YKL-5-124 TFA是一种强效、选择性、不可逆的共价CDK7抑制剂，对CDK7和CDK7/Mat1/CycH复合物的IC50值分别为53.5nM和9.7nM。
Cas No.:2748220-93-9
Sample solution is provided at 25 µL, 10mM.
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YKL-5-124 TFA is a potent, selective, irreversible, and covalent CDK7 inhibitor with IC50 values of 53.5nM and 9.7nM for CDK7 and CDK7/Mat1/CycH, respectively[1]. YKL-5-124 TFA can reduce the phosphorylation level of RB protein in multiple myeloma cells, thereby decreasing the activity of E2F and regulating the cell cycle[2]. YKL-5-124 TFA has been widely used to inhibit tumor progression in both cell models and animal models[3].
In vitro, YKL-5-124 TFA treatment for 72 hours significantly inhibited the proliferation of NCCIT cells and TCam2 cells, with IC50 values of 121.1nM and 263.4nM, respectively[4]. Treatment with 250nM YKL-5-124 TFA for 24 hours significantly inhibited the cell cycle arrest of H929 cells and led to a deficiency in cellular glycolysis and a decrease in lactate production levels[5]. Treatment with 100nM YKL-5-124 TFA for 48 hours significantly inhibited the phosphorylation of the T-loop of CDK1 and CDK2 in the small cell lung cancer (SCLC) cell lines, impaired DNA replication, and led to DNA damage and the formation of micronuclei[6].
In vivo, YKL-5-124 TFA treatment via intraperitoneal injection (2.5mg/kg; three times a week, combined with JQ1 (25mg/kg; three times a week) for 25 days led to a significant suppression of tumor growth and extended survival in the IMR-32-xenograft mouse models[7].
References:
[1] Olson C M, Liang Y, Leggett A, et al. Development of a selective CDK7 covalent inhibitor reveals predominant cell-cycle phenotype[J]. Cell chemical biology, 2019, 26(6): 792-803. e10.
[2] Yao Y, Park W D, Morelli E, et al. Aberrant CDK7 Activity Drives the Cell Cycle and Transcriptional Dysregulation to Support Multiple Myeloma Growth: An Attractive Molecular Vulnerability[J]. Blood, 2021, 138: 2687.
[3] Yao Y, Park W D, Morelli E, et al. Targeting MM at the Nexus between Cell Cycle and Transcriptional Regulation Via CDK7 Inhibition[J]. Blood, 2020, 136: 1-2.
[4] Funke K, Düster R, Wilson P D G, et al. Transcriptional CDK inhibitors as potential treatment option for testicular germ cell tumors[J]. Cancers, 2022, 14(7): 1690.
[5] Yao Y, Ng J F, Park W D, et al. CDK7 controls E2F-and MYC-driven proliferative and metabolic vulnerabilities in multiple myeloma[J]. Blood, The Journal of the American Society of Hematology, 2023, 141(23): 2841-2852.
[6] Zhang H, Christensen C L, Dries R, et al. CDK7 inhibition potentiates genome instability triggering anti-tumor immunity in small cell lung cancer[J]. Cancer cell, 2020, 37(1): 37-54. e9.
[7] Gao Y, Volegova M, Nasholm N, et al. Synergistic anti-tumor effect of combining selective CDK7 and BRD4 inhibition in neuroblastoma[J]. Frontiers in Oncology, 2022, 11: 773186.
YKL-5-124 TFA是一种强效、选择性、不可逆的共价CDK7抑制剂，对CDK7和CDK7/Mat1/CycH复合物的IC50值分别为53.5nM和9.7nM[1]。YKL-5-124 TFA能够降低多发性骨髓瘤细胞中RB蛋白的磷酸化水平，从而减弱E2F活性并调控细胞周期[2]。YKL-5-124 TFA已被广泛用于在细胞模型和动物模型中抑制肿瘤进展[3]。
在体外，YKL-5-124 TFA处理72小时显著抑制了NCCIT细胞和TCam2细胞的增殖，IC50值分别为 121.1nM和263.4nM[4]。使用250nM的YKL-5-124 TFA处理H929细胞24小时，显著抑制了细胞周期阻滞，并导致细胞糖酵解缺陷和乳酸生成水平下降[5]。使用100nM的YKL-5-124 TFA处理小细胞肺癌（SCLC）细胞系48小时，显著抑制了CDK1和CDK2的T环磷酸化，损害DNA复制，并导致DNA损伤和微核形成[6]。
在体内，通过腹腔注射YKL-5-124 TFA（2.5mg/kg；每周三次）联合JQ1（25mg/kg；每周三次）治疗25天，显著抑制了IMR-32异种移植小鼠模型中的肿瘤生长，并延长了小鼠生存期[8]。
| Cell experiment [1]: | |
Cell lines | NCCIT cells |
Preparation Method | NCCIT cells were cultured in Dulbecco’s modified Eagle’s medium (DMEM) supplemented with 10% fetal bovine serum (FBS), 1% penicillin-streptomycin and 200mM L-glutamine at 37℃ in the presence of 7.5% CO2. 3000 cells were seeded per well of a 96-well cell culture plate in 100µl of cell culture medium for 24h, and were treated with different concentrations of YKL-5-124 TFA (1, 10, 100, 1000, and 10000nM). After 72 hours, cell viability was analyzed. |
Reaction Conditions | 1, 10, 100, 1000, and 10000nM; 72h |
Applications | YKL-5-124 TFA treatment significantly reduced the cell viability of NCCIT cells in a dose-dependent manner. |
| Animal experiment [2]: | |
Animal models | NOD.Cg-PrkdcscidIl2rgtm1Wjl/SzJ female mice |
Preparation Method | NOD.Cg-PrkdcscidIl2rgtm1Wjl/SzJ female mice (4-6 weeks old) were housed in temperature (23±2°C) and light-controlled (12:12-hour light-dark cycle) animal care facility. Subcutaneously inject 1×106 IMR-32 cells into mice. When a tumor volume of 200mm3 was reached, mice were treated with 2.5mg/kg YKL-5-124 TFA, 25mg/kg JQ1, or vehicle control (DMSO) by intraperitoneal (i.p.) injection, three times per week for 25 days. Tumor size and body weight were monitored three times per week, and tumor volume was calculated using the ellipsoid formula: 1/2(max diameter× minimal diameter2). |
Dosage form | 2.5mg/kg; three times a week for 25 days; i.p. |
Applications | YKL-5-124 TFA treatment combined with JQ1 led to a significant suppression of tumor growth and extended survival in mice. |
References: | |
| Cas No. | 2748220-93-9 | SDF | |
| Canonical SMILES | CC1(C)N(C(N[C@@H](C2=CC=CC=C2)CN(C)C)=O)CC3=C1NN=C3NC(C4=CC=C(NC(C=C)=O)C=C4)=O.FC(F)(C(O)=O)F | ||
| 分子式 | C30H34F3N7O5 | 分子量 | 629.63 |
| 溶解度 | DMSO: ≥ 100 mg/mL (158.82 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 | 1.5882 mL | 7.9412 mL | 15.8823 mL |
| 5 mM | 317.6 μL | 1.5882 mL | 3.1765 mL |
| 10 mM | 158.8 μL | 794.1 μL | 1.5882 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。
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