Gil-Martinez, Jon published the artcileTherapeutic targeting of fumaryl acetoacetate hydrolase in hereditary tyrosinemia type I, Safety of 3-Amino-4-methyl-N-(4-methyl-2-pyridyl)benzamide, the publication is International Journal of Molecular Sciences (2021), 22(4), 1789, database is CAplus and MEDLINE.
Fumarylacetoacetate hydrolase (FAH) is the fifth enzyme in the tyrosine catabolism pathway. A deficiency in human FAH leads to hereditary tyrosinemia type I (HT1), an autosomal recessive disorder that results in the accumulation of toxic metabolites such as succinylacetone, maleylacetoacetate, and fumarylacetoacetate in the liver and kidney, among other tissues. The disease is severe and, when untreated, it can lead to death. A low tyrosine diet combined with the herbicidal nitisinone constitutes the only available therapy, but this treatment is not devoid of secondary effects and long-term complications. In this study, we targeted FAH for the first-time to discover new chem. modulators that act as pharmacol. chaperones, directly associating with this enzyme. After screening several thousand compounds and subsequent chem. redesign, we found a set of reversible inhibitors that associate with FAH close to the active site and stabilize the (active) dimeric species, as demonstrated by NMR spectroscopy. Importantly, the inhibitors are also able to partially restore the normal phenotype in a newly developed cellular model of HT1.
International Journal of Molecular Sciences published new progress about 1019398-93-6. 1019398-93-6 belongs to amides-buliding-blocks, auxiliary class Pyridine,Amine,Benzene,Amide, name is 3-Amino-4-methyl-N-(4-methyl-2-pyridyl)benzamide, and the molecular formula is C14H15N3O, Safety of 3-Amino-4-methyl-N-(4-methyl-2-pyridyl)benzamide.
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