PD 0332991-d₈

PD 0332991-d₈ is intended for use as an internal standard for the quantification of PD 0332991 (Item No. 16273) by GC- or LC-MS. PD 0332991 is an orally active, selective inhibitor of the cyclin D kinases Cdk4 (IC₅₀ = 11 nM) and Cdk6 (IC₅₀= 16 nM) with no activity against a panel of 36 additional protein kinases.¹ It has been reported to have antiproliferative activity against retinoblastoma-positive tumor cells, blocking retinoblastoma phosphorylation and inducing G₁ arrest at nanomolar concentrations. PD 0332991 can inhibit the growth of certain ER-positive or HER2-amplified breast cancer cells (IC₅₀s as low as 4 nM) and demonstrates synergy with tamoxifen (Item No. 13258) and trastuzumab, respectively.² PD 0332991 inhibition of Cdk4 activity has been used to demonstrate a role for insulin-activated cyclin D1-Cdk4 signaling in the control of glucose metabolism that is independent of cell cycle progression.³

WARNING This product is not for human or veterinary use.

1. Fry, D.W., Harvey, P.J., Keller, P.R., et al. Specific inhibition of cyclin-dependent kinase 4/6 by PD 0332991 and associated antitumor activity in human tumor xenografts. Mol. Cancer Ther. 3(11), 1427-1438 (2004).

2. Finn, R.S., Dering, J., Conklin, D., et al. PD 0332991, a selective cyclin D kinase 4/6 inhibitor, preferentially inhibits proliferation of luminal estrogen receptor-positive human breast cancer cell lines in vitro. Breast Cancer Res. 11(5), 1-13 (2009).

3. Lee, Y., Dominy, J.E., Choi, Y.J., et al. Cyclin D1-Cdk4 controls glucose metabolism independently of cell cycle progression. Nature 510(7506), 547-551 (2014).