CDK4 Inhibitor
PF-07220060 is an investigational compound. Its safety and efficacy have not been established.
Overview + Rationale
Rationale for a Cancer Target
- Cyclin-dependent kinases (CDKs) play important roles in the control of cell division and modulate transcription in response to several extra and intracellular cues.
- The cyclin D–CDK4/6–retinoblastoma (Rb) pathway plays a key role in the G1 phase of the cell cycle. Phosphorylation of Rb and subsequentE2F-mediated transcription are required for G1 cell-cycle progression.
- Aberrations in the cell-cycle have been implicated in human cancer pathogenesis.
![](/sites/default/files/2024-05/CDK4%20Rationale.jpg)
The Rb tumor suppressor protein plays a pivotal role in the negative control of the cell cycle. It is responsible for a major G1 checkpoint, blocking S -phase entry and cell growth. Phosphorylation leads to functional inactivation of Rb. Loss of Rb cell cycle –suppressive functions can be mediated through multiple mechanisms: loss of Rb, increased signaling through CDK4 & 6 amplification, overexpression or aberration of cyclin D/E, and loss of the inhibitory function of gene products, such as CDKN2A/B the latter leading to CDK4/6 activity.
Mechanism of Action
- PF-07220060 is a selective CDK4 inhibitor with potential antineoplastic activity in several solid tumors
- PF-07220060 inhibits the CDK4/cyclinD complex and renders the Rb/E2F transcription system inactive
Inhibition
![](/sites/default/files/2024-05/CDK4%20Mechanism.jpg)
Stage of Development
Phase 1b/2 Combination
(1L) Phase 1/2A Monotherapy and Combination
(2L) Phase 3 Combination