Chemistry is the science of change. But why do chemical reactions take place? Why do chemicals react with each other? The answer is in thermodynamics and kinetics.In a document type is Article, the author is Finlay, M. Raymond V. and a compound is mentioned, 1120-95-2, 3-Chloropyridazine, introducing its new discovery. 1120-95-2
Discovery of a thiadiazole-pyridazine-based allosteric glutaminase 1 inhibitor series that demonstrates oral bioavailability and activity in tumor xenograft models
Tumors have evolved a variety of methods to reprogram conventional metabolic pathways to favor their own nutritional needs, including glutaminolysis, the first step of which is the hydrolysis of glutamine to glutamate by the amidohydrolase glutaminase 1 (GLS1). A GLS1 inhibitor could potentially target certain cancers by blocking the tumor cell’s ability to produce glutamine-derived nutrients. Starting from the known GLS1 inhibitor bis-2-(5-phenylacetamido-1,2,4-thiadiazol-2-yl)ethyl sulfide, we describe the medicinal chemistry evolution of a series from lipophilic inhibitors with suboptimal physicochemical and pharmacokinetic properties to cell potent examples with reduced molecular weight and lipophilicity, leading to compounds with greatly improved oral exposure that demonstrate in vivo target engagement accompanied by activity in relevant disease models.
Interested yet? Keep reading other articles of 53558-93-3!, 1120-95-2
Reference£º
Pyridazine – Wikipedia,
Pyridazine | C4H4N413 – PubChem