CYC065-DataSheet-生命科学试剂-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemECYC065Cat. No.: HY-101212CAS No.: 1070790-89-4分式: CHNO分量: 397.52作靶点: CDK作通路: Cell Cycle/DNA Damage储存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性数据体外实验 DMSO : 100 mg/mL (251.56 mM)* means soluble, but s

2、aturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制备储备液1 mM 2.5156 mL 12.5780 mL 25.1560 mL5 mM 0.5031 mL 2.5156 mL 5.0312 mL10 mM 0.2516 mL 1.2578 mL 2.5156 mL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，并请注意储备液的保存式和期限。体内实验请根据您的实验动物和给药式选择适当的溶解案，配制前请先配制澄的储备液，再依次添加助溶剂(为保证实验结果的可靠性，体内实验的作液，建议您现现配，当天使；澄的储备液可以根

3、据储存条件，适当保存；以下溶剂前的百分 指该溶剂在您配制终溶液中的体积占)：1. 请依序添加每种溶剂： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (6.29 mM); Clear solution2. 请依序添加每种溶剂： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.5 mg/mL (6.29 mM); Clear solution3. 请依序添加每种溶剂： 10% DMSO 90% corn oil1/3 Master of Small Molecule

4、s 您边的抑制剂师www.MedChemESolubility: 2.5 mg/mL (6.29 mM); Clear solutionBIOLOGICAL ACTIVITY物活性 CYC065第代服有效的 ATP 竞争性的 CDK2 / CDK9 激酶抑制剂。IC50 & Target CDK2 CDK9体外研究 CYC065 blocks cells in the G1 phase of the cell cycle and inhibits cell growth specifically in cyclin E1(CCNE1)-overexpressing uterine serous

5、 carcinomas (USCs). USC cell lines expressing high CCNE1 mRNAand protein levels to be significantly more sensitive to treatment with CYC065 in vitro when compared withlow CCNE1-expressing cell lines (IC50: means.d.=124.157.8nM in CCNE1-overexpressing USC cell linesvs 415117.5nM in CCNE1 low expresso

6、rs, respectively; P=0.0003). Importantly, low concentrations ofCYC065 (i.e., 100nM) causes an arrest in the G1 phase of the cell cycle only in the CCNE1-overexpressingUSC cell lines (i.e., USC-ARK-2, USC-ARK-7) 1.体内研究 To evaluate the therapeutic potential of CYC065 as a single agent, USC-ARK-2-deriv

7、ed xenografts aretreated daily with CYC065 (22.5mg/kg) for a 3-week period. Tumor size and mouse weight are recorded twotimes a week. The daily administration of CYC065 results in a significant reduction of tumor growth comparedwith the vehicle-treated mice (P=0.012 starting at day 9 of the treatmen

8、t). No significant weight loss isreported during the entire treatment period 1.PROTOCOLCell Assay 1 The effect of CYC065 on the viability and IC50 of USC-ARK-1, USC-ARK-2, USC-ARK-7, USC-ARK-4 andUSC-ARK-6 USC primary cell lines is determined in flow-cytometry assay. Briefly, tumour cells are plated

9、 insix-well plates and treated with a titration of CYC065 concentrations (i.e., ranging from 100 to 500nM). After72h, cells are harvested, washed and stained with propidium iodide (PI; 5g/mL) for flow cytometric counts.The percentage of viable cells is then normalised considering the vehicle-treated

10、 cells as 100% viable. Half-maximal inhibitory concentration values are determined using GraphPad Prism5 version 6. For drugcombination studies, USC-ARK-1 and USC-ARK-2 cell lines are incubated with the combination of Taselisiband CYC065 at multiple paired concentrations including the IC50, the IC50

11、/2 and the IC50*2 of each cell lineto the corresponding drug (i.e., 10nM of Taselisib and 198nM of CYC065 for USC-ARK-1 and 50nM ofTaselisib and 62.5nM of CYC065 for USC-ARK-2). Synergism is assessed by the combination index (CI). CIvalues 1.MCE has not independently confirmed the accuracy of these

12、methods. They are for reference only.Animal Mice 1Administration 1 The in vivo efficacy of CYC065 used as a single agent is evaluated on xenograft mouse models derived fromthe CCNE1-amplified USC-ARK-2 USC cell line. Xenografts derived from the CCNE1-amplified, PIK3CA-mutated USC-ARK-1 cell line are

13、 used for evaluating the in vivo combination of CYC065 and Taselisib.Briefly, 5-7-week-old SCID mice are injected into the subcutaneous region with USC cells. A minimum of five2/3 Master of Small Molecules 您边的抑制剂师www.MedChemEanimals per group are used. Treatments are administrated by oral gavage sta

14、rting 1 week after tumorimplantation when the size of the tumor is 0.125-0.150cm3. Uterine serous carcinoma-ARK-2-derivedxenografts are divided into two groups: one group of animal receive the vehicle, whereas the experimentalgroup receive CYC065 (22.5mg/kg daily for 3 weeks). Uterine serous carcino

15、ma-ARK-1-derived xenograftsare instead divided into four groups: one group receive the vehicle (0.5% methylcellulose-0.2% Tween-80),one group receive CYC065 (22.5mg/kg daily for 3 weeks), one group receive Taselisib (10 mg/kg daily, 5days per week per 3 weeks) and the last group receive the combinat

16、ion of CYC065 and Taselisib. The sizeof the tumor at the initiation of treatment is 0.125-0.150cm3. Mouse weight and tumor size is recorded twotimes a week for the entire experimental period. Tumor volume is calculated.MCE has not independently confirmed the accuracy of these methods. They are for reference only.REFERENCES1. Cocco E, et al. Dual CCNE1/PIK3CA targeting is synergistic in CCNE1-amplified/PIK3CA-mutated uterine serous carcinomas in vitroand