CDK8/CDK19 inhibitor, highly potent, selective and orally available
Sample solution is provided at 25 µL, 10mM.
Publications citing ApexBio Products
|Cas No.||1449228-40-3||SDF||Download SDF|
|Solubility||Soluble in DMSO||Storage||Store at -20°C|
Senexin B is a highly potent, selective and orally available CDK8/CDK19 inhibitor with IC50 values ranging from 24-50 nM .
Cyclin-dependent kinase 8 (CDK8), along with its closely related isoform CDK19, is an oncogenic transcription-regulating kinase. CDK8 plays an essential role in the pluripotent stem cell phenotype. Also, CDK8 is a regulator of several transcriptional programs involved in carcinogenesis and has been identified as an oncogene in melanoma and colon cancer .
Senexin B is a highly potent, selective and orally available CDK8/CDK19 inhibitor. Senexin B exhibited selectivity for CDK8 and CDK19 with Kd values of 140 nM and 80 nM. Senexin B was fully soluble in 20% propylene glycol at 1 mM, and fully soluble in water at 50 mM concentration. Senexin B inhibited CDK8/19 in low nanomolar range in vitro and in vivo in an ATP competitive manner . In HT1080 cells, Senexin B inhibited CMV-GFP expression induced by IPTG-inducible p21 .
In CB-17 SCID mice (8 weeks old), i.p. injections of Senexin B (40 mg/kg) or carrier for 5 days, mice were then injected s.c. with 1 x 106 cells of human A549 lung cancer cell line, Senexin B significantly slowed tumor growth. In female nude mice with the fat pad injected orthotopically with MDA-MB-468 triple-negative breast cancer (TNBC) cells, 5-day pretreatment with 25 mg/kg daily doses of Senexin B (i.p.) produced strong and sustained inhibition of tumor growth .
1. Cdk8/cdk19 selective inhibitors and their use in anti-metastatic and chemopreventative methods for cancer. Publication number: WO2013116786 A1.
2. Donald C. Porter, Mengqian Chen, Jiaxin Liang, et al. Abstract PR08: Targeting tumor microenvironment with selective small-molecule inhibitors of CDK8/19.