Dinaciclib (SCH727965)

Cas No.:	779353-01-4
Chemical Name:	2-[(2S)-1-[3-ethyl-7-[(1-oxidopyridin-1-ium-3-yl)methylamino]pyrazolo[1,5-a]pyrimidin-5-yl]piperidin-2-yl]ethanol
Synonyms:	SCH 727965; SCH727965; SCH-727965
SMILES:	OCC[C@H]1N(C2=NC3=C(CC)C=NN3C(NCC4=C[N+]([O-])=CC=C4)=C2)CCCC1
Formula:	C21H28N6O2
M.Wt:	396.49
Purity:	>98%
Sotrage:	2 years -20°C Powder, 2 weeks 4°C in DMSO, 6 months -80°C in DMSO

Description:	Dinaciclib is a potent inhibitor of CDK, with IC50s of 1, 1, 3, and 4 nM for CDK2, CDK5, CDK1, and CDK9, respectively.
In Vivo:	Dinaciclib (8, 16, 32, and 48 mg/kg, i.p.) results in tumor inhibition by 70%, 70%, 89%, and 96%, respectively; Dinaciclib (SCH 727965) is well tolerated, and the maximum body weight loss in the highest dosage group is 5%. Dinaciclib has a short plasma half-life in mouse. A dose of 5 mg/kg Dinaciclib given i.p. in mice is associated with a plasma half-life of ~0.25 hour[1]. Treatment with Dinaciclib (SCH727965) given as twice weekly i.p. doses of 40 mg/kg for 4 weeks causes significant tumor growth inhibition (TGI) in 10/10 (100%) of low-passage subcutaneous pancreatic xenografts tested[2].
In Vitro:	Dinaciclib (SCH 727965) is a potent DNA replication inhibitor that blocks thymidine (dThd) DNA incorporation in A2780 cells with an IC50 of 4 nM. Dinaciclib (100 nM) inhibits phosphorylation of the retinoblastoma (Rb) tumor suppressor protein and induces accumulation of the p85 PARP caspase cleavage product[1]. In vitro cell growth of pancreatic cancer cells is inhibited by Dinaciclib (SCH727965) in a dose-dependent manner. Upon incubation with Dinaciclib for 72 h, the GI50s are approximately 10 and 20 nM for MIAPaCa-2 and Pa20C cells, respectively. These results are consistent with studies of Dinaciclib in other cancer cell lines. In soft agar assays, 5 to 10 nM of Dinaciclib significantly reduces colony formation and anchorage independent growth of MIAPaCa-2 cells. Moreover, in vitro cell migration of Pa20C and MIAPaCa-2 cells is significantly reduced by Dinaciclib-concentrations starting from 2-5 nM, as demonstrated using BD FluoroChrom, modified Boyden Chamber and wound healing assays[2].