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Literature summary for 1.15.1.1 extracted from

  • Lukas, T.J.; Schiltz, G.E.; Arrat, H.; Scheidt, K.; Siddique, T.
    Discovery of 1,3,4-oxidiazole scaffold compounds as inhibitors of superoxide dismutase expression (2014), Bioorg. Med. Chem. Lett., 24, 1532-1537 .
    View publication on PubMed

Protein Variants

Protein Variants Comment Organism
G93A site-directed mutagenesis Mus musculus

Inhibitors

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, structure–activity 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

Metals/Ions Comment Organism Structure
Cu2+ a Cu-ZnSOD Mus musculus
Zn2+ a Cu-ZnSOD 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
-
?

Organism

Organism UniProt Comment Textmining
Mus musculus
-
-
-

Source Tissue

Source Tissue Comment Organism Textmining
brain
-
Mus musculus
-
spinal cord
-
Mus musculus
-

Substrates and Products (Substrate)

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

Synonyms

Synonyms Comment Organism
Cu, Zn-superoxide dismutase
-
Mus musculus
SOD1
-
Mus musculus

Expression

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

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