Lck/Src inhibitor,potent and selective
CAS：837422-57-8
分子式：C32H36N6O4
分子量：568.67
纯度：98%
存储：Store at -20°C

Background:

WH-4-023 is a potent and selective Lck and Src inhibitor with IC50 values of 2 and 6 nM, respectively [1]. It is also an inhibitor of IC50 values of 10, 22 and 60 nM for SIK 1, 2 and 3, respectively [2].

Lck and Src are cytoplasmic tyrosine kinases of the Src family expressed in T cells and NK cells [1]. SIKs restrict the formation of regulatory macrophages and that their inhibition greatly stimulates the production of IL-10 and other anti-inflammatory molecules [2].

WH-4-023 inhibited a number of protein tyrosine kinases that possess a Thr residue at the gatekeeper site, such as FGF and Ephrin receptors, Src family members (Src, Lck, and Yes) and BTK. WH-4-023 also inhibited the SIKs and did not inhibit any other member of the AMPK-related kinase subfamily, which all possess a large hydrophobic residue (Met or Leu) at the gatekeeper site. WH-4-023 inhibited SIK 1, 2 and 3 with IC50 values of 10, 22 and 60 nM, respectively. Also, WH-4-023 increased LPS-stimulated IL-10 production and greatly suppressed proinflammatory cytokine secretion [2].

参考文献:
[1].  Martin MW, Newcomb J, Nunes JJ, et al. Novel 2-aminopyrimidine carbamates as potent and orally active inhibitors of Lck: synthesis, SAR, and in vivo antiinflammatory activity. J Med Chem, 2006, 49(16): 4981-4991.
[2].  Clark K, MacKenzie KF, Petkevicius K, et al. Phosphorylation of CRTC3 by the salt-inducible kinases controls the interconversion of classically activated and regulatory macrophages. Proc Natl Acad Sci U S A, 2012, 109(42): 16986-16991.