CCT-245737CAS号: 1489389-18-5分子式: C16H16F3N7O分子量: 379.34描述纯度储存/保存方法别名可溶性/溶解性靶点In vitro(体外研究)In vivo(体内研究)
产品描述 | |
描述 |
CCT-245737 是一种有效的,选择性的 Chk1 抑制剂,IC50 值为 1.3 nM,选择性是 Chk2 (IC50,2440 nM) 的 1000 多倍。 |
纯度 |
>98%
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储存/保存方法 |
Store at -20℃ for one year(Powder);Store at 2-4℃ for two weeks;Store at -20℃ for six months after dissolution.
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基本信息 | |
别名 |
CCT245737
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可溶性/溶解性 |
DMSO: ≥ 32 mg/mL
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生物活性 | |
靶点 |
Chk1
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In vitro(体外研究) |
CCT245737 is a potent inhibitor of recombinant human CHK1 with IC50 of 1.4±0.3 nM (mean±SD, n = 3, EZ Reader II assay). There is > 1,000-fold selectivity for CHK1 versus the functionally important kinases CDK1 and CHK2 (IC50=1.26-2.44 and 9.03 μM, respectively), and at least a 90-fold selectivity against cross-reacting kinases such as ERK8, PKD1, RSK1 and 2. CCT245737 potently inhibits cellular CHK1 activity (IC50 30-220nM) and enhances gemcitabine and SN38 cytotoxicity in multiple human tumor cell lines and human tumor xenograft models. It can abrogate an etoposide-induced G2/M arrest. CCT245737 has high cell permeability, as measured by transport across a CaCo2 cell monolayer.
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In vivo(体内研究) |
Mouse oral bioavailability is complete (100%) with extensive tumor exposure. CCT245737 shows significant single-agent activity against a MYC-driven mouse model of B-cell lymphoma. An i.v. dose of 10mg/kg CCT245737 into BALB/c mice gives a peak plasma concentration of 4μmol/L, with a half-life of 2.86h, an AUC0-∞ of 9.96μmol.h/L, a plasma clearance of 2.1L/h/kg and a large volume of distribution (0.19L). The equivalent oral dose gave an almost identical profile with an AUC0-∞ of 10.4μmol.h/L showing complete oral bioavailability (F = 105%). In a word, CCT245737 shows complete oral bioavailability with linear pharmacokinetics and high tumor/plasma ratios consistent with extensive tumor exposure. Adequate CCT245737 tumor drug exposure takes a significant antitumor activity.
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分子结构图