The safety and efficacy of this agent(s), or use in this setting, has not been established or is subject to confirmation. For an agent(s) whose safety and efficacy has not been established or confirmed, future regulatory approval or commercial availability is not guaranteed.

Atirmociclib (PF-07220060)

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Molecule overview Clinical trials

Atirmociclib (PF-07220060)

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

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Overview + Rationale Mechanism of Action Stage of Development

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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

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

Atirmociclib is a selective CDK4 inhibitor with potential antineoplastic activity in several solid tumors
Atirmociclib inhibits the CDK4/cyclinD complex and renders the Rb/E2F transcription system inactive

Inhibition