Description

MK-8245 is a liver-targeted inhibitor of stearoyl-CoA desaturase (SCD; IC₅₀s = 3, 3, and 1 nM for rat, mouse, and human SCD1, respectively). It is selective for SCD1 over Δ⁵- and Δ⁶-desaturases (IC₅₀s = >100,000 nM). MK-8245 (20-60 mg/kg) reduces the hepatic, but not Harderian gland, ratio of oleic acid to stearic acid, a marker of chronic SCD activity, and blood glucose levels, without inducing the formation of skin lesions or eye squinting behavior, in a mouse model of high-fat diet-induced obesity. It also inhibits hepatitis C virus (HCV) replication without inducing cytotoxicity in LucNeo2 cells (IC₅₀ = 39.8 nM).

Uses

This product is Informer compound X9 of the Aryl Halide Chemistry Informer Library developed by chemists at Merck & Co., Inc., Kenilworth, NJ, U.S., which contains 18 drug-like molecules representative of those encountered in complex synthesis. By screening a new reaction against the Informer Library, chemists can directly compare and analyse a reaction′s successes and shortcomings among different methods and various research teams. It may also be used to facilitate deeper method development for performance or utility.

in vivo

target

SCD1 (human)

References

[1] oballa rm, belair l, black wc, bleasby k, chan cc, desroches c, du x, gordon r, guay j, guiral s, hafey mj, hamelin e, huang z, kennedy b, lachance n, landry f, li cs, mancini j, normandin d, pocai a, powell da, ramtohul yk, skorey k, srensen d, sturkenboom w, styhler a, waddleton dm, wang h, wong s, xu l, zhang l. development of a liver-targeted stearoyl-coa desaturase (scd) inhibitor (mk-8245) to establish a therapeutic window for the treatment of diabetes and dyslipidemia. j med chem. 2011 jul 28;54(14):5082-96.
[2] lachance n, guiral s, huang z, leclerc jp, li cs, oballa rm, ramtohul yk, wang h, wu j, zhang l. discovery of potent and liver-selective stearoyl-coa desaturase (scd) inhibitors in an acyclic linker series. bioorg med chem lett. 2012 jan 1;22(1):623-7.