1,2]oxazol-4-yl]acetyl]piperidin-4-yl)acetic acid
Homo sapiens
-
pH and temperature not specified in the publication
0.00037
(1R,5S)-7-chloro-5-(2-methoxyphenyl)-1-(2-methylpropyl)-3-[2-oxo-2-(piperidin-1-yl)ethyl]-1,3,4,5-tetrahydro-2H-3-benzazepin-2-one
Homo sapiens
-
pH and temperature not specified in the publication
0.0055
(2E)-3-[(1R,5S)-3-(carboxymethyl)-7-chloro-5-(2-chlorophenyl)-2-oxo-2,3,4,5-tetrahydro-1H-3-benzazepin-1-yl]-2-methylprop-2-enoic acid
Homo sapiens
-
pH and temperature not specified in the publication
0.0015
(3R)-3-[[3-(benzyloxy)phenyl]ethynyl]-1-azabicyclo[2.2.2]octan-3-ol
Trypanosoma cruzi
-
IC50: 1500 nM
0.0000014
(3S)-1-(3-((4R,6S)-8-chloro-6-(2,3-dimethoxyphenyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl)propanoyl)-3-piperidine carboxylic acid
Rattus norvegicus
-
pH 7.2-7.5, 37°C
0.0000023
(3S)-1-[2-[(4R,6S)-8-chloro-6-(2,3-dimethoxyphenyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl]acetyl]-3-piperidinecarboxylic acid
Rattus norvegicus
-
pH 7.2-7.5, 37°C
0.0000017
1-(2-[2-[(4R,6S)-8-chloro-6-(2,3-dimethoxyphenyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl]ethyl]-2H-1,2,3,4-tetrazol-5-yl)cyclopropanecarboxylic acid
Rattus norvegicus
-
pH 7.2-7.5, 37°C
0.0000022
1-(3-((4R,6S)-8-chloro-6-(2,3-dimethoxyphenyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl)propanoyl)-3-azetidine carboxylic acid
Rattus norvegicus
-
pH 7.2-7.5, 37°C
0.0000034
1-[2-[(4R,6S)-8-chloro-6-(2,3-dimethoxyphenyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl]acetyl]-4-piperidinecarboxylic acid
Rattus norvegicus
-
pH 7.2-7.5, 37°C
0.00000059
1-[2-[(4R,6S)-8-chloro-6-(2,3-dimethoxyphenyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl]ethyl]-1H-1,2,3-triazole-4-carboxylic acid
Rattus norvegicus
-
pH 7.2-7.5, 37°C
0.0000021
1-[2-[(4R,6S)-8-chloro-6-(2,3-dimethoxyphenyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl]ethyl]-1H-pyrazole-4-carboxylic acid
Rattus norvegicus
-
pH 7.2-7.5, 37°C
0.00022
1-[[(1R,5R)-7-chloro-5-(2,3-dimethoxyphenyl)-1-(2-methylpropyl)-2-oxo-1,2,4,5-tetrahydro-3H-3-benzazepin-3-yl]acetyl]piperidine-4-carboxylic acid
Homo sapiens
-
pH and temperature not specified in the publication
0.00045
1-[[(1R,5S)-7-chloro-5-(2,3-dimethoxyphenyl)-1-(2-methylpropyl)-2-oxo-1,2,4,5-tetrahydro-3H-3-benzazepin-3-yl]acetyl]piperidine-4-carboxylic acid
Homo sapiens
-
pH and temperature not specified in the publication
0.00093
1-[[(1R,5S)-7-chloro-5-(2-chlorophenyl)-1-(2-methylpropyl)-2-oxo-1,2,4,5-tetrahydro-3H-3-benzazepin-3-yl]acetyl]piperidine-4-carboxylic acid
Homo sapiens
-
pH and temperature not specified in the publication
0.0005
1-[[(1R,5S)-7-chloro-5-(2-methoxyphenyl)-1-(2-methylpropyl)-2-oxo-1,2,4,5-tetrahydro-3H-3-benzazepin-3-yl]acetyl]piperidine-4-carboxylic acid
Homo sapiens
-
pH and temperature not specified in the publication
0.02
1-[[(1S,5S)-7-chloro-5-(2,3-dimethoxyphenyl)-1-(2-methylpropyl)-2-oxo-1,2,4,5-tetrahydro-3H-3-benzazepin-3-yl]acetyl]piperidine-4-carboxylic acid
Homo sapiens
-
pH and temperature not specified in the publication
0.000112
1-[[(6S)-8-chloro-6-(2,3-dimethoxyphenyl)-1-(propan-2-yl)-6,10b-dihydro-1H,4H-[2]benzoxepino[4,5-c][1,2]oxazol-4-yl]acetyl]piperidine-4-carboxylic acid
Homo sapiens
-
pH and temperature not specified in the publication
0.000007
2-(1-(3-[(4R,6S)-8-chloro-6-(2,3-dimethoxyphenyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl]propanoyl)-3-azetidinyl)acetic acid
Rattus norvegicus
-
pH 7.2-7.5, 37°C
0.0000013
2-(1-[2-[(4R,6S)-8-chloro-6-(2,3-dimethoxyphenyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl]acetyl]-4-piperidinyl)acetic acid
Rattus norvegicus
-
pH 7.2-7.5, 37°C
0.00000051
2-(1-[2-[(4R,6S)-8-chloro-6-(2,3-dimethoxyphenyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl]ethyl]-1H-1,2,3-triazol-4-yl)acetic acid
Rattus norvegicus
-
pH 7.2-7.5, 37°C
0.00000081
2-(1-[2-[(4R,6S)-8-chloro-6-(2,3-dimethoxyphenyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl]ethyl]-1H-1,2,3-triazol-5-yl)acetic acid
Rattus norvegicus
-
pH 7.2-7.5, 37°C
0.0000013
2-(1-[2-[(4R,6S)-8-chloro-6-(2,3-dimethoxyphenyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl]ethyl]-1H-pyrazol-3-yl)acetic acid
Rattus norvegicus
-
pH 7.2-7.5, 37°C
0.0000031
2-(1-[2-[(4R,6S)-8-chloro-6-(2,3-dimethoxyphenyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl]ethyl]-1H-pyrazol-4-yl)acetic acid
Rattus norvegicus
-
pH 7.2-7.5, 37°C
0.0000016
2-(1-[2-[(4R,6S)-8-chloro-6-(2,3-dimethoxyphenyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl]ethyl]-1H-pyrazol-5-yl)acetic acid
Rattus norvegicus
-
pH 7.2-7.5, 37°C
0.0006
2-(1-[2-[(4S,6R)-8-chloro-6-(2,3-dimethoxyphenyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl]acetyl]-4-piperidinyl)acetic acid
Rattus norvegicus
-
pH 7.2-7.5, 37°C
0.0000027
2-(1-[2-[8-chloro-6-(2,3-dimethoxyphenyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl]acetyl]-4-piperidinyl)acetic acid
Rattus norvegicus
-
pH 7.2-7.5, 37°C
0.0000024
2-(1-[3-[(4R,6S)-8-chloro-6-(2,3-dimethoxyphenyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl]propanoyl]-4-piperidinyl)acetic acid
Rattus norvegicus
-
pH 7.2-7.5, 37°C
0.0000011
2-(2-[2-[(4R,6S)-8-chloro-6-(2,3-dimethoxyphenyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl)ethyl]-2H-1,2,3,4-tetrazol-5-yl]-2-methylpropanoic acid
Rattus norvegicus
-
pH 7.2-7.5, 37°C
0.0000011
2-(2-[2-[(4R,6S)-8-chloro-6-(2,3-dimethoxyphenyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl)ethyl]-2H-1,2,3,4-tetrazol-5-yl]acetic acid
Rattus norvegicus
-
pH 7.2-7.5, 37°C
0.0000011
2-(2-[2-[(4R,6S)-8-chloro-6-(2,3-dimethoxyphenyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl]ethyl]-1H-1,2,3,4-tetrazol-5-yl)acetic acid
Rattus norvegicus
-
pH 7.2-7.5, 37°C
0.0000043
2-(4-[2-[(4R,6S)-8-chloro-6-(2,3-dimethoxyphenyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl]acetyl]-1-piperazinyl)acetic acid
Rattus norvegicus
-
pH 7.2-7.5, 37°C
0.0000022
2-(4-[3-[(4R,6S)-8-chloro-6-(2,3-dimethoxyphenyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl]propanoyl]-2-oxo-1-piperazinyl)acetic acid
Rattus norvegicus
-
pH 7.2-7.5, 37°C
0.0000023
2-([2-[(4R,6S)-8-chloro-6-(2,3-dimethoxyphenyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl]acetyl]amino)acetic acid
Rattus norvegicus
-
pH 7.2-7.5, 37°C
0.0000017
2-[(1-[2-[(4R,6S)-8-chloro-6-(2,3-dimethoxyphenyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl]ethyl]-1H-1,2,3-triazol-4-yl)methoxy]-2-ethylbutanoic acid
Rattus norvegicus
-
pH 7.2-7.5, 37°C
0.00000069
2-[(1-[2-[(4R,6S)-8-chloro-6-(2,3-dimethoxyphenyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl]ethyl]-1H-1,2,3-triazol-4-yl)methoxy]-2-methylpropanoic acid
Rattus norvegicus
-
pH 7.2-7.5, 37°C
0.00000068
2-[(1-[2-[(4R,6S)-8-chloro-6-(2,3-dimethoxyphenyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl]ethyl]-1H-1,2,3-triazol-4-yl)methoxy]acetic acid
Rattus norvegicus
-
pH 7.2-7.5, 37°C
0.0000009
2-[(1-[3-[(4R,6S)-8-chloro-6-(2,3-dimethoxyphenyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl]propanoyl]-4-piperidinyl)methoxy]acetic acid
Rattus norvegicus
-
pH 7.2-7.5, 37°C
0.0000008
2-[(1-[3-[(4R,6S)-8-chloro-6-(2,3-dimethoxyphenyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl]propanoyl]-4-piperidinyl)oxy]acetic acid
Rattus norvegicus
-
pH 7.2-7.5, 37°C
0.0000025
2-[(2-[2-[(4R,6S)-8-chloro-6-(2,3-dimethoxyphenyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl]ethyl]-2H-1,2,3,4-tetrazol-5-yl)methoxy]-2-methylpropanoic acid
Rattus norvegicus
-
pH 7.2-7.5, 37°C
0.000162
2-[(6S)-8-chloro-6-(2,3-dimethoxyphenyl)-1-(propan-2-yl)-6,10b-dihydro-1H,4H-[2]benzoxepino[4,5-c][1,2]oxazol-4-yl]-1-[(3R)-3-hydroxypyrrolidin-1-yl]ethanone
Homo sapiens
-
pH and temperature not specified in the publication
0.0000016
2-[1,8-dichloro-6-(2,3-dimethoxyphenyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl]acetic acid
Rattus norvegicus
-
pH 7.2-7.5, 37°C
0.00000089
2-[2-[(4R,6S)-8-chloro-6-(2,3-dimethoxyphenyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl]ethyl]-2H-1,2,3,4-tetrazol-5-carboxylic acid
Rattus norvegicus
-
pH 7.2-7.5, 37°C
0.0006
2-[8-chloro-6-(1-naphthyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl]acetic acid
Rattus norvegicus
-
pH 7.2-7.5, 37°C
0.000052
2-[8-chloro-6-(2,3-dichlorobenzoyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl]acetic acid
Rattus norvegicus
-
pH 7.2-7.5, 37°C
0.00044
2-[8-chloro-6-(2,3-dihydro-1,4-benzodioxin-5-yl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl]acetic acid
Rattus norvegicus
-
pH 7.2-7.5, 37°C
0.0000076
2-[8-chloro-6-(2,3-dimethoxyphenyl)-1-(4-morpholinylmethyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl]acetic acid
Rattus norvegicus
-
pH 7.2-7.5, 37°C
0.00054
2-[8-chloro-6-(2,3-dimethoxyphenyl)-1-[(dimethylamino)methyl]-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl]acetic acid
Rattus norvegicus
-
pH 7.2-7.5, 37°C
0.0000033
2-[8-chloro-6-(2,3-dimethoxyphenyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl]acetic acid
Rattus norvegicus
-
pH 7.2-7.5, 37°C
0.00000085
3-(2-[2-[(4R,6S)-8-chloro-6-(2,3-dimethoxyphenyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl]ethyl]-2H-1,2,3,4-tetrazol-5-yl)propanoic acid
Rattus norvegicus
-
pH 7.2-7.5, 37°C
0.00073
3-(biphenyl-4-ylmethyl)-1-azabicyclo[2.2.2]oct-2-ene
Trypanosoma cruzi
-
IC50: 730 nM
0.000004
3-([2-[(4R,6S)-8-chloro-6-(2,3-dimethoxyphenyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl]acetyl]amino)benzoic acid
Rattus norvegicus
-
pH 7.2-7.5, 37°C
0.0000029
3-([2-[(4R,6S)-8-chloro-6-(2,3-dimethoxyphenyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl]acetyl]amino)propionic acid
Rattus norvegicus
-
pH 7.2-7.5, 37°C
0.0000014
3-[(1-[3-[(4R,6S)-8-chloro-6-(2,3-dimethoxyphenyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl]propanoyl]-4-piperidinyl)oxy]propanoic acid
Rattus norvegicus
-
pH 7.2-7.5, 37°C
0.0000031
3-[(4R,6S)-8-chloro-6-(2,3-dimethoxyphenyl)-4H,6Hpyrrolo[1,2-a][4,1]benzoxazepin-4-yl]propionic acid
Rattus norvegicus
-
pH 7.2-7.5, 37°C
0.00083
3-[[4-(benzyloxy)phenyl]ethynyl]-1-azabicyclo[2.2.2]oct-2-ene
Trypanosoma cruzi
-
IC50: 830 nM
0.0000016
4-[3-[(4R,6S)-8-chloro-6-(2,3-dimethoxyphenyl)-4H,6H-pyrrolo[1,2-a][4,1]benzoxazepin-4-yl]propanoyl]-2-morpholine carboxylic acid
Rattus norvegicus
-
pH 7.2-7.5, 37°C
0.0024
6-([[(1R,5S)-7-chloro-5-(2-chlorophenyl)-1-(2-methylpropyl)-2-oxo-1,2,4,5-tetrahydro-3H-3-benzazepin-3-yl]acetyl]amino)hexanoic acid
Homo sapiens
-
pH and temperature not specified in the publication
0.0001
chlorogenic acid
Sus scrofa
-
pH 7.4, 37°C
0.087
CKTE
Homo sapiens
pH and temperature not specified in the publication
0.064
CLSPHSMFC
Homo sapiens
pH and temperature not specified in the publication
0.00013
CP-294838
Homo sapiens
a benzoxazepinone IC50 130 nM
0.00002
CP-295697
Homo sapiens
a bisphosphonate, IC50: 20 nM
0.00000084
E5700
Trypanosoma cruzi
-
IC50: 0.84 nM
0.00000352
ER119884
Trypanosoma cruzi
-
IC50: 3.52 nM
0.00005
ethyl 4-(1-azabicyclo[2.2.2]oct-2-en-3-yl)benzoate
Trypanosoma cruzi
-
IC50: 50 nM
0.02
ethyl [(1R,5S)-7-chloro-5-(2-chlorophenyl)-1-(2-methylpropyl)-2-oxo-1,2,4,5-tetrahydro-3H-3-benzazepin-3-yl]acetate
Homo sapiens
-
pH and temperature not specified in the publication
0.00022
methyl 2-[8-chloro-6-(2,3-dimethoxyphenyl)-4H,6Hpyrrolo[1,2-a][4,1]benzoxazepin-4-yl]acetate
Rattus norvegicus
-
pH 7.2-7.5, 37°C
0.076
SMFC
Homo sapiens
pH and temperature not specified in the publication
0.09
WHQW
Homo sapiens
pH and temperature not specified in the publication
0.0000007
zaragozic acid
Homo sapiens
IC50 0.7 nM
0.0000955
zaragozic acid A
Thermosynechococcus elongatus
-
pH 7.2, 37°C
0.0153
[(1R,5R)-7-chloro-1-(2-methylpropyl)-2-oxo-5-phenyl-1,2,4,5-tetrahydro-3H-3-benzazepin-3-yl]acetic acid
Homo sapiens
-
pH and temperature not specified in the publication
0.02
[(1R,5S)-1-benzyl-7-chloro-5-(2-chlorophenyl)-2-oxo-1,2,4,5-tetrahydro-3H-3-benzazepin-3-yl]acetic acid
Homo sapiens
-
pH and temperature not specified in the publication
0.0022
[(1R,5S)-5-(2-bromophenyl)-7-chloro-1-(2-methylpropyl)-2-oxo-1,2,4,5-tetrahydro-3H-3-benzazepin-3-yl]acetic acid
Homo sapiens
-
pH and temperature not specified in the publication
0.02
[(1R,5S)-5-(2-chlorophenyl)-1-(2-methylpropyl)-2-oxo-1,2,4,5-tetrahydro-3H-3-benzazepin-3-yl]acetic acid
Homo sapiens
-
pH and temperature not specified in the publication
0.02
[(1R,5S)-5-(2-chlorophenyl)-7-fluoro-1-(2-methylpropyl)-2-oxo-1,2,4,5-tetrahydro-3H-3-benzazepin-3-yl]acetic acid
Homo sapiens
-
pH and temperature not specified in the publication
0.02
[(1R,5S)-5-(2-chlorophenyl)-7-methyl-1-(2-methylpropyl)-2-oxo-1,2,4,5-tetrahydro-3H-3-benzazepin-3-yl]acetic acid
Homo sapiens
-
pH and temperature not specified in the publication
0.0012
[(1R,5S)-7-chloro-5-(2,3-dimethoxyphenyl)-1-(2-methylpropyl)-2-oxo-1,2,4,5-tetrahydro-3H-3-benzazepin-3-yl]acetic acid
Homo sapiens
-
pH and temperature not specified in the publication
0.02
[(1R,5S)-7-chloro-5-(2-chlorophenyl)-1-(2-hydroxy-2-methylpropyl)-2-oxo-1,2,4,5-tetrahydro-3H-3-benzazepin-3-yl]acetic acid
Homo sapiens
-
pH and temperature not specified in the publication
0.0033
[(1R,5S)-7-chloro-5-(2-chlorophenyl)-1-(2-methylpropyl)-2-oxo-1,2,4,5-tetrahydro-3H-3-benzazepin-3-yl]acetic acid
Homo sapiens
-
pH and temperature not specified in the publication
0.0019
[(1R,5S)-7-chloro-5-(2-methoxyphenyl)-1-(2-methylpropyl)-2-oxo-1,2,4,5-tetrahydro-3H-3-benzazepin-3-yl]acetic acid
Homo sapiens
-
pH and temperature not specified in the publication
0.00142
[(4R,6R)-8-chloro-6-(2,3-dimethoxyphenyl)-1-(propan-2-yl)-6,10b-dihydro-1H,4H-[2]benzoxepino[4,5-c][1,2]oxazol-4-yl]acetic acid
Homo sapiens
-
pH and temperature not specified in the publication
0.000056
[(4R,6S)-8-chloro-6-(2,3-dimethoxyphenyl)-1-(propan-2-yl)-6,10b-dihydro-1H,4H-[2]benzoxepino[4,5-c][1,2]oxazol-4-yl]acetic acid
Homo sapiens
-
pH and temperature not specified in the publication
0.000169
[(4S,6R)-8-chloro-6-(2,3-dimethoxyphenyl)-1-(propan-2-yl)-6,10b-dihydro-1H,4H-[2]benzoxepino[4,5-c][1,2]oxazol-4-yl]acetic acid
Homo sapiens
-
pH and temperature not specified in the publication
0.0055
[(4S,6S)-8-chloro-6-(2,3-dimethoxyphenyl)-1-(propan-2-yl)-6,10b-dihydro-1H,4H-[2]benzoxepino[4,5-c][1,2]oxazol-4-yl]acetic acid
Homo sapiens
-
pH and temperature not specified in the publication
0.000223
[(6S)-8-chloro-6-(2,3-dimethoxyphenyl)-1-(propan-2-yl)-6,10b-dihydro-1H,4H-[2]benzoxepino[4,5-c][1,2]oxazol-4-yl]acetic acid
Homo sapiens
-
pH and temperature not specified in the publication
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evolution

phylogenetic analysis of SQS enzymes in plants shows highly similar conserved pattern including 77DTVED81 and 213DYLED217 motifs, which are rich in aspartic acids involved in FPP binding
evolution
phylogenetic analysis of SQS enzymes in plants shows highly similar conserved pattern including 77DTVED81 and 213DYLED217 motifs, which are rich in aspartic acids involved in FPP binding
evolution
the enzyme belongs to the isoprenoid biosynthesis enzymes class 1 superfamily
evolution
-
the enzyme belongs to the isoprenoid biosynthesis enzymes class 1 superfamily
malfunction

-
Inhibition of squalene synthase leads directly to a reduction in cholesterol biosynthesis and thus to a fall in plasma cholesterol levels. Plasma LDL-cholesterol and triglycerides are lowered by squalene synthase inhibitors
malfunction
-
modifications in region IV prevents SQS from undergoing the second half-reaction, indicating that this region may reasonably constitute a functional NADPH binding site
malfunction
enzyme overexpression in transgenic Withania somnifera plants affects the shoot elongation and multiplication, phenotype, overview
malfunction
the SQS inhibitors YM-53601 and zaragozic acid A decrease hepatitis C virus RNA, protein, and progeny production in HCV-infected cells without affecting cell viability, using the HCV JFH-1 strain and human hepatoma Huh-7.5.1-derived cells. siRNA-mediated knockdown of SQS leads to significantly reduced HCV production, confirming the enzyme acts as an antiviral target. A metabolic labeling study demonstrates that enzyme inhibitor YM-53601 suppresses the biosynthesis of cholesterol and cholesteryl esters at antiviral concentrations
metabolism

-
key enzyme in the isoprenoid pathway
metabolism
-
part of cholesterol biosynthesis pathway
metabolism
-
part of cholesterol biosynthesis pathway
metabolism
-
part of cholesterol biosynthesis pathway
metabolism
-
part of cholesterol biosynthesis pathway
metabolism
-
part of cholesterol biosynthesis pathway
metabolism
-
part of cholesterol biosynthesis pathway
metabolism
-
part of cholesterol synthesis pathway
metabolism
-
part of cholesterol synthesis pathway
metabolism
-
part of cholesterol synthesis pathway
metabolism
-
part of cholesterol synthesis pathway
metabolism
-
part of cholesterol synthesis pathway
metabolism
-
part of cholesterol synthesis pathway
metabolism
-
part of cholesterol synthesis pathway
metabolism
-
part of cholesterol synthesis pathway
metabolism
-
part of cholesterol synthesis pathway
metabolism
-
squalene synthase catalyzes the committed step of sterol synthesis
metabolism
-
squalene synthase catalyzes the conversion of farnesyl pyrophosphate into squalene by reductive condensation. This is a crucial step in cholesterol biosynthesis, squalene serves as the exclusive precursor for cholesterol
metabolism
squalene synthase catalyzes the first enzymatic step of the central isoprenoid pathway in sterol and triterpenoid biosynthesis
metabolism
squalene synthase is a key enzyme in the regulation of isoprenoid biosynthesis and is important in the withanolides biosynthesis pathway, overview
metabolism
-
squalene synthase is a key enzyme involved in antifungal steroidal glycoalkaloids biosynthesis. Steroidal glycoalkaloids are a family of nitrogenous secondary metabolites acting as phytoalexins, e.g. gamma-solamargine and its aglycone solasodine from Solanum nigrum inhibiting hyphae formation of Fusarium oxysporum
metabolism
squalene synthase is a major enzyme in the sterol biosynthetic pathway
metabolism
squalene synthase is the key enzyme of saponin biosynthesis pathway
metabolism
enzyme SQS operates at a branch point of the withanolide biosynthetic pathway regulating the metabolic flux and catalyzes the first committed step leading to the synthesis of different withanolides
metabolism
four major steps - substrate binding, condensation, intermediate formation and translocation - of the ordered sequential mechanisms involved in the 1'-1 isoprenoid biosynthetic pathway
metabolism
-
squalene synthase catalyzes the first committed step in sterol biosynthesis
metabolism
squalene synthase catalyzes the first committed step in sterol biosynthesis
metabolism
squalene synthase catalyzes the first committed step in sterol biosynthesis
metabolism
squalene synthase catalyzes the first committed step in sterol biosynthesis, role of squalene synthase in the ergosterol biosynthetic pathway of budding yeast, overview
metabolism
-
squalene synthase catalyzes the first step of sterol/hopanoid biosynthesis in the organism
metabolism
squalene synthase catalyzes the first step of sterol/hopanoid biosynthesis in the organism
metabolism
squalene synthase catalyzes the first step of sterol/hopanoid biosynthesis in the organism
metabolism
the enzyme catalyzes the first dedicated step in the biosynthesis of sterols and other triterpenoids
metabolism
the enzyme is a key enzyme in the isoprenoid biosynthesis
metabolism
-
the enzyme is involved in squalene synthesis and sterol metabolism
metabolism
-
the enzyme is a key enzyme in the isoprenoid biosynthesis
metabolism
-
squalene synthase is a major enzyme in the sterol biosynthetic pathway
physiological function

-
essential role in embryonic development
physiological function
-
influence on regulation of cholesterol metabolism
physiological function
-
influence on regulation of cholesterol metabolism
physiological function
-
influence on regulation of cholesterol metabolism
physiological function
-
influence on regulation of cholesterol metabolism
physiological function
-
influence on regulation of cholesterol metabolism
physiological function
-
influence on regulation of cholesterol metabolism
physiological function
-
influence on regulation of cholesterol metabolism
physiological function
-
influence on regulation of cholesterol metabolism
physiological function
squalene synthase catalyses an unusual head-to-head reductive dimerization of two molecules of farnesyl-pyrophosphate in a two-step reaction to form squalene
physiological function
squalene synthase functions as a key regulator in channeling the carbon flux into both the primary and secondary metabolite branches, and squalene synthase may play a regulatory role in directing triterpene intermediates and sterol pathways
physiological function
enzyme SQS plays an important role in regulating isoprenoid biosynthesis in eukaryotes
physiological function
SQS play an important regulatory role in phytosterol biosynthetic pathway
physiological function
-
squalene is biosynthesized via the head-to-head condensation of two molecules of farnesyl diphosphate, which is catalyzed by the single enzyme squalene synthase. Squalene is a precursor of thousands of bioactive triterpenoids
physiological function
squalene is biosynthesized via the head-to-head condensation of two molecules of farnesyl diphosphate, which is catalyzed by the single enzyme squalene synthase. Squalene is a precursor of thousands of bioactive triterpenoids
physiological function
squalene synthase is the rate-limiting enzyme located at the downstream of cholesterol synthesis pathway
physiological function
the catalytic domain performs the head-to-head dimerization of two molecules of farnesyl diphosphate to form squalene, a 30 carbon isoprenoid oxidized by squalene monooxygenase (Erg1) and cyclized by lanosterol synthase
physiological function
-
the enzyme is involved in squalene synthesis and sterol metabolism
physiological function
the enzyme squalene synthase catalyzes the first committed step in sterol biosynthesis by condensing two molecules of farnesyl diphosphate into squalene in two reaction steps
physiological function
the enzyme squalene synthase catalyzes the first committed step in sterol biosynthesis by condensing two molecules of farnesyl diphosphate into squalene in two reaction steps
physiological function
squalene and botryococcene are branched-chain, triterpene compounds that arise from the head-tohead condensation of two molecules of farnesyl diphosphate to yield 1'-1 and 1'-3 linkages, respectively