PNU112455A hydrochloride
目录号 : GC39421
PNU112455A hydrochloride是CDK2和CDK5的ATP位点的竞争性抑制剂，其对CDK2和CDK5中ATP位点的Km值分别为3.6μM和3.2μM。
Cas No.:21886-12-4
Sample solution is provided at 25 µL, 10mM.
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PNU112455A hydrochloride is a competitive inhibitor of the ATP sites of CDK2 and CDK5, with the Km values for the ATP sites of CDK2 and CDK5 being 3.6 and 3.2μM, respectively [1]. CDK5 is a multifunctional kinase physiologically involved in proliferation, invasion, angiogenesis, genome instability and metabolism in the development of cancers [2].
In vivo, PNU112455A (150mg/kg/day; i.p.) was administered to mice subcutaneously injected with Hepa 1-6 cells for 4 days. This treatment effectively upregulated the level of PD-L1 in tumor cells, promoted the response to anti-PD-1 immunotherapy, and prolonged the survival time of mice with liver cancer tumors[2].
References:
[1] Clare PM, et al. The cyclin-dependent kinases cdk2 and cdk5 act by a random, anticooperative kinetic mechanism. J Biol Chem. 2001 Dec 21;276(51):48292-9.
[2] Zhang R, Wang J, Du Y, et al. CDK5 destabilizes PD-L1 via chaperon-mediated autophagy to control cancer immune surveillance in hepatocellular carcinoma[J]. Journal for Immunotherapy of Cancer, 2023, 11(11): e007529.
PNU112455A hydrochloride是CDK2和CDK5的ATP位点的竞争性抑制剂，其对CDK2和CDK5中ATP位点的Km值分别为3.6μM和3.2μM[1]。CDK5是一种多功能激酶，在癌症的发展过程中参与细胞增殖、侵袭、血管生成、基因组不稳定性和代谢等生理过程[2]。
在体内，PNU112455A（150mg/kg/day, i.p.）治疗皮下注射Hepa 1-6细胞的小鼠4天，有效上调肿瘤细胞中PD-L1的水平，促进抗PD-1免疫疗法的反应，并延长荷瘤肝癌小鼠的存活时间 [2]。
| Animal experiment [1]: | |
Animal models | C57BL/6 mice |
Preparation Method | C57BL/6 mice (6–8 weeks old) were purchased from Qizhen Laboratory Animals. Hepa1-6 (1×106 cells) were implanted subcutaneously into the right flank of mice. The PD-1 antibody (10mg/kg) and PNU112455A (150mg/kg; solvent: PBS/DMSO/Solutol 8:1:1) were injected intraperitoneally on days 9, 12, 15, and 18. Tumors were measured every 3 days with a caliper, and tumor volume was calculated using the formula: π/6×length×width2. Mice were sacrificed when tumors reached 1500mm3. |
Dosage form | 150mg/kg/d; 4 days |
Applications | PNU112455A effectively upregulates the tumorous PD-L1 level, promotes the response to anti-PD-1 immunotherapy,and prolongs the survival time of mice bearing HCC tumors. |
References: | |
| Cas No. | 21886-12-4 | SDF | |
| Canonical SMILES | O=S(C1=CC=C(NC2=NC=NC(N)=C2)C=C1)(N)=O.[H]Cl | ||
| 分子式 | C10H12ClN5O2S | 分子量 | 301.75 |
| 溶解度 | DMSO: 125 mg/mL (414.25 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 | 3.314 mL | 16.57 mL | 33.14 mL |
| 5 mM | 0.6628 mL | 3.314 mL | 6.628 mL |
| 10 mM | 0.3314 mL | 1.657 mL | 3.314 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。
Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet