CDKI-73(Synonyms: LS-007)

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上海金畔生物科技有限公司为生命科学和医药研发人员提供生物活性分子抑制剂、激动剂、特异性抑制剂、化合物库、重组蛋白，专注于信号通路和疾病研究领域。

CDKI-73 (Synonyms: LS-007) 纯度: 99.58%

CDKI-73 (LS-007) 是具有口服活性的、高效的 CDK9 抑制剂，其对CDK9、CDK1 和 CDK2 的 Ki 值分别为 4 nM、4 nM 和 3 nM。CDKI-73 可下调 RNA 聚合酶 II 的磷酸化。CDKI-73 也是一种 Rab11 的抑制剂。

CDKI-73(Synonyms: LS-007)

CDKI-73 Chemical Structure

CAS No. : 1421693-22-2

规格 价格 是否有货 数量
10 mM * 1 mL in DMSO ￥3037 In-stock
2 mg ￥2333 In-stock
5 mg ￥3500 In-stock
10 mg ￥5000 In-stock
50 mg 询价
100 mg 询价

* Please select Quantity before adding items.

CDKI-73 相关产品

•相关化合物库:

  • Bioactive Compound Library Plus
  • Apoptosis Compound Library
  • Cell Cycle/DNA Damage Compound Library
  • Immunology/Inflammation Compound Library
  • Kinase Inhibitor Library
  • Anti-Cancer Compound Library
  • Anti-Aging Compound Library
  • Anti-Breast Cancer Compound Library
  • Anti-Pancreatic Cancer Compound Library
  • Anti-Blood Cancer Compound Library

生物活性

CDKI-73 (LS-007) is an orally active and highly efficacious CDK9 inhibitor, with Ki values of 4 nM, 4 nM and 3 nM for CDK9, CDK1 and CDK2, respectively. CDKI-73 down-regulates the RNAPII phosphorylation. CDKI-73 is also a novel pharmacological inhibitor of Rab11 cargo delivery and innate immune secretion[1][2][3][4].

IC50 & Target

CDK2

3.27 nM (IC50)

CDK9

5.78 nM (IC50)

CDK1

8.17 nM (IC50)

CDK4

8.18 nM (IC50)

CDK6

37.68 nM (IC50)

CDK7

134.26 nM (IC50)

CDK1

4 nM (Ki)

CDK2

3 nM (Ki)

CDK9

4 nM (Ki)

CDK7

91 nM (Ki)

体外研究
(In Vitro)

CDKI-73 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)[1].
CDKI-73 (0.1 μM, 4 h) inhibits the phosphorylation of serine 2 of RNA polymerase II and MCL1 protein expression in CLL cells[1].
CDKI-73 induced caspase-dependent apoptosis that was preceded by dephosphorylation of cdk9 and serine 2 of RNA polymerase II[1].
CDKI-73 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[3].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

Cell Viability Assay[1].

Cell Line: CLL cells.
Concentration: 0-1 μM.
Incubation Time: 48 h.
Result: Shows preferential cytotoxicity in CLL cells.

体内研究
(In Vivo)

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.[3].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model: MV4-11 tumor bearing mice[3].
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[3].
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. Its oral bioavailability (F) ranged from 54 to 85% across the three doses.

分子量

394.45

Formula

C15H15FN6O2S2
CAS 号

1421693-22-2
运输条件

Room temperature in continental US; may vary elsewhere.
储存方式

4°C, stored under nitrogen

*In solvent : -80°C, 6 months; -20°C, 1 month (stored under nitrogen)
溶解性数据
In Vitro: 

DMSO : ≥ 52 mg/mL (131.83 mM)

* “≥” means soluble, but saturation unknown.

配制储备液
浓度 溶剂体积 质量 1 mg 5 mg 10 mg
1 mM 2.5352 mL 12.6759 mL 25.3518 mL
5 mM 0.5070 mL 2.5352 mL 5.0704 mL
10 mM 0.2535 mL 1.2676 mL 2.5352 mL

*

请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。
储备液的保存方式和期限：-80°C, 6 months; -20°C, 1 month (stored under nitrogen)。-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。

In Vivo:

请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照 In Vitro 方式配制澄清的储备液，再依次添加助溶剂：

——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用； 以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶

  • 1.

    请依序添加每种溶剂： 10% DMSO    40% PEG300    5% Tween-80    45% saline

    Solubility: ≥ 2.67 mg/mL (6.77 mM); Clear solution

    此方案可获得 ≥ 2.67 mg/mL (6.77 mM，饱和度未知) 的澄清溶液。

    以 1 mL 工作液为例，取 100 μL 26.7 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；向上述体系中加入50 μL Tween-80，混合均匀；然后继续加入 450 μL生理盐水定容至 1 mL。

    将 0.9 g 氯化钠，完全溶解于 100 mL ddH₂O 中，得到澄清透明的生理盐水溶液

*以上所有助溶剂都可在 上海金畔生物科技有限公司 网站选购。
参考文献

  • [1]. Lam F, et al. Targeting RNA transcription and translation in ovarian cancer cells with pharmacological inhibitor CDKI-73. Oncotarget. 2014 Sep 15;5(17):7691-704.

    [2]. Elisabeth Walsby, et al. A novel Cdk9 inhibitor preferentially targets tumor cells and synergizes with fludarabine. Oncotarget. 2014 Jan; 5(2): 375–385.

    [3]. Muhammed H Rahaman, et al. CDKI-73: an orally bioavailable and highly efficacious CDK9 inhibitor against acute myeloid leukemia. Invest New Drugs. 2019 Aug;37(4):625-635.

    [4]. Alexandra Sorvina, et al. CDKI-73 is a Novel Pharmacological Inhibitor of Rab11 Cargo Delivery and Innate Immune Secretion. Cells. 2020 Feb 5;9(2):372.

    [5]. Shao Xie, et al. Antitumor action of CDK inhibitor LS-007 as a single agent and in combination with ABT-199 against human acute leukemia cells. Acta Pharmacol Sin. 2016 Nov; 37(11): 1481–1489.

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