Definition

An orally bioavailable, selective inhibitor of cyclin-dependent kinase 7 (CDK7), with potential antineoplastic activity. Upon oral administration, CDK7 inhibitor XL102 selectively targets, covalently binds to and inhibits the activity of CDK7, thereby inhibiting CDK7-mediated signaling. The inhibition of CDK7 prevents phosphorylation of the carboxy-terminal domain (CTD) of RNA polymerase II, thereby preventing transcription of important cancer-promoting genes. It prevents phosphorylation of the cell cycle kinases CDK1, 2, 4, and 6, thereby disrupting uncontrolled cell cycle progression. Altogether, this may induce apoptosis, cause cell cycle arrest, inhibit DNA damage repair and inhibit tumor cell proliferation in certain cancers that are dependent on CDK7-mediated transcriptional regulation and signaling. CDK7, a serine/threonine kinase, plays a role in controlling cell cycle progression, transcriptional regulation, and promotes the expression of key oncogenes through the phosphorylation of RNA polymerase II. It’s overexpressed in multiple cancers.