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Literature summary for 1.15.1.1 extracted from

  • Zhang, Y.; Zhao, K.T.; Fox, S.G.; Kim, J.; Kirsch, D.R.; Ferrante, R.J.; Morimoto, R.I.; Silverman, R.B.
    Tertiary amine pyrazolones and their salts as inhibitors of mutant superoxide dismutase 1-dependent protein aggregation for the treatment of amyotrophic lateral sclerosis (2015), J. Med. Chem., 58, 5942-5949 .
    View publication on PubMedView publication on EuropePMC

Protein Variants

Protein Variants Comment Organism
G93A naturally occuring mutation, mutant SOD1-induced cytotoxicity protection Homo sapiens

Inhibitors

Inhibitors Comment Organism Structure
5-(((2,4-dichlorobenzyl)(propyl)amino)methyl)-1H-pyrazol-3(2H)-one EC50 value is 630 nM Homo sapiens
5-(((2,4-dichlorobenzyl)(propyl)amino)methyl)-1H-pyrazol-3(2H)-one EC50 value is 630 nM Mus musculus
5-(((3,5-dichlorobenzyl)(ethyl)amino)methyl)-1H-pyrazol-3(2H)-one EC50 value is 420 nM Homo sapiens
5-(((3,5-dichlorobenzyl)(ethyl)amino)methyl)-1H-pyrazol-3(2H)-one EC50 value is 420 nM Mus musculus
5-(((3,5-dichlorobenzyl)(isopropyl)amino)methyl)-1H-pyrazol-3(2H)-one EC50 value is 0.00108 mM Homo sapiens
5-(((3,5-dichlorobenzyl)(isopropyl)amino)methyl)-1H-pyrazol-3(2H)-one EC50 value is 0.00108 mM Mus musculus
5-(((3,5-dichlorobenzyl)(methyl)amino)methyl)-1H-pyrazol-3(2H)-one EC50 value is 480 nM Homo sapiens
5-(((3,5-dichlorobenzyl)(methyl)amino)methyl)-1H-pyrazol-3(2H)-one EC50 value is 480 nM Mus musculus
5-(((3,5-dichlorobenzyl)(propyl)amino)methyl)-1H-pyrazol-3(2H)-one EC50 value is 470 nM Homo sapiens
5-(((3,5-dichlorobenzyl)(propyl)amino)methyl)-1H-pyrazol-3(2H)-one EC50 value is 470 nM Mus musculus
5-(((3,5-dichlorophenethyl)(methyl)amino)methyl)-1H-pyrazol-3(2H)-one EC50 value is 0.00164 mM Homo sapiens
5-(((3,5-dichlorophenethyl)(methyl)amino)methyl)-1H-pyrazol-3(2H)-one EC50 value is 0.00164 mM Mus musculus
5-(((3-(3,5-dichlorophenyl)propyl)(methyl)amino)methyl)-1H-pyrazol-3(2H)-one EC50 value is 0.00332 mM Homo sapiens
5-(((3-(3,5-dichlorophenyl)propyl)(methyl)amino)methyl)-1H-pyrazol-3(2H)-one EC50 value is 0.00332 mM Mus musculus
5-((benzyl(3,5-dichlorobenzyl)amino)methyl)-1H-pyrazol-3(2H)-one EC50 value is 0.00245 mM Homo sapiens
5-((benzyl(3,5-dichlorobenzyl)amino)methyl)-1H-pyrazol-3(2H)-one EC50 value is 0.00245 mM Mus musculus
5-((cyclopropyl(3,5-dichlorobenzyl)amino)methyl)-1H-pyrazol-3(2H)-one EC50 value is 0.00134 mM Homo sapiens
5-((cyclopropyl(3,5-dichlorobenzyl)amino)methyl)-1H-pyrazol-3(2H)-one EC50 value is 0.00134 mM Mus musculus
5-[(3,5-dichlorophenoxy)methyl]-1,2-dihydro-3H-pyrazol-3-one EC50 value is 400 nM Homo sapiens
5-[(3,5-dichlorophenoxy)methyl]-1,2-dihydro-3H-pyrazol-3-one EC50 value is 400 nM Mus musculus
5-[[(3,5-dichlorophenyl)(methyl)amino]methyl]-1,2-dihydro-3H-pyrazol-3-one EC50 value is 570 nM Homo sapiens
5-[[(3,5-dichlorophenyl)(methyl)amino]methyl]-1,2-dihydro-3H-pyrazol-3-one EC50 value is 570 nM Mus musculus
di-N-(3,5-dichlorobenzyl)-N-methyl-1-(5-oxo-2,5-dihydro-1H-pyrazol-3-yl)methanaminium sulfate EC50 value is 480 nM Homo sapiens
di-N-(3,5-dichlorobenzyl)-N-methyl-1-(5-oxo-2,5-dihydro-1H-pyrazol-3-yl)methanaminium sulfate EC50 value is 480 nM Mus musculus
additional information pyrazolone derivatives are inhibitors of Cu/Zn superoxide dismutase 1 (SOD1)-dependent protein aggregation and are useful as drugs in treatment of amyotrophic lateral sclerosis (ALS). Design and synthesis of a series of tertiary amine-containing pyrazolones and their structure-activity relationships, conjugate salts greatly improved their solubility, overview Homo sapiens
additional information pyrazolone derivatives are inhibitors of Cu/Zn superoxide dismutase 1 (SOD1)-dependent protein aggregation and toxicity, and are useful as drugs in treatment of amyotrophic lateral sclerosis (ALS). Design and synthesis of a series of tertiary amine-containing pyrazolones and their structure-activity relationships, conjugate salts greatly improve their solubility, overview. Identification of several neuron-protection scaffolds based on mitigating protein aggregation and toxicity. A tertiary amine fragment is incorporated into the linker between the pyrazolone and the aryl group on the basis of principles of optimal brain exposure in CNS drug molecule design, the tertiary amine pyrazolone scaffolds exhibited superior properties for potential neuronal activity and in metabolic studies, such as microsomal stability, plasma stability, and Caco-2 permeability Mus musculus
N-(3,5-dichlorobenzyl)-N-methyl-1-(5-oxo-2,5-dihydro-1H-pyrazol-3-yl)methanaminium chloride EC50 value is 510 nM Homo sapiens
N-(3,5-dichlorobenzyl)-N-methyl-1-(5-oxo-2,5-dihydro-1H-pyrazol-3-yl)methanaminium chloride EC50 value is 510 nM Mus musculus
N-(3,5-dichlorobenzyl)-N-methyl-1-(5-oxo-2,5-dihydro-1H-pyrazol-3-yl)methanaminium citrate EC50 value is 480 nM Homo sapiens
N-(3,5-dichlorobenzyl)-N-methyl-1-(5-oxo-2,5-dihydro-1H-pyrazol-3-yl)methanaminium citrate EC50 value is 480 nM Mus musculus
N-(3,5-dichlorobenzyl)-N-methyl-1-(5-oxo-2,5-dihydro-1H-pyrazol-3-yl)methanaminium dibasic phosphate EC50 value is 480 nM Homo sapiens
N-(3,5-dichlorobenzyl)-N-methyl-1-(5-oxo-2,5-dihydro-1H-pyrazol-3-yl)methanaminium dibasic phosphate EC50 value is 480 nM Mus musculus
N-(3,5-dichlorobenzyl)-N-methyl-1-(5-oxo-2,5-dihydro-1H-pyrazol-3-yl)methanaminium L-tartrate EC50 value is 480 nM Homo sapiens
N-(3,5-dichlorobenzyl)-N-methyl-1-(5-oxo-2,5-dihydro-1H-pyrazol-3-yl)methanaminium L-tartrate EC50 value is 480 nM Mus musculus

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
2 superoxide + 2 H+ Mus musculus
-
O2 + H2O2
-
?
2 superoxide + 2 H+ Homo sapiens
-
O2 + H2O2
-
?

Organism

Organism UniProt Comment Textmining
Homo sapiens
-
-
-
Mus musculus
-
-
-

Source Tissue

Source Tissue Comment Organism Textmining
brain
-
Mus musculus
-
brain
-
Homo sapiens
-
Caco-2 cell
-
Homo sapiens
-
central nervous system
-
Mus musculus
-
central nervous system
-
Homo sapiens
-
spinal cord
-
Mus musculus
-
spinal cord
-
Homo sapiens
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
2 superoxide + 2 H+
-
Mus musculus O2 + H2O2
-
?
2 superoxide + 2 H+
-
Homo sapiens O2 + H2O2
-
?

Synonyms

Synonyms Comment Organism
SOD1
-
Mus musculus
SOD1
-
Homo sapiens
superoxide dismutase 1
-
Mus musculus
superoxide dismutase 1
-
Homo sapiens

General Information

General Information Comment Organism
malfunction pyrazolone derivatives are inhibitors of Cu/Zn superoxide dismutase 1 (SOD1)-dependent protein aggregation Mus musculus