Protein Variants | Comment | Organism |
---|---|---|
G93A | site-directed mutagenesis | Mus musculus |
Inhibitors | Comment | Organism | Structure |
---|---|---|---|
additional information | compound 2-[(3-iodophenyl)methylsulfanyl]-5-pyridin-4-yl-1,3,4-oxadiazole, a known protein kinase inhibitor, decreases enzyme mutant G93A-SOD1 expression in vitro and in the brain and spinal cord in vivo, but this compound has a biphasic dose response curve and a likely toxophore which limit its therapeutic window for chronic disease such as amyotrophic lateral sclerosis (ALS). Therefore, a focused library of analogues are tested for the ability to decrease SOD1 expression in vitro. This exercise results in the identification of a lead compound with improved drug-like characteristics and activity. Development of small molecules that reduce the expression of etiologically relevant toxic proteins, structureactivity relationships, overview. Compounds 3-[1-(3-hydroxypropyl)-1H-pyrrolo[2,3-b]pyridin-3-yl]-4-(pyrazin-2-yl)-1H-pyrrole-2,5-dione, 2-chloro-1-(4,5-dibromothiophen-2-yl)ethan-1-one, 2-bromo-1-(4-bromophenyl)ethan-1-one, 4-(5-[[(3-iodophenyl)methyl]sulfanyl]-1,3,4-oxadiazol-2-yl)pyridine, 4-(5-[[(3-methoxyphenyl)methyl]sulfanyl]-1,3,4-oxadiazol-2-yl)pyridine, 4-(5-[[(3-fluorophenyl)methyl]sulfanyl]-1,3,4-oxadiazol-2-yl)pyridine, 4-[5-([[4-(trifluoromethyl)phenyl]methyl]sulfanyl)-1,3,4-oxadiazol-2-yl]pyridine, 4-(5-[[(3-chlorophenyl)methyl]sulfanyl]-1,3,4-oxadiazol-2-yl)pyridine, 4-(5-[[(3-nitrophenyl)methyl]sulfanyl]-1,3,4-oxadiazol-2-yl)pyridine, 4-(5-[[(3-bromophenyl)methyl]sulfanyl]-1,3,4-oxadiazol-2-yl)pyridine, 4-(5-[[(4-methoxyphenyl)methyl]sulfanyl]-1,3,4-oxadiazol-2-yl)pyridine, 4-(5-[[(4-chlorophenyl)methyl]sulfanyl]-1,3,4-oxadiazol-2-yl)pyridine, 4-(5-[[(4-bromophenyl)methyl]sulfanyl]-1,3,4-oxadiazol-2-yl)pyridine, 4-(5-[[(4-iodophenyl)methyl]sulfanyl]-1,3,4-oxadiazol-2-yl)pyridine, 4-(5-[[(4-fluorophenyl)methyl]sulfanyl]-1,3,4-oxadiazol-2-yl)pyridine, 4-(5-[[(4-methylphenyl)methyl]sulfanyl]-1,3,4-oxadiazol-2-yl)pyridine, 4-(5-[[(4-nitrophenyl)methyl]sulfanyl]-1,3,4-oxadiazol-2-yl)pyridine, 4-(5-[[(4-nitrophenyl)methyl]sulfanyl]-1,3,4-oxadiazol-2-yl)pyridine suppress the enzyme expression | Mus musculus |
Metals/Ions | Comment | Organism | Structure |
---|---|---|---|
Cu2+ | a Cu-ZnSOD | Mus musculus | |
Zn2+ | a Cu-ZnSOD | Mus musculus |
Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
2 superoxide + 2 H+ | Mus musculus | - |
O2 + H2O2 | - |
? |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Mus musculus | - |
- |
- |
Source Tissue | Comment | Organism | Textmining |
---|---|---|---|
brain | - |
Mus musculus | - |
spinal cord | - |
Mus musculus | - |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
2 superoxide + 2 H+ | - |
Mus musculus | O2 + H2O2 | - |
? |
Synonyms | Comment | Organism |
---|---|---|
Cu, Zn-superoxide dismutase | - |
Mus musculus |
SOD1 | - |
Mus musculus |
Organism | Comment | Expression |
---|---|---|
Mus musculus | 2-[(3-iodophenyl)methylsulfanyl]-5-pyridin-4-yl-1,3,4-oxadiazole, a known protein kinase inhibitor, decreases enzyme mutant G93A-SOD1 expression in vitro and in the brain and spinal cord in vivo. Compounds 3-[1-(3-hydroxypropyl)-1H-pyrrolo[2,3-b]pyridin-3-yl]-4-(pyrazin-2-yl)-1H-pyrrole-2,5-dione, 2-chloro-1-(4,5-dibromothiophen-2-yl)ethan-1-one, 2-bromo-1-(4-bromophenyl)ethan-1-one, 4-(5-[[(3-iodophenyl)methyl]sulfanyl]-1,3,4-oxadiazol-2-yl)pyridine, 4-(5-[[(3-methoxyphenyl)methyl]sulfanyl]-1,3,4-oxadiazol-2-yl)pyridine, 4-(5-[[(3-fluorophenyl)methyl]sulfanyl]-1,3,4-oxadiazol-2-yl)pyridine, 4-[5-([[4-(trifluoromethyl)phenyl]methyl]sulfanyl)-1,3,4-oxadiazol-2-yl]pyridine, 4-(5-[[(3-chlorophenyl)methyl]sulfanyl]-1,3,4-oxadiazol-2-yl)pyridine, 4-(5-[[(3-nitrophenyl)methyl]sulfanyl]-1,3,4-oxadiazol-2-yl)pyridine, 4-(5-[[(3-bromophenyl)methyl]sulfanyl]-1,3,4-oxadiazol-2-yl)pyridine, 4-(5-[[(4-methoxyphenyl)methyl]sulfanyl]-1,3,4-oxadiazol-2-yl)pyridine, 4-(5-[[(4-chlorophenyl)methyl]sulfanyl]-1,3,4-oxadiazol-2-yl)pyridine, 4-(5-[[(4-bromophenyl)methyl]sulfanyl]-1,3,4-oxadiazol-2-yl)pyridine, 4-(5-[[(4-iodophenyl)methyl]sulfanyl]-1,3,4-oxadiazol-2-yl)pyridine, 4-(5-[[(4-fluorophenyl)methyl]sulfanyl]-1,3,4-oxadiazol-2-yl)pyridine, 4-(5-[[(4-methylphenyl)methyl]sulfanyl]-1,3,4-oxadiazol-2-yl)pyridine, 4-(5-[[(4-nitrophenyl)methyl]sulfanyl]-1,3,4-oxadiazol-2-yl)pyridine, 4-(5-[[(4-nitrophenyl)methyl]sulfanyl]-1,3,4-oxadiazol-2-yl)pyridine suppress the enzyme expression | down |
Mus musculus | GSK3B-IX and aloisine-A induce the enzyme expression | up |
General Information | Comment | Organism |
---|---|---|
malfunction | mutation of Cu,Zn-superoxide dismutase (SOD1) is responsible for genetically linked autosomal dominant neurodegenerative disease, amyotrophic lateral sclerosis (ALS) in humans | Mus musculus |