Dinaciclib

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

一种有效的选择性 CDK 抑制剂，针对 CDK2、CDK5、CDK1 和 CDK9 的 IC50 分别为 1、1、3 和 4 nM。

A potent and selective CDK inhibitor with IC50 of 1, 1, 3 and 4 nM against CDK2, CDK5, CDK1 and CDK9, respectively; completely suppresses Rb phosphorylation and inhibits bromodeoxyuridine incorporation in >100 tumor cell lines; exhibits superior activity with an improved therapeutic index compared with flavopiridol.Blood Cancer Phase 3 Clinical(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. 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.(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. 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.

——

——

SCH 727965 | SCH727965 | SCH-727965

Cell Cycle/DNA Damage

CDK

CDK1|CDK2|CDK5|CDK9

Cancer

Blood cancer

779353-01-4

396.486

C21H28N6O2

>98% (HPLC)

DMSO: ≥ 56 mg/mL

OCC[C@H]1N(C2=NC3=C(CC)C=NN3C(NCC4=C[N+]([O-])=CC=C4)=C2)CCCC1

2-Piperidineethanol, 1-[3-ethyl-7-[[(1-oxido-3-pyridinyl)methyl]amino]pyrazolo[1,5-a]pyrimidin-5-yl]-, (2S)-

(-20℃)

With Ice Pack

≥ 2 years