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Atirmociclib (PF-07220060)

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Molecule overview Clinical trials Scientific presentations

Atirmociclib (PF-07220060)

Atirmociclib | PF-07220060 is an investigational compound. Its safety and efficacy have not been established.

Overview + Rationale Mechanism of Action Stage of Development

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Overview + Rationale

RATIONALE FOR CANCER TARGET^1-3

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 subsequent E2F-mediated transcription are required for G1 cell-cycle progression
Aberrations in the cell-cycle have been implicated in human cancer pathogenesis

OVERVIEW²

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.