CCT196969 - Raf 抑制劑 - 生命科學(xué)試劑 - MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemECCT196969Cat. No.: HY-12846CAS No.: 1163719-56-9分式: CHFNO分量: 513.52作靶點(diǎn): Raf作通路: MAPK/ERK Pathway儲存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性數(shù)據(jù)體外實(shí)驗(yàn) DMSO : 32 mg/mL (62.31 mM)* means soluble, but satur

2、ation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制備儲備液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請根據(jù)產(chǎn)品在不同溶劑中的溶解度，選擇合適的溶劑配制儲備液，并請注意儲備液的保存式和期限。體內(nèi)實(shí)驗(yàn)請根據(jù)您的實(shí)驗(yàn)動(dòng)物和給藥式選擇適當(dāng)?shù)娜芙獍福渲魄罢埾扰渲瞥吻宓膬湟?，再依次添加助溶?為保證實(shí)驗(yàn)結(jié)果的可靠性，體內(nèi)實(shí)驗(yàn)的作液，建議您現(xiàn)現(xiàn)配，當(dāng)天使；澄清的儲備液可以根據(jù)儲存

3、條件，適當(dāng)保存；以下溶劑前的百分 指該溶劑在您配制終溶液中的體積占)：1. 請依序添加每種溶劑： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.08 mg/mL (4.05 mM); Clear solution2. 請依序添加每種溶劑： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.08 mg/mL (4.05 mM); Clear solution3. 請依序添加每種溶劑： 10% DMSO 90% corn oil1/3 Master of Small Molecules

4、 您邊的抑制劑師www.MedChemESolubility: 2.08 mg/mL (4.05 mM); Clear solutionBIOLOGICAL ACTIVITY物活性 CCT196969種泛-Raf 抑制劑，抑制 B-Raf，BRafV600E 和 CRAF，IC50 分別為 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)體外研究 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.體內(nèi)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 您邊的抑制劑師www.MedChemECell. 2015 Jan 12;27(1):85-96.McePdfHeightCaution: Product has not be