Palbociclib | CDK4/CDK6 inhibitor

Palbociclib (571190-30-2) is a 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   Palbociclib is able to regulate the PRMT5-MDM4 axis leading to decreased MDM4 protein expression and subsequent p53 activation via CDK4 inhibition.⁶

References/Citations:

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) Goel et al. (2017), CDK4/6 inhibition triggers anti-tumour immunity; Nature 548 471
6)6) AbuHammad et al. (2019), Regulation of PRMT5-MDM4 axis is critical in the response to CDK4/6 inhibitors in melanoma; Proc. Natl. Acad. Sci. USA 116 179909