CDKI-73

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

CDKI-73 是一种有效的 CDK9 抑制剂，Ki 为 4 nM，对广泛的 CLL 样品具有细胞毒性，平均 LD50 为 80 nM。

CDKI-73 is a potent CDK9 inhibitor with Ki of 4 nM, shows cytotoxicity against a broad CLL samples with mean LD50 of 80 nM; induces caspase-dependent apoptosis that was preceded by dephosphorylation of CDK9 and serine 2 of RNA polymerase II; CDKI-73 is more potent than the pan-CDK inhibitor Flavopiridol and shows >200-fold selectivity against primary leukemia cells when compared with normal CD34+ cells; shows cytotoxic synergy with the nucleoside analog fludarabine in in poor prognostic sub-groups of leukemia patients, which is associated with CDKI-73-mediated transcriptional inhibition of MCL1 and XIAP.

Asnuciclib is highly cytotoxic to primary leukemia cells derived from CLL patients (mean LD50 = 0.08 μM) and shows>500-fold selectivity for primary leukemia cells over normal B-lymphocytes (LD50=40.5 μM).Asnuciclib (0.1 μM, 4 h) inhibits the phosphorylation of serine 2 of RNA polymerase II and MCL1 protein expression in CLL cells.Asnuciclib induced caspase-dependent apoptosis that was preceded by dephosphorylation of cdk9 and serine 2 of RNA polymerase II.Asnuciclib is highly effective against all cell lines tested with an IC50 in the range of 0.012-0.517 μM; in particular three MLL-AML cell lines, namely MOLM13, MV4-11 and THP-1, were highly sensitive to CDKI-73 with IC50 values <0.062 μM. Cell Viability Assay.Cell Line:CLL cells.Concentration:0-1 μM.Incubation Time:48 h.Result:Shows preferential cytotoxicity in CLL cells.

Asnuciclib (25, 50, 100 mg/kg) markedly decreases tumor growth in a dose-dependent manner and results in a prolongation of animal life span (P < 0.001) without causing body weight loss and other overt toxicities.. Animal Model:MV4-11 tumor bearing mice.Dosage:25 mg/kg.Administration:Orally once everyday for 33 days.Result:Caused a remarkable delay in tumor growth compared to vehicle-treated mice, as reflected in a percentage for the mean tumor volume in treated to control mice of 43% at day 31.Animal Model:Balb/C mice aged 6-8 weeks.Dosage:2 mg/kg (IV), 10, 20 and 40 mg/kg (PO). (Pharmacokinetic Analysis.)Administration:IV and PO, single dose.Result:The Cmax increased from 1.29 to 3.66 μM at a mean time of 1 h and the area under the curve (AUC) of CDKI-73 increased from 3.51 to 12.8 μM.h when the oral dose was escalated from 10 to 40 mg/kg. CDKI-73 was eliminated from plasma with a mean terminal half-life (T1/2) of 2 h.

CDKI73

Angiogenesis

CDK

CDK

Cancer

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1421693-22-2

394.447

C15H15FN6O2S2

>98% (HPLC)

10 mM in DMSO

O=S(C1=CC=CC(NC2=NC=C(F)C(C3=C(C)N=C(NC)S3)=N2)=C1)(N)=O

Benzenesulfonamide, 3-[[5-fluoro-4-[4-methyl-2-(methylamino)-5-thiazolyl]-2-pyrimidinyl]amino]-

(-20℃)

With Ice Pack

≥ 2 years