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 nave 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
[1] MATTHEW W. MARTIN. Novel 2-Aminopyrimidine Carbamates as Potent and Orally Active Inhibitors of Lck: Synthesis, SAR, and in Vivo Antiinflammatory Activity[J]. Journal of Medicinal Chemistry, 2006, 49 16: 4981-4991. DOI:
10.1021/jm060435i[2] JAMIE A. MOROCO. A Discovery Strategy for Selective Inhibitors of c-Src in Complex with the Focal Adhesion Kinase SH3/SH2-binding Region[J]. Chemical Biology & Drug Design, 2014, 86 2: 144-155. DOI:
10.1111/cbdd.12473[3] KRISTOPHER CLARK. Phosphorylation of CRTC3 by the salt-inducible kinases controls the interconversion of classically activated and regulatory macrophages.[J]. Proceedings of the National Academy of Sciences of the United States of America, 2012: 16986-16991. DOI:
10.1073/pnas.1215450109[4] Systemic identification of culture conditions for introduction and maintenance of naïve human pluripotency
