CS-2259
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- CAS号:
- 1421693-22-2
- 英文名:
- CDKI-73
- 英文别名:
- CS-2259;CDKI-73;asnuciclib;CDKI-73
(CDKI73);3-((5-Fluoro-4-(4-methyl-2-(methylamino)thiazol-5-yl)pyrimidin-2-yl)amino)benzenesulfonamide;Benzenesulfonamide, 3-[[5-fluoro-4-[4-methyl-2-(methylamino)-5-thiazolyl]-2-pyrimidinyl]amino]-;toxicity,Inhibitor,low,AML,Acute,LS 007,myeloid,LS007,leukemia,CLL,Apoptosis,LS-007,endosome,Cyclin dependent kinase,CDKI73,CDKI-73,CDKI 73,inhibit,CDK
- 中文名:
- CS-2259
- 中文别名:
- 化合物CDKI-73;3-((5-氟-4-(4-甲基-2-(甲基氨基)噻唑-5-基)嘧啶-2-基)氨基)苯磺酰胺
- CBNumber:
- CB53034461
- 分子式:
- C15H15FN6O2S2
- 分子量:
- 394.45
- MOL File:
- 1421693-22-2.mol
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CS-2259化学性质
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沸点:
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642.9±65.0 °C(Predicted)
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密度:
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1.524±0.06 g/cm3(Predicted)
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储存条件:
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Store at -20°C
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溶解度:
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DMSO:52.0(Max Conc. mg/mL);131.83(Max Conc. mM)
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酸度系数(pKa):
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10.06±0.60(Predicted)
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CS-2259性质、用途与生产工艺
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。
| Target | Value |
CDK2
(Cell-free assay)
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3.27 nM
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CDK9
(Cell-free assay)
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5.78 nM
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CDK1
(Cell-free assay)
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8.17 nM
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CDK4
(Cell-free assay)
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8.18 nM
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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.
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Cell Line:
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CLL cells.
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Concentration:
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0-1 μM.
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Incubation Time:
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48 h.
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Result:
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Shows preferential cytotoxicity in CLL cells.
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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..
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Animal Model:
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MV4-11 tumor bearing mice.
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Dosage:
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25 mg/kg.
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Administration:
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Orally once everyday for 33 days.
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Result:
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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.
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Animal Model:
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Balb/C mice aged 6-8 weeks.
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Dosage:
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2 mg/kg (IV), 10, 20 and 40 mg/kg (PO). (Pharmacokinetic Analysis.)
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Administration:
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IV and PO, single dose.
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Result:
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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.
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CS-2259
上下游产品信息
上游原料
下游产品
| 更新日期 | 产品编号 | 产品名称 | CAS编号 | 包装 | 价格 |
|---|
| 2024/04/30 | HY-12445 | Asnuciclib | | 1 mg | 1600元 |
| 2024/04/30 | HY-12445 | CS-2259
CDKI-73 | 1421693-22-2 | 2mg | 2333元 |
1421693-22-2, CS-2259 相关搜索:
- 合成有机化合物配体
- 抑制剂
- 活性分子
- C15H15FN6O2S2
- 3-((5-氟-4-(4-甲基-2-(甲基氨基)噻唑-5-基)嘧啶-2-基)氨基)苯磺酰胺
- 化合物CDKI-73
- 1421693-22-2
- 3-((5-Fluoro-4-(4-methyl-2-(methylamino)thiazol-5-yl)pyrimidin-2-yl)amino)benzenesulfonamide
- toxicity,Inhibitor,low,AML,Acute,LS 007,myeloid,LS007,leukemia,CLL,Apoptosis,LS-007,endosome,Cyclin dependent kinase,CDKI73,CDKI-73,CDKI 73,inhibit,CDK
- asnuciclib
- CS-2259
- CDKI-73
(CDKI73)
- Benzenesulfonamide, 3-[[5-fluoro-4-[4-methyl-2-(methylamino)-5-thiazolyl]-2-pyrimidinyl]amino]-
- CDKI-73