BackCDK2 Inhibitor
PF-07104091 is an investigational compound. Its safety and efficacy have not been established.
Overview + Rationale
- The cyclin-dependent kinases (CDKs) are a family of enzymes that play a major role in controlling entry into the cell-cycle
- Treatments using CDK inhibition have focused on targeting cyclin-dependent kinases 4 and 6 (CDK4/6); however, primary and secondary resistance to CDK4/6 inhibition represent a challenge in the treatment of HR+ breast cancer
- CDK2 is another regulator of cell cycle progression that is activated by cyclins E and A, and also phosphorylates retinoblastoma (Rb)
- Copy number gains of cyclin E1 and E2 can be found in several tumor types and are associated with poorer prognosis in ovarian and endometrial cancer
- Besides Rb, CDK2 was shown to phosphorylate of a wide variety of target proteins, some of which are known to play a role in cancer pathogenesis
- CDK2 activity is largely dispensable for normal development in mice, but it is associated with tumor growth in multiple cancer types and emerging evidence suggests that selective CDK2 inhibition may provide a therapeutic benefit against certain tumor types
- PF-07104091 is a first in-class selective inhibitor under clinical investigation in patients with Hormone Receptor positive (HR+)/human epidermal growth factor receptor-2-negative (HER2-) breast cancer
Mechanism of Action
PF-07104091 selectively binds to, and inhibits the activity of CDK2 which may lead to cell cycle arrest through reduced phosphorylation of Rb, and other phosphotargets
Inhibition
Stage of Development
HR+/HER2- Metastatic Breast Cancer
Phase 1/2A Monotherapy and Combination*
Phase 1B/2 Combination*
Phase 1B/2 Combination*