Preferred Label : CK1alpha/CDK7/CDK9 Inhibitor BTX-A51;
NCIt definition : The ditosylated salt of A51, an orally bioavailable inhibitor of casein kinase 1alpha
(CK1alpha) and cyclin-dependent kinases 7 and 9 (CDK7 and CDK9), with potential antineoplastic
activity. Upon administration, BTX-A51 binds to and inhibits the activity of CK1alpha,
CDK7, and CDK9. Blocking the phosphorylation and kinase activity of CK1alpha prevents
the enhanced binding of murine double minute X (MDMX) to p53, the formation of CK1alpha
and MDM2 complex, and the resulting inhibition of p53. This induces p53-mediated cell
cycle arrest, slowing tumor cell proliferation. Blocking the phosphorylation and kinase
activity of CDK7 and CDK9 prevents the positive transcription elongation factor b
(PTEFb)-mediated activation of RNA polymerase II (RNA Pol II) and leads to the inhibition
of gene transcription of various anti-apoptotic proteins. This also induces cell cycle
arrest and apoptosis, slowing tumor cell proliferation. CK1alpha, a serine/threonine
kinase and a leukemic stem cell target, acts as a tumor suppressor in several cancers
through the negative regulation of Wnt/beta-catenin signaling and p53. It negatively
regulates p53 by phosphorylating MDMX, thus enhancing binding of MDMX to p53, as well
as by forming a complex with MDM2. CDK7, a serine/threonine kinase, plays a role in
controlling cell cycle progression, transcriptional regulation, and promotes the expression
of key oncogenes such as c-Myc through the phosphorylation of RNA Pol II. CDK9, also
a serine/threonine kinase, regulates elongation of transcription through phosphorylation
of RNA Pol II at serine 2 (p-Ser2-RNAPII). It is upregulated in various tumor cell
types and plays a key role in the regulation of RNA Pol II-mediated transcription
of anti-apoptotic proteins. Tumor cells are dependent on anti-apoptotic proteins for
their survival.;
Molecule name : BTX A51; BTX-A51;
NCI Metathesaurus CUI : CL1378832;
Origin ID : C169027;
UMLS CUI : C5239320;
Semantic type(s)
- concept_is_in_subset
- has_target
