Delpire, Eric; Days, Emily; Lewis, L. Michelle; Mi, Dehui; Kim, Kwangho; Lindsley, Craig W.; Weaver, C. David published the artcile< Small-molecule screen identifies inhibitors of the neuronal K-Cl cotransporter KCC2>, Product Details of C6H8N2S, the main research area is potassium chlorine cotransporter KCC2 inhibitor preparation drug screening.
KCC2, a neuronal-specific K-Cl co-transporter, plays a major role in maintaining intracellular Cl- concentration in neurons below its electrochem. equilibrium potential, thus favoring robust GABA hyperpolarizing or inhibitory responses. The pharmacol. of the K-Cl co-transporter is dominated by loop diuretics such as furosemide and bumetanide, mols. used in clin. medicine because they inhibit the loop of Henle Na-K-2Cl co-transporter with much higher affinity. To identify mols. that affect KCC2 activity, the authors developed a fluorescence-based assay suitable for high-throughput screening (HTS) and used the assay to screen a library of 234,000 small mols. They identified a large number of mols. that either decrease or increase the activity of the co-transporter. Here, they report the characterization of a small number of inhibitors, some of which inhibit KCC2 activity in the submicromolar range without substantially affecting NKCC1 activity. Using medicinal chem., they synthesized a number of variants, tested their effect on KCC2 function, and provide an anal. of structure/activity relationships. They also used one of the compounds to demonstrate competitive inhibition in regard to external [K+] vs. non-competitive inhibition in respect to external [Cl-].
Proceedings of the National Academy of Sciences of the United States of America published new progress about Carrier-mediated biological transport. 324579-90-0 belongs to class thiazole, and the molecular formula is C6H8N2S, Product Details of C6H8N2S.
Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica