Gil-Martinez, Jon; Macias, Iratxe; Unione, Luca; Bernardo-Seisdedos, Ganeko; Lopitz-Otsoa, Fernando; Fernandez-Ramos, David; Lain, Ana; Sanz-Parra, Arantza; Mato, Jose M.; Millet, Oscar published an article in 2021. The article was titled 《Therapeutic targeting of fumaryl acetoacetate hydrolase in hereditary tyrosinemia type I》, and you may find the article in International Journal of Molecular Sciences.Electric Literature of C7H5N The information in the text is summarized as follows:
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. The results came from multiple reactions, including the reaction of 4-Ethynylpyridine(cas: 2510-22-7Electric Literature of C7H5N)
4-Ethynylpyridine(cas: 2510-22-7) belongs to pyridine. Pyridine is very deactivated towards electrophilic substitution with respect to benzene. For this reason classical formylation, using methods such as the Gattermann or Vilsmeier reactions, are not generally successful. Electric Literature of C7H5N