2. Cell Cycle/DNA Damage Protein Tyrosine Kinase/RTK Apoptosis Epigenetics
  3. CDK DYRK Apoptosis Bcl-2 Family c-Myc Caspase PARP DNA/RNA Synthesis
  4. Tambiciclib dimaleate

Tambiciclib dimaleate  (Synonyms: GFH009 dimaleate; JSH-009 dimaleate; SLS009 dimaleate)

目录号: HY-X0009A
产品使用指南 技术支持

Tambiciclib dimaleate (GFH009, JSH-009) 是一种口服活性、高效且高选择性的 CDK9 抑制剂 (IC50 = 1 nM)，对其他 CDK 亚型的选择性超过 200 倍，对 DYRK1A/B 的选择性超过 100 倍，并在 468 种激酶/突变体筛选中表现出卓越的选择性。在急性髓系白血病 (AML) 小鼠模型中，Tambiciclib dimaleate 通过抑制 RNA Pol II 磷酸化、下调 MCL1 与 MYC 表达并诱导细胞凋亡 (apoptosis)，展现出显著的体外和体内抗白血病活性。Tambiciclib dimaleate 可用于急性髓系白血病的相关研究。

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Tambiciclib dimaleate

Tambiciclib dimaleate Chemical Structure

CAS No. : 2559759-04-3

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规格 价格 是否有货
5 mg ￥1100
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10 mg ￥1900
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25 mg ￥4200
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Tambiciclib dimaleate 的其他形式现货产品:

Customer Review

Other Forms of Tambiciclib dimaleate:

Tambiciclib dimaleate 相关抗体

Top Publications Citing Use of Products

MCE 顾客使用本产品发表的 1 篇科研文献

查看 CDK 亚型特异性产品:

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CDK1 CDK2 CDK3 CDK4 CDK5 CDK6 CDK7 CDK8 CDK9 CDK11 CDK12 CDK13 CDK14 CDK16 CDK19 CDC CLK Pho85 CDK10 CDK15 CDK17 CDK18 CDK20 PITSLRE

查看 DYRK 亚型特异性产品:

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DYRK1 DYRK2 DYRK3 DYRK4 HIPK PRP4

查看 Bcl-2 Family 亚型特异性产品:

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Bcl-2 Bcl-xL Bcl-W Mcl-1 Bfl-1 Bcl-B Bax Bak Bim BNIP3

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Caspase 1 Caspase 2 Caspase 3 Caspase 4 Caspase 5 Caspase 6 Caspase 7 Caspase 8 Caspase 9 Caspase 10 Caspase 12 Caspase Caspase 11 Caspase-13

查看 PARP 亚型特异性产品:

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PARP PARP1 PARP2 PARP3 PARP4 TNKS1/PARP5A TNKS2/PARP5B PARP7 PARP10 PARP14 PARP15 PARP12 PARP16

  • 生物活性

  • 纯度 & 产品资料

  • 参考文献

生物活性

Tambiciclib (GFH009, JSH-009) dimaleate is an orally active, highly potent and selective CDK9 inhibitor (IC50 = 1 nM), demonstrating >200-fold selectivity over other CDKs, >100-fold selectivity over DYRK1A/B, and excellent selectivity over 468 kinases/mutants. Tambiciclib dimaleate demonstrates potent in vitro and in vivo antileukemic efficacy in acute myeloid leukemia (AML) mouse models by inhibiting RNA Pol II phosphorylation, downregulating MCL1 and MYC, and inducing apoptosis. Tambiciclib dimaleate can be used for AML research[1].

IC50 & Target[1]

CDK9/cyclinT1

1 nM (IC50)

CDK1/cyclinB

5410 nM (IC50)

CDK2/cyclinA

6850 nM (IC50)

CDK3/cyclin E1

>10,000 nM (IC50)

Cdk5/p25

6950 nM (IC50)

CDK7/Cyclin H/MNAT1

3700 nM (IC50)

CDK8/cyclin C

>10,000 nM (IC50)

CDK11

>10,000 nM (IC50)

CDK14/Cyclin Y

2710 nM (IC50)

CDK16/Cyclin Y

195 nM (IC50)

体外研究
(In Vitro)

Tambiciclib (JSH009) dimaleate (72 小时) 可有效抑制多种 AML 细胞系和患者来源的原代细胞 (GI50 < 50 nM) 的生长，但对正常外周血单核细胞的抑制作用显著较弱 (GI50 > 10 μM)，证明了其良好的安全性[1]。
Tambiciclib dimaleate (0.03-3 μM，2 小时) 在 OCI-AML-3、MV4-11 和 HL-60 细胞中可有效且剂量依赖性地抑制 RNA Pol II 在 Ser2 位点的磷酸化 (EC50 < 300 nM)，同时对 CDK7 介导的 RNA Pol II 在 Ser5 位点或 CDK9 在 Thr186 位点的磷酸化无影响，证实了其对 CDK7 具有高度选择性[1]。
Tambiciclib dimaleate (0.03-0.1 μM，10 小时) 可下调 MV4-11 细胞中 MCL1 和 MYC 的转录水平表达，并伴随整体转录水平的广泛降低[1]。
Tambiciclib dimaleate (0.01-0.1 μM，24 小时) 通过引发 caspase-3 和 PARP 的裂解，诱导 OCI-AML-3、MV4-11 和 HL-60 细胞系发生凋亡[1]。
Tambiciclib dimaleate (0.01-0.05 μM，24 小时) 对 MV4-11 和 OCI-AML-3 细胞的细胞周期分布没有影响，这与 MV4-11 细胞中关键细胞周期调节因子 (E2F1、Cyclin D1、CDC2) 的表达未发生显著变化的结果一致[1]。

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Tambiciclib dimaleate 相关抗体:

Western Blot Analysis[1]

Cell Line: OCI-AML3, MV4-11, and HL-60 cells
Concentration: 0.01, 0.03, and 0.1 μM
Incubation Time: 24 h
Result: Increased cleaved-caspase3 and cleaved-PARP levels in all three cell lines.
Elicited a markedly weaker PARP cleavage signal in OCI-AML3 cells compared to MV4-11 and HL-60 cells.

Western Blot Analysis[1]

Cell Line: OCI-AML-3, MV4-11, and HL-60 cells
Concentration: 0.03, 0.1, 0.3, 1, and 3 μM
Incubation Time: 2 h
Result: Reduced p-RNA Pol II Ser2 and levels in a dose-dependent manner.
Did not affect the phosphorylation levels of RNA Pol II Ser5 or CDK9 Thr186, which are controlled by CDK7, even at a concentration of 3 μM.
Reduced MCL-1 and C-MYC protein levels.

Real Time qPCR[1]

Cell Line: MV4-11 cells
Concentration: 0.03 and 0.1 μM
Incubation Time: 10 h
Result: Decreased MYC and MCL1 mRNA levels in MV4-11 cells.
药代动力学
(Parmacokinetics)[1]
Species Dose Route Indicator value
Rat 1 mg/kg i.v. T1/2 4.303 h
Rat 20 mg/kg p.o. T1/2 2.313 h
Rat 1 mg/kg i.v. Tmax 0.033 h
Rat 20 mg/kg p.o. Tmax 4.000 h
Rat 1 mg/kg i.v. Cmax 167.7 ng/mL
Rat 20 mg/kg p.o. Cmax 119.7 ng/mL
Rat 1 mg/kg i.v. AUC0-t 76.3 ng·h/mL
Rat 20 mg/kg p.o. AUC0-t 681 ng·h/mL
Rat 1 mg/kg i.v. AUC0-∞ 81.9 ng·h/mL
Rat 20 mg/kg p.o. AUC0-∞ 770 ng·h/mL
Rat 1 mg/kg i.v. Vz 73437 mL/kg
Rat 20 mg/kg p.o. Vz 89877 mL/kg
Rat 1 mg/kg i.v. CL 12335 mL/h/kg
Rat 20 mg/kg p.o. CL 27431 mL/h/kg
Rat 1 mg/kg i.v. MRT0-∞ 3.227 h
Rat 20 mg/kg p.o. MRT0-∞ 7.45 h
Rat 20 mg/kg p.o. F 47 %
体内研究
(In Vivo)

Tambiciclib dimaleate (10 与 20 mg/kg，口服给药，每日一次，持续 3 周) 在 MV4-11 细胞异种移植小鼠模型中可有效抑制肿瘤生长，且未表现出明显毒性[1]。
Tambiciclib dimaleate (10 与 15 mg/kg，口服给药，每日一次，持续至实验终点) 在 MV4-11 细胞移植小鼠模型中可剂量依赖性地延长总生存期[1]。
Tambiciclib dimaleate (10 与 20 mg/kg，口服给药，每日一次，持续约 2 周) 在急性髓系白血病 (AML) PDX 小鼠模型中显示出剂量依赖性的抗肿瘤进展效果[1]。

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model: Balb/c nu mice subcutaneously injected with MV4-11 cells[1]
Dosage: 10 and 20 mg/kg
Administration: p.o., daily for 3 weeks
Result: Inhibited tumor growth with TGI of 25.2 % at 10 mg/kg.
Almost completely suppressed tumor progression (TGI = 98.7 %) at a 20 mg/kg dosage.
Revealed no apparent behavioral changes or body weight loss in mice.
Suppressed proliferation (Ki67) and induced apoptosis in a dose dependent manner.
Animal Model: Female NOD-SCID mice (5 weeks old) intravenously injected with MV4-11 cells[1]
Dosage: 10 and 15 mg/kg
Administration: p.o., daily until endpoint
Result: Prolonged overall survival in a dose-dependent manner.
Achieved almost 200 days of survival in mice at 15 mg/kg.
Animal Model: Female NCG mice (5 weeks old) subcutaneously implanted with AML patient tumors[1]
Dosage: 10 and 20 mg/kg
Administration: p.o., daily for approximately 2 weeks
Result: Resulted in a TGI of 53.4 % without any apparent overall toxicity at 20 mg/kg.
Displayed dose-dependent efficacy against antitumor progression.
Downregulated the phosphorylation of RNA Pol II and Mcl1/MYC protein levels.
Clinical Trial
分子量

751.25

Formula

C33H43ClN6O10S
CAS 号
性状

固体

颜色

Off-white to light yellow

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)

纯度 & 产品资料
参考文献

Tambiciclib dimaleate 相关分类

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  • Do most proteins show cross-species activity?

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Keywords:

Tambiciclib dimaleate2559759-04-3GFH009 dimaleateJSH-009 dimaleateSLS009 dimaleateCDKDYRKApoptosisBcl-2 Familyc-MycCaspasePARPDNA/RNA SynthesisCyclin dependent kinaseDual specificity tyrosine phosphorylation regulated kinaseDual specificity tyrosine regulated kinaseMycpoly ADP ribose polymeraseCDK9DYRK1A/BantileukemicAMLRNA Pol IIMCL1MYCapoptosisOCI-AML-3MV4-11HL-60Inhibitorinhibitorinhibit

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