Powder: -20°C for 3 years | In solvent: -80°C for 1 year
R547 (Ro 4584820) 是一种口服有效,选择性, ATP 竞争性CDK 抑制剂,对 CDK1/cyclin B、 CDK2/cyclin E 和 CDK4/cyclin D1 作用的Ki 值分别为 2 nM、3 nM、1 nM。
规格 | 价格/CNY | 货期 | 数量 | |
---|---|---|---|---|
1 mg | ¥ 632 | 现货 | ||
2 mg | ¥ 915 | 现货 | ||
5 mg | ¥ 1,480 | 现货 | ||
10 mg | ¥ 2,310 | 现货 | ||
25 mg | ¥ 3,920 | 现货 | ||
50 mg | ¥ 5,590 | 现货 | ||
100 mg | ¥ 7,830 | 现货 | ||
500 mg | ¥ 15,700 | 现货 | ||
1 mL * 10 mM (in DMSO) | ¥ 1,730 | 现货 |
产品描述 | R547 (Ro 4584820) is a potent ATP-competitive inhibitor of CDK1/2/4 with Ki of 2 nM/3 nM/1 nM. It is less potent to CDK7 and GSK3α/β, while inactive to other kinases. Phase 1. |
靶点活性 | CDK4-CyclinD1:1 nM(Ki), CDK2-CyclinE:3 nM(Ki), CDK1-CyclinB:2 nM(Ki) |
体外活性 | R547 identified as a diaminopyrimidine compound, which is a potent and selective ATP-competitive CDK inhibitor. R547 effectively inhibits CDK1/cyclinB, CDK2/cyclinE, and CDK4/cyclinD1(Ki=1-3 nM) and is inactive(Ki>5,000 nM) against a panel of >120 unrelated kinases. R547 effectively inhibits the proliferation of tumor cell lines independent of multidrug resistant status, histologic type, retinoblastoma protein, or p53 status, with IC50s <0.60 μM. R547 reduces phosphorylation of the cellular retinoblastoma protein at specific CDK phosphorylation sites at the same concentrations that induced cell cycle arrest, suggesting a potential pharmaco dynamics marker for clinical use. R547 inhibits the proliferation of tumor cell lines and is active in all 19 cell lines tested irrespective of tissue of origin, multidrug resistance (MDR), p53, or retinoblastoma status. [1] R547 possessing both 5-and 6-fluoro substitution culminated in an Inhibitor with low, single-digit nanomolar potency against the CDKs(Ki=0.001,0.003,and 0.001 μM for CDK1,CDK2, and CDK4,respectively) and excellent cellular potency (IC50=0.08 μM,HCT116 cell line). [2] |
体内活性 | R547 administered with oral and i.v. dosing in multiple established human tumor significantly inhibits tumor activity(P < 0.01). R547 administered orally at dose of 40 mg/kg daily in colon, lung, breast, prostate, and melanoma human tumor xenograft models shows significant TGI (79-99%). R547 is equally efficacious (TGI, 61-95%) when dosed with 40 mg/kg i.v. once weekly. These doses of R547 are not toxic and did not result in body weight loss. R547 does not show signs of overt toxicity during the course of the 3-week study and any gross pathology at necropsies done at the end of the studies. [1] R547 inhibits tumor growth up to 95% in the HCT116 human colorectal tumor xenograft model in nude mice . R547 causes significant TGI in all of the models tested when dosed orally and i.v. at or below the maximum tolerated dose. R547 inhibits phosphorylation of retinoblastoma protein in tumors at the efficacious exposures in tumor xenograft models, providing a pharmacodynamic biomarker for clinical use. R547 reported here suggests that this is a promising molecule for evaluation in the treatment of solid tumors. [2] |
别名 | Ro 4584820 |
分子量 | 441.45 |
分子式 | C18H21F2N5O4S |
CAS No. | 741713-40-6 |
Powder: -20°C for 3 years | In solvent: -80°C for 1 year
Ethanol: < 1 mg/mL (insoluble or slightly soluble)
H2O: < 1 mg/mL (insoluble or slightly soluble)
DMSO: 56 mg/mL (126.9 mM)
可选溶剂 | 浓度 体积 质量 | 1 mg | 5 mg | 10 mg | 25 mg |
DMSO | 1 mM | 2.2653 mL | 11.3263 mL | 22.6526 mL | 56.6316 mL |
5 mM | 0.4531 mL | 2.2653 mL | 4.5305 mL | 11.3263 mL | |
10 mM | 0.2265 mL | 1.1326 mL | 2.2653 mL | 5.6632 mL | |
20 mM | 0.1133 mL | 0.5663 mL | 1.1326 mL | 2.8316 mL | |
50 mM | 0.0453 mL | 0.2265 mL | 0.4531 mL | 1.1326 mL | |
100 mM | 0.0227 mL | 0.1133 mL | 0.2265 mL | 0.5663 mL |
对于不同动物的给药剂量换算,您也可以参考 更多...
请在以下方框中输入您的动物实验信息后点击计算,可以得到母液配置方法和体内配方的制备方法: 比如您的给药剂量是10 mg/kg,每只动物体重20 g,给药体积100 μL,一共给药动物10 只,您使用的配方为5% DMSO+30% PEG300+5% Tween 80+60% ddH2O。那么您的工作液浓度为2 mg/mL。
母液配置方法:2 mg 药物溶于 50 μL DMSO (母液浓度为 40 mg/mL), 如您需要配置的浓度超过该产品的溶解度,请先与我们联系。
体内配方的制备方法:取 50 μL DMSO 主液,加入 300 μL PEG300, 混匀澄清,再加 50 μL Tween 80,混匀澄清,再加 600 μL ddH2O, 混匀澄清。
您可能有的问题的答案可以在抑制剂处理说明中找到,包括如何准备库存溶液,如何存储产品,以及基于细胞的分析和动物实验需要特别注意的问题。
R547 741713-40-6 Apoptosis Cell Cycle/Checkpoint PI3K/Akt/mTOR signaling Stem Cells Tyrosine Kinase/Adaptors GSK-3 PKA CDK Glycogen synthase kinase 3 kinase multiple tumor cyclin-dependent R 547 Cyclin dependent kinase human Inhibitor Ro 4584820 Glycogen synthase kinase-3 R-547 inhibit inhibitor