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Literature summary for 1.5.1.3 extracted from

  • Bolstad, D.B.; Bolstad, E.S.; Frey, K.M.; Wright, D.L.; Anderson, A.C.
    Structure-based approach to the development of potent and selective inhibitors of dihydrofolate reductase from Cryptosporidium (2008), J. Med. Chem., 51, 6839-6852.
    View publication on PubMedView publication on EuropePMC

Application

Application Comment Organism
drug development the enzyme is a possible target for treatment of cryptosporidiosis caused by the organism Cryptosporidium hominis

Cloned(Commentary)

Cloned (Comment) Organism
expression in Escherichia coli Cryptosporidium hominis

Inhibitors

Inhibitors Comment Organism Structure
2,4-diamino-5-[(R)-3-(3-methoxy-5-phenylphenyl)but-1-ynyl]-6-methylpyrimidine
-
Cryptosporidium hominis
2,4-diamino-5-[(S)-3-(3-methoxy-5-phenylphenyl)but-1-ynyl]-6-methylpyrimidine
-
Cryptosporidium hominis
2,4-diamino-5-[3-(3-methoxy-4-(2,6-diisopropylphenyl)phenyl)-but-1-ynyl]-6-methylpyrimidine
-
Cryptosporidium hominis
2,4-diamino-5-[3-(3-methoxy-4-(2,6-dimethylphenyl)phenyl)but-1-ynyl]-6-methylpyrimidine
-
Cryptosporidium hominis
2,4-diamino-5-[3-(3-methoxy-4-(2-methylphenyl)phenyl)but-1-ynyl]-6-methylpyrimidine
-
Cryptosporidium hominis
2,4-diamino-5-[3-(3-methoxy-4-phenylphenyl)but-1-ynyl]-6-methylpyrimidine
-
Cryptosporidium hominis
2,4-diamino-5-[3-(3-methoxy-5-(2,6-diisopropylphenyl)phenyl)-but-1-ynyl]-6-methylpyrimidine
-
Cryptosporidium hominis
2,4-diamino-5-[3-(3-methoxy-5-(2,6-dimethylphenyl)phenyl)but-1-ynyl]-6-methylpyrimidine
-
Cryptosporidium hominis
2,4-diamino-5-[3-(3-methoxy-5-(2-methylphenyl)phenyl)but-1-ynyl]-6-methylpyrimidine
-
Cryptosporidium hominis
2,4-diamino-5-[3-(3-methoxy-5-phenylphenyl)but-1-ynyl]-6-methylpyrimidine
-
Cryptosporidium hominis
6-methyl-5-[3-(3,4,5-trimethoxyphenyl)but-1-yn-1-yl]pyrimidine-2,4-diamine
-
Cryptosporidium hominis
additional information inhibitor design and synthesis, computational modeling, analysis of the interactions of the biphenyl compounds with the enzyme, and drug selectivity in comparison to the human enzyme, overview Cryptosporidium hominis

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
additional information Cryptosporidium hominis in Cryptosporidium, DHFR and thymidylate synthase are present as a bifunctional enzyme, DHFR-TS ?
-
?

Organism

Organism UniProt Comment Textmining
Cryptosporidium hominis
-
-
-

Purification (Commentary)

Purification (Comment) Organism
recombinant enzyme from Escherichia coli by methotrexate affinity chromatography Cryptosporidium hominis

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
additional information in Cryptosporidium, DHFR and thymidylate synthase are present as a bifunctional enzyme, DHFR-TS Cryptosporidium hominis ?
-
?

Synonyms

Synonyms Comment Organism
DHFR
-
Cryptosporidium hominis
DHFR-TS
-
Cryptosporidium hominis

IC50 Value

IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
0.0000011
-
-
Cryptosporidium hominis 2,4-diamino-5-[(R)-3-(3-methoxy-5-phenylphenyl)but-1-ynyl]-6-methylpyrimidine
0.0000018
-
-
Cryptosporidium hominis 2,4-diamino-5-[3-(3-methoxy-5-phenylphenyl)but-1-ynyl]-6-methylpyrimidine
0.0000021
-
-
Cryptosporidium hominis 2,4-diamino-5-[3-(3-methoxy-5-(2-methylphenyl)phenyl)but-1-ynyl]-6-methylpyrimidine
0.0000021
-
-
Cryptosporidium hominis 2,4-diamino-5-[3-(3-methoxy-5-(2,6-dimethylphenyl)phenyl)but-1-ynyl]-6-methylpyrimidine
0.0000074
-
-
Cryptosporidium hominis 2,4-diamino-5-[3-(3-methoxy-4-(2,6-dimethylphenyl)phenyl)but-1-ynyl]-6-methylpyrimidine
0.00001
-
-
Cryptosporidium hominis 2,4-diamino-5-[3-(3-methoxy-5-(2,6-diisopropylphenyl)phenyl)-but-1-ynyl]-6-methylpyrimidine
0.000016
-
-
Cryptosporidium hominis 2,4-diamino-5-[3-(3-methoxy-4-(2,6-diisopropylphenyl)phenyl)-but-1-ynyl]-6-methylpyrimidine
0.000019
-
-
Cryptosporidium hominis 2,4-diamino-5-[3-(3-methoxy-4-phenylphenyl)but-1-ynyl]-6-methylpyrimidine
0.00003
-
-
Cryptosporidium hominis 2,4-diamino-5-[(S)-3-(3-methoxy-5-phenylphenyl)but-1-ynyl]-6-methylpyrimidine
0.000036
-
-
Cryptosporidium hominis 2,4-diamino-5-[3-(3-methoxy-4-(2-methylphenyl)phenyl)but-1-ynyl]-6-methylpyrimidine
0.000038
-
-
Cryptosporidium hominis 6-methyl-5-[3-(3,4,5-trimethoxyphenyl)but-1-yn-1-yl]pyrimidine-2,4-diamine