On December 23, 2021, Come, Jon H.; Senter, Timothy J.; Clark, Michael P.; Court, John J.; Gale-Day, Zachary; Gu, Wenxin; Krueger, Elaine; Liang, Jianglin; Morris, Mark; Nanthakumar, Suganthini; O′Dowd, Hardwin; Maltais, Francois; Iyer, Ganesh; Andreassi, John; Boucher, Christina; Considine, Tony; Moody, Cameron S.; Taylor, William; Mohanty, Arun K.; Huang, Yulin; Zuccola, Harmon; Coll, Joyce; Bonanno, Kenneth C.; Gagnon, Kevin J.; Gan, Lu; Lu, Fan; Gao, Hong; Chakilam, Ananthisrinivas; Engtrakul, Juntyma; Song, Bin; Crawford, Dan; Doyle, Elisabeth; Kramer, Tal; Vought, Bryan; Phillips, Jonathan; Kemper, Raymond; Sanders, Martin; Swett, Rebecca; Furey, Brinley; Winquist, Ray; Bunnage, Mark E.; Jackson, Katrina L.; Charifson, Paul S.; Magavi, Sanjay S. published an article.Category: thiazole The title of the article was Discovery and Optimization of Pyrazole Amides as Inhibitors of ELOVL1. And the article contained the following:
Accumulation of very long chain fatty acids (VLCFAs) due to defects in ATP binding cassette protein D1 (ABCD1) is thought to underlie the pathologies observed in adrenoleukodystrophy (ALD). Pursuing a substrate reduction approach based on the inhibition of elongation of very long chain fatty acid 1 enzyme (ELOVL1), we explored a series of thiazole amides that evolved into compound 27-a highly potent, central nervous system (CNS)-penetrant compound with favorable in vivo pharmacokinetics. Compound 27 (I) selectively inhibits ELOVL1, reducing C26:0 VLCFA synthesis in ALD patient fibroblasts, lymphocytes, and microglia. In mouse models of ALD, compound 27 treatment reduced C26:0 VLCFA concentrations to near-wild-type levels in blood and up to 65% in the brain, a disease-relevant tissue. Preclin. safety findings in the skin, eye, and CNS precluded progression; the origin and relevance of these findings require further study. ELOVL1 inhibition is an effective approach for normalizing VLCFAs in models of ALD. The experimental process involved the reaction of 4-Phenylthiazol-2-amine(cas: 2010-06-2).Category: thiazole
The Article related to elovl1 inhibitor vlcfa adrenoleukodystrophy, Placeholder for records without volume info and other aspects.Category: thiazole
Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica