837422-57-8 Usage
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.
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
Check Digit Verification of cas no
The CAS Registry Mumber 837422-57-8 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 8,3,7,4,2 and 2 respectively; the second part has 2 digits, 5 and 7 respectively.
Calculate Digit Verification of CAS Registry Number 837422-57:
(8*8)+(7*3)+(6*7)+(5*4)+(4*2)+(3*2)+(2*5)+(1*7)=178
178 % 10 = 8
So 837422-57-8 is a valid CAS Registry Number.
837422-57-8Relevant articles and documents
Novel 2-aminopyrimidine carbamates as potent and orally active inhibitors of Lck: Synthesis, SAR, and in vivo antiinflammatory activity
Martin, Matthew W.,Newcomb, John,Nunes, Joseph J.,McGowan, David C.,Armistead, David M.,Boucher, Christina,Buchanan, John L.,Buckner, William,Chai, Lilly,Elbaum, Daniel,Epstein, Linda F.,Faust, Theodore,Flynn, Shaun,Gallant, Paul,Gore, Anu,Gu, Yan,Hsieh, Faye,Huang, Xin,Lee, Josie H.,Metz, Daniela,Middleton, Scot,Mohn, Deanna,Morgenstern, Kurt,Morrison, Michael J.,Novak, Perry M.,Oliveira-Dos-Santos, Antonio,Powers, David,Rose, Paul,Schneider, Stephen,Sell, Stephanie,Tudor, Yanyan,Turci, Susan M.,Welcher, Andrew A.,White, Ryan D.,Zack, Debra,Zhao, Huilin,Zhu, Li,Zhu, Xiaotian,Ghiron, Chiara,Amouzegh, Patricia,Ermann, Monika,Jenkins, James,Johnston, David,Napier, Spencer,Power, Eoin
, p. 4981 - 4991 (2007/10/03)
The lymphocyte-specific kinase (Lck) is a cytoplasmic tyrosine kinase of the Src family expressed in T cells and NK cells. Genetic evidence in both mice and humans demonstrates that Lck kinase activity is critical for signaling mediated by the T cell receptor (TCR), which leads to normal T cell development and activation. A small molecule inhibitor of Lck is expected to be useful in the treatment of T cell-mediated autoimmune and inflammatory disorders and/or organ transplant rejection. In this paper, we describe the synthesis, structure-activity relationships, and pharmacological characterization of 2-aminopyrimidine carbamates, a new class of compounds with potent and selective inhibition of Lck. The most promising compound of this series, 2,6-dimethylphenyl 2-((3,5-bis(methyloxy)-4-((3-(4-methyl-1-piperazinyl)propyl)- oxy)phenyl)amino)-4-pyrimidinyl(2,4-bis(methyloxy)phenyl)carbamate (43) exhibits good activity when evaluated in in vitro assays and in an in vivo model of T cell activation.
