CDK7 overexpression

Currently, trilaciclib, palbociclib, ribociclib, and abemaciclib that bear dual specificities against CDK4 and CDK6 have been approved for clinical usage, and more CDK4/6 targeted agents are actively under clinical evaluations, among which, TY-302, a novel CDK4/6 inhibitor being developed by TYK Medicines, is under Phase II trial (NCT04433494)...Several CDK7 targeted agents, such as SY-5609 and Samuraciclib (CT7001), are under development...# Shengli Dong and Apeng Liang contributed equally to this work. * Jun Li, Shengli Dong and Apeng Liang are the correspondent authors.

We show that CRPC cells, but not normal prostate cells, are addicted on the high activity of the key transcriptional kinases, CDK7 and CDK9.

In the dose-escalation stages (modified interval 3+3 design), a maximum tolerated (MTD) and/or recommended XL102 dose (RD) for use alone and in combination therapy with standard dose fulvestrant (HR+BC) or abiraterone/prednisone (mCRPC) will be established in independent strata. Accrual: The study began enrolling patients in February 2021 and is ongoing. Total enrollment estimated to be up to 298 subjects.

Therapeutically, we show that CDK7 knockdown with siRNA or selective inhibition with BS-181 decreases proliferation and induces apoptosis of osteosarcoma cells. This study supports CDK7 overexpression as an independent predictor of poor prognosis and promising therapeutic target for osteosarcoma.

TGN-1062 is a novel, selective, and reversible inhibitor of CDK7 and has significant antitumor activity in vivo. TGN-1062 is a potent CDK7 inhibitor with potential for clinical development.