CCT196969 - Raf 抑制剂 - 生命科学试剂 - MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemECCT196969Cat. No.: HY-12846CAS No.: 1163719-56-9分式: CHFNO分量: 513.52作靶点: Raf作通路: MAPK/ERK Pathway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 : 32 mg/mL (62.31 mM)* means soluble, but satur

2、ation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制备储备液1 mM 1.9473 mL 9.7367 mL 19.4734 mL5 mM 0.3895 mL 1.9473 mL 3.8947 mL10 mM 0.1947 mL 0.9737 mL 1.9473 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，配制前请先配制澄清的储备液，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；澄清的储备液可以根据储存

3、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: 2.08 mg/mL (4.05 mM); Clear solution2. 请依序添加每种溶剂： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.08 mg/mL (4.05 mM); Clear solution3. 请依序添加每种溶剂： 10% DMSO 90% corn oil1/3 Master of Small Molecules

4、 您边的抑制剂师www.MedChemESolubility: 2.08 mg/mL (4.05 mM); Clear solutionBIOLOGICAL ACTIVITY物活性 CCT196969种泛-Raf 抑制剂，抑制 B-Raf，BRafV600E 和 CRAF，IC50 分别为 0.1, 0.04, 和 0.01 M。IC50 & Target BRafV600E Braf CRAF LCK0.04 M (IC50) 0.1 M (IC50) 0.01 M (IC50) 0.02 M (IC50)SRC0.03 M (IC50)体外研究 CCT196969 is a pan-Raf

5、 inhibitor with anti-SRC activity. CCT196969 is an orally available, well-tolerated B-Raf inhibitor that directly inhibits B-RafV600E in cells. CCT196969 inhibits B-Raf at 100 nM and B-RafV600Eat 40 nM. It inhibits CRaf at 12 nM, SRC at 26 nM, and LCK at 14 nM. CCT196969 is active againstmelanoma an

6、d colorectal cancer cell lines that are mutant for B-Raf. CCT196969 induces caspase 3 andPARP cleavage, demonstrating that it induces apoptosis 1.体内研究 CCT196969 is extremely well tolerated and does not produce any significant adverse effects in vivo. Itinhibits the growth of NRAS mutant DO4 tumor xe

7、nografts in nude mice. CCT196969 inhibits ERK and SRCand induce tumor regression in a PDX from the resistant tumor without causing body weight loss in the mice1.PROTOCOLCell Assay 1 Cultured cells are seeded into 96-well plates (2,000 cells per well). At 24 hr later, serial dilutions of the B-Rafinh

8、ibitors PLX4720 and SB590885, the MEK inhibitor PD184352, or compounds CCT241161 andCCT196969 are added. Cells are incubated for a further 72 hr, and viability is measured by CellTiter-Gloassays. Relative survival in the presence of drugs is normalized to the untreated controls after backgroundsubtr

9、action 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Mice: Tumors are established in female nude mice. Treatment is by oral gavage daily with vehicle (5%Administration 1 DMSO, 95% water), 90 mg/kg PLX4720, 20 mg/kg CCT196969, or 20 mg/kg CCT2

10、41161. All the inhibitorsare administered 7 days/week, with no weekend break. Tumor size is determined by caliper measurementsof tumor length, width, and depth; volume is calculated as volume = 0.5236lengthwidthdepth (inmillimeters) 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.REFERENCES1. Girotti MR, et al. Paradox-breaking RAF inhibitors that also target SRC are effective in drug-resistant BRAF mutant melanoma. Cancer2/3 Master of Small Molecules 您边的抑制剂师www.MedChemECell. 2015 Jan 12;27(1):85-96.McePdfHeightCaution: Product has not be