Description
WH-4-23 (837422-57-8) is a potent and selective inhibitor of Src family kinases Lck and Src, IC50=2 and 6 nM respectively.1,2 Also inhibits SIK, IC50=10, 22 and 60 nM for SIK 1, 2 and 3 respectively.3 May be used along with PD-325901 and CHIR-99021 to support self-renewal of na?ve human embryonic stem cells.4
Uses
WH-4-023 is a potent and selective dual lymphocyte-specific kinase (Lck) inhibitor.
Definition
ChEBI: N-(2,4-dimethoxyphenyl)-N-[2-[4-(4-methyl-1-piperazinyl)anilino]-4-pyrimidinyl]carbamic acid (2,6-dimethylphenyl) ester is a member of piperazines.
Biochem/physiol Actions
WH-4-023 (KIN112) is a potent and selective inihbitor of the tyrosine kinases Lck and Src with IC50 values of 2 nM for Lck and 6 nM for Src. WH-4-023 is a somewhat less potent inhibitor of salt-inducible kinases (SIKs) with IC50 values of 10, 22 and 60 nM for SIK 1, 2 and 3 respectively. WH-4-023 was found to support self-renewal of naive human embryonic stem cells, in particular in combination with PD 0325901 (PZ0162), CHIR99021 (SML1046), and SB-590885 (SML0501).
References
Martin et al. (2006), Novel 2-aminopyrimidine carbamates as potent and orally active inhibitors of Lck: synthesis, SAR, and in vivo anti-inflammatory activity; J. Med. Chem., 49 4981
Moroco et al. (2015), A discovery Strategy for Selective Inhibitors of c-Src in Complex with the Focal Adhesion Kinase SH3/SH2-binding Region; Chem. Biol. Drug. Des., 86 144
Clark et al. (2012), Phosphorylation of CRTC3 by the salt-inducible kinases controls the interconversion of classically activated and regulatory macrophages; Proc. Natl. Acad. Sci. USA, 109 16986
Theunissen et al. (2014), Systemic identification of culture conditions for introduction and maintenance of na?ve human pluripotency; Cell Stem Cell, 15 471
