Disease relevance of PD 0332991

• PD 0332991, therefore, represents the first promising and specific inhibitor for therapeutic targeting of Cdk4/6 in multiple myeloma and possibly other B-cell cancers [1].
• PD 0332991 warrants phase II testing at 125 mg once daily, at which dose neutropenia was the sole significant toxicity [2].
• In this article, we review the development of palbociclib and its use in treatment of hormone receptor-positive metastatic breast cancer in the context of other FDA-approved agents in this setting [3].

High impact information on PD 0332991

• Inhibition of Cdk4/6 by PD 0332991 is not accompanied by induction of apoptosis [1].
• Here, we show that by specific inhibition of Cdk4/6, the orally active small-molecule PD 0332991 potently induces G(1) arrest in primary bone marrow myeloma cells ex vivo and prevents tumor growth in disseminated human myeloma xenografts [1].
• C2C12 myoblasts maintained in mitogen-rich media and exposed to a Cdk4/Cdk6 inhibitor PD 0332991 accumulated in G(1) cell cycle phase [4].
• Consistent with a role for Cdk4/Cdk6 activity as a regulator of myogenic differentiation, we observed that PD 0332991 exposure promoted morphologic changes and enhanced the expression of muscle-specific proteins in cultured myoblasts and in the Rh30 cell line [4].

Biological context of PD 0332991

• PD 0332991 is a highly specific inhibitor of cyclin-dependent kinase 4 (Cdk4) (IC50, 0.011 micromol/L) and Cdk6 (IC50, 0.016 micromol/L), having no activity against a panel of 36 additional protein kinases [5].

Analytical, diagnostic and therapeutic context of PD 0332991

• Oral administration of PD 0332991 to mice bearing the Colo-205 human colon carcinoma produces marked tumor regression [5].

References