1421693-22-2

中文名称 CS-2259

英文名称 CDKI-73

CAS 1421693-22-2

分子式 C15H15FN6O2S2

分子量 394.45

MOL 文件 1421693-22-2.mol

更新日期 2024/11/27 15:14:11

1421693-22-2 结构式

基本信息物理化学性质常见问题列表

基本信息

中文别名

化合物CDKI-73

英文别名

CS-2259
CDKI-73
CDKI-73 (CDKI73)
Benzenesulfonamide, 3-[[5-fluoro-4-[4-methyl-2-(methylamino)-5-thiazolyl]-2-pyrimidinyl]amino]-

所属类别

生物化工：激动剂抑制剂

物理化学性质

沸点642.9±65.0 °C(Predicted)

密度1.524±0.06 g/cm3(Predicted)

储存条件-20°C储存

溶解度DMSO:52.0(Max Conc. mg/mL);131.83(Max Conc. mM)

酸度系数(pKa)10.06±0.60(Predicted)

形态Solid

颜色Light yellow to yellow

常见问题列表

生物活性

CDKI-73 (LS-007) 是一种有效的 CDK 抑制剂，对CDK1、CDK2、CDK4和CDK9的IC50值分别为8.17 nM，3.27 nM，8.18 nM和5.78 nM。CDKI-73 可诱导癌细胞的凋亡。CDKI-73 是一种口服生物利用型且高效的 CDK9 抑制剂，可用于治疗急性髓细胞性白血病。

靶点

Target	Value
CDK2 (Cell-free assay)	3.27 nM
CDK9 (Cell-free assay)	5.78 nM
CDK1 (Cell-free assay)	8.17 nM
CDK4 (Cell-free assay)	8.18 nM

体外研究

CDKI-73 is highly cytotoxic to primary leukemia cells derived from CLL patients (mean LD ₅₀ = 0.08 μM) and shows>500-fold selectivity for primary leukemia cells over normal B-lymphocytes (LD ₅₀ = 40.5 μM).
CDKI-73 (0.1 μM, 4 h) inhibits the phosphorylation of serine 2 of RNA polymerase II and MCL1 protein expression in CLL cells.
CDKI-73 induced caspase-dependent apoptosis that was preceded by dephosphorylation of cdk9 and serine 2 of RNA polymerase II.
CDKI-73 is highly effective against all cell lines tested with an IC ₅₀ 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 IC ₅₀ 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.

体内研究

CDKI-73 (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 C _max 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. Its oral bioavailability (F) ranged from 54 to 85% across the three doses.