JSH-150
目录号 : GC34204
JSH-150 is a highly selective and potent inhibitor of CDK9 with IC50 of 1 nM.
Cas No.:2247481-21-4
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Cell experiment: | The A375 (melanoma), A431 (squamous), BE(2)M17 (neuroblastoma), BE(2)M17 (neuroblastoma), CRL-2234 (hepatoma), COLO205 (colon cancer), A549 (lung adenocarcinoma), Ramos (B cell lymphoma), MV4-11 (AML), Ramos (B cell lymphoma), U937 (AML), CHL (hamster lung cell), and CHO (hamster ovary cell) cell lines are used. OCI-AML-3 (AML), SKM-1 (AML), MEC-1 (CLL), MEC-2 (CLL) and HL-60 (human promyelocytic leukemia cells) are used. Human GIST-T1 cells are used. MOLM-13 and MOLM14 cell lines are used. All the cells are grown in a humidified incubator at 37°C under 5% CO2. A375, A431, GIST-T1, A549, Colo205 and CHO cells are maintained in DMEM supplemented with 10% FBS, 1% Penicillin/Streptomycin. BE(2)M17 cells are cultured with 1:1 mixture of ATCC-formulated Eagle's minimum essential medium, and F12 Medium. MV4-11, MEC-1 and MEC-2 are grown in IMDM supplemented with 10% FBS, 1% Penicillin/Streptomycin. CRL-2234, U2932, U937, Ramos, MOLM13, MOLM14, OCI-AML-3, SKM-1, HL-60 and CHL are grown in RPMI 1640 medium supported with 10% FBS and 1% Penicillin/Streptomycin. Adherent cells are grown in tissue culture flasks until they are 85-95% confluent prior to use. For suspension cells, cells are collected by spin down at 800 rpm/min for 5 min before use. Cells are grown in 96-well culture plates (3000 cells/well). The compounds (e.g., JSH-150) at various concentrations are added into the plates. Cell proliferation is determined after treatment with compounds (e.g., JSH-150) for 72 h. Cell viability is measured using the Cell Titer-Glo assay and luminescence is measured in a multilabel reader[1]. |
Animal experiment: | Mice[1]Five-week-old female nu/nu mice are used. Prior to implantation, cells are harvested during exponential growth. Five million MV4-11 cells in PBS are formulated as a 1:1 mixture with Matrigel and injected into the subcutaneous space on the right flank of nu/nu mice. Daily oral administration is initiated when MV4-11 tumors have reached a size of 200-400 mm3. Animals are then randomized into treatment groups of 5 mice each for efficacy studies. JSH-150 is delivered daily in a HKI solution (0.5% methocellulose/0.4% Tween80 in ddH2O) by oral gavage. A range of doses of JSH-150 or its vehicle as control are administered. Female nu/nu mice bearing established MV4-11 tumor xenografts are treated with JSH-150 at 10, 20, and 30 mg/kg/d dosage or vehicle. Body weight is measured daily and tumor growth is measured every day after JSH-150 treatment. Tumor volume is calculated[1]. |
References: [1]. Beilei Wang, et al. Discovery of 4-(((4-(5-chloro-2-(((1s,4s)-4-((2-methoxyethyl)amino)cyclohexyl)amino)pyridin-4-yl)thiazol-2-yl)amino)methyl)tetrahydro-2H-pyran-4-carbonitrile (JSH-150) as a novel highly selective and potent CDK9 kinase inhibitor. Eur J Med Chem. 13 September 2018. | |
JSH-150 is a highly selective and potent inhibitor of CDK9 with IC50 of 1 nM.
JSH-150 exhibits an IC50 of 1 nM against CDK9 kinase in the biochemical assay and achieves around 300-10000-fold selectivity over other CDK kinase family members. In addition, it also displays high selectivity over other 468 kinases/mutants. JSH-150 displays potent antiproliferative effects against melanoma, neuroblastoma, hepatoma, colon cancer, lung cancer as well as leukemia cell lines. It can dose-dependently inhibit the phosphorylation of RNA Pol II, suppress the expression of MCL-1 and C-Myc, arrest the cell cycle and induce the apoptosis in the leukemia cells.[1]
In the MV4-11 cell-inoculated xenograft mouse model, 10 mg/kg dosage of JSH-150 can almost completely suppress the tumor progression. The high selectivity and good in vivo PK/PD profile suggests that JSH-150 will be a good pharmacological tool to study CDK9-mediated physiology and pathology as well as a potential drug candidate for leukemia and other cancers.[1]
[1] Beilei Wang, et al. Eur J Med Chem. 2018 Oct 5;158:896-916.
| Cas No. | 2247481-21-4 | SDF | |
| Canonical SMILES | COCCN[C@@H]1CC[C@@H](NC2=NC=C(Cl)C(C3=CSC(NCC4(C#N)CCOCC4)=N3)=C2)CC1 | ||
| 分子式 | C24H33ClN6O2S | 分子量 | 505.08 |
| 溶解度 | DMSO : 16.67 mg/mL (33.00 mM) | 储存条件 | Store at -20°C |
| General tips | 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 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.9799 mL | 9.8994 mL | 19.7988 mL |
| 5 mM | 0.396 mL | 1.9799 mL | 3.9598 mL |
| 10 mM | 0.198 mL | 0.9899 mL | 1.9799 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Discovery of 4-(((4-(5-chloro-2-(((1s,4s)-4-((2-methoxyethyl)amino)cyclohexyl)amino)pyridin-4-yl)thiazol-2-yl)amino)methyl)tetrahydro-2H-pyran-4-carbonitrile (JSH-150) as a novel highly selective and potent CDK9 kinase inhibitor
Eur J Med Chem 2018 Oct 5;158:896-916.PMID:30253346DOI:10.1016/j.ejmech.2018.09.025
Through a structure-guided rational drug design approach, we have discovered a highly selective inhibitor compound 40 (JSH-150), which exhibited an IC50 of 1 nM against CDK9 kinase in the biochemical assay and achieved around 300-10000-fold selectivity over other CDK kinase family members. In addition, it also displayed high selectivity over other 468 kinases/mutants (KINOMEscan S score(1) = 0.01). Compound 40 displayed potent antiproliferative effects against melanoma, neuroblastoma, hepatoma, colon cancer, lung cancer as well as leukemia cell lines. It could dose-dependently inhibit the phosphorylation of RNA Pol II, suppress the expression of MCL-1 and c-Myc, arrest the cell cycle and induce the apoptosis in the leukemia cells. In the MV4-11 cell-inoculated xenograft mouse model, 10 mg/kg dosage of 40 could almost completely suppress the tumor progression. The high selectivity and good in vivo PK/PD profile suggested that 40 would be a good pharmacological tool to study CDK9-mediated physiology and pathology as well as a potential drug candidate for leukemia and other cancers.