Cyclin-dependent kinases (CDKs) are critical positive regulators of cell cycle progression and cellular transcription whose dysregulation can lead to the development of cancer. Dinaciclib inhibits CDK1, CDK2, CDK5, and CDK9 activity in vitro with IC50 values of 3, 1, 1, and 4 nM, respectively. Compared to the pan-CDK inhibitor flavopiridol, dinaciclib is an equally potent inhibitor of CDK1 and CDK9 but a 12-14-fold more potent inhibitor of CDK2 and CDK5. It has been shown to inhibit DNA synthesis by blocking thymidine incorporation in A2780 ovarian cancer cells with an IC50 value of 4nM. At 5mg/kg it prevents tumor growth by 50% in an A2780 ovarian carcinoma mouse xenograft model and is active against a broad spectrum of human tumor cell lines in vitro (IC50s = 7-17nM).
Solubility:~0.5mg/ml in a 1:1 solution of DMF:PBS (pH 7.2); ~25mg/ml in EtOH & DMF; ~15mg/ml
Storage and Stability:Lyophilized powder may be stored at -20°C. Stable for 12 months at -20°C. Reconstitute with DMSO, ethanol or dimethyl formamide. Store at -20°C. For maximum recovery of product, centrifuge the original vial after thawing and prior to removing the cap.
