Stearoyl-CoA desaturase (SCD) catalyzes the committed step of the conversion of saturated, long-chain fatty acids to monounsaturated fatty acids. The SCD1 gene is thought to play a key role in lipid homeostasis and body weight regulation.1,2,3 Thus, modulating SCD1 activity pharmacologically may be a useful tool for regulating type 2 diabetes, dyslipidemia, and obesity. CAY10566 is a potent and selective inhibitor of SCD1 that demonstrates IC50 values of 4.5 and 26 nM in mouse and human enzymatic assays, respectively.4 This compound inhibits the conversion of saturated, long-chain fatty acyl-CoAs to monounsaturated, long-chain fatty acyl-CoAs in Hep-G2 cells with IC50 values of 7.9 and 6.8 nM, respectively, when heptadecanoic acid and palmitic acid are used as the substrate.4
1
Cohen, P., Miyazaki, M., Socci, N.D., et al. Role for stearoyl-CoA desaturase-1 in leptin-mediated weight loss. Science297240-243(2002).
2
Dobrzyn, P., Sampath, H., Dobrzyn, A., et al. Loss of stearoyl-CoA desaturase 1 inhibits fatty acid oxidation and increases glucose utilization in the heart. Am J Physiol Endocrinol Metab294E357-E364(2008).
3
Miyazaki, M., Flowers, M.T., Sampath, H., et al. Hepatic stearoyl-CoA desaturase-1 deficiency protects mice from carbohydrate-induced adiposity and hepatic steatosis. Cell Metab6484-496(2007).
4
Liu, G., Lynch, J.K., Freeman, J., et al. Discovery of potent, selective, orally bioavailable stearoyl-CoA desaturase 1 inhibitors. J Med Chem503086-3100(2007).
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SMILES
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Cc1nnc(o1)c1ccc(nn1)N1CCC(CC1)Oc1cc(F)ccc1Cl
Background Reading
Miyazaki, M., Flowers, M.T., Sampath, H., et al. Hepatic stearoyl-CoA desaturase-1 deficiency protects mice from carbohydrate-induced adiposity and hepatic steatosis. Cell Metab6484-496(2007).
Dobrzyn, P., Sampath, H., Dobrzyn, A., et al. Loss of stearoyl-CoA desaturase 1 inhibits fatty acid oxidation and increases glucose utilization in the heart. Am J Physiol Endocrinol Metab294E357-E364(2008).
Cohen, P., Miyazaki, M., Socci, N.D., et al. Role for stearoyl-CoA desaturase-1 in leptin-mediated weight loss. Science297240-243(2002).
Liu, G., Lynch, J.K., Freeman, J., et al. Discovery of potent, selective, orally bioavailable stearoyl-CoA desaturase 1 inhibitors. J Med Chem503086-3100(2007).