Palbociclib (PD0332991)

Potent and selective inhibitor of Cdk4, IC50 = 11 nM and Cdk6, IC50 = 16 nM [1]. Inhibits phosphorylation of Rb protein and cell cycle progression through G1 in primary 5T33MM cells and sensitized these cells to killing by a proteasome inhibitor (bortezomib) in mouse models [2]. Induces autophagy and senescence in AGS gastric cancer cells [3]. Clinically useful breast cancer agent [4]. Cell cycle inhibitors boost tumor immunogenicity [5].

References:

1) El-Rayes et al. (2004), Cyclooxygenase-2-dependent and –independent effects of celecoxib in pancreatic cancer cell lines;  Mol. Cancer Ther., 3 1427

2) Menu et al. (2008), A novel therapeutic combination using PD 0332991 and bortezomib: study in 5T33MM myeloma model;  Cancer Res., 68 5519

3) Valenzuela et al. (2017), Palbociclib-induced autophagy and senescence in gastric cancer cells; Exp. Cell Res., 360 390

4) Palanisamy et al. (2016), Palbociclib: A new hope in the treatment of breast cancer;  J. Cancer Res. Ther., 12 1220

5) Minton et al. (2017) Tumour immunology: Cell cycle inhibitors boost tumour immunogenicity; Nat. Rev. Immunol., 17 529