CCT241161

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

CCT241161 是一种有效的泛 RAF 抑制剂，对 BRAF、V600E-BRAF 和 C-RAF 的 IC50 分别为 30、15 和 6 nM。

CCT241161 is a potent pan-RAF inhibitor with IC50 of 30, 15 and 6 nM for BRAF, V600E-BRAF and C-RAF, also potently inhibits SRC and LCK (IC50=10 and 3 nM, respectively).

CCT241161 (1, 3, 10, 30, 100 nM; 24 h) inhibits MEK and ERK in WM266.4 cells.CCT241161 (1, 10, 100 nM and 1, 10, 100 μM) inhibits BRAFV600E in Ba/F3 cells.CCT241161 (0.5 μM; 20 days) inhibits A375 cell but not cause drug resistance.CCT241161 (1 μM , 4 h) inhibits BRAF-inhibitor-resistant melanoma cells.CCT241161 (0.1, 0.3, 1, 3, 10 μM; 24 h) inhibits MEK in NRAS mutant cells.CCT241161 (0.1, 1, 10, 100 μM) shows anti-proliferative activity in D04 cells.Cell Viability Assay Cell Line:WM266.4 cells (BRAF mutant)Concentration:1, 3, 10, 30, 100 nM Incubation Time:24 h Result:Exhibited effects of inhibiting MEK and ERK in WM266.4 cells.Cell Viability Assay Cell Line:Ba/F3 cells Concentration:1, 10, 100 nM and 1, 10, 100 μM Incubation Time:Result:Inhibited BRAF-V600E and BRAF-T529N, V600E in Ba/F3 cells.Cell Viability Assay Cell Line:A375 cell Concentration:0.5 μM Incubation Time:20 days Result:Maintained inhibitory activity against A375 cell ,without drug resistance in 20 days.Cell Proliferation Assay Cell Line:D04 cells Concentration:0.1, 1, 10, 100 μM Incubation Time:Result:Efficiently inhibited NRAS mutant cell growth.Western Blot AnalysisCell Line:patient #2 (PLX4720-resistant cells from patient with vemurafenib-resistant melanoma) Concentration:1 μM Incubation Time:4 h Result:Inhibited MEK, ERK, and SRC in the cells from patient #2.Western Blot Analysis Cell Line:D04 cells Concentration:0.1, 0.3, 1, 3, 10 μM Incubation Time:24 h Result:Showed activity of surpressing MEK in NRAS mutant cells.

CCT241161 (10, 20 mg/kg; i.g; once a day for 7 days) inhibits the growth of BRAF mutant A375, PLX4720-resistant A375 and NRAS mutant DO4 tumor xenografts in mice. Animal Model:Female nude mice (5 to 6- week-old).Dosage:10, 20 mg/kg Administration:Oral gavage; once a day for 7 days.Result:Showed activity of tumor regression in nude mice with xenografts tumor of BRAF mutant A375, PLX4720-resistant A375 (A375/R) and NRAS mutant DO4, without causing any body weight loss to the mice.

CCT 241161

MAPK/ERK Signaling

Raf

Raf

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1163719-91-2

541.62

C28H27N7O3S

>98% (HPLC)

——

CSC1=CC(OC2=C3C(NC(C=N3)=O)=NC=C2)=CC=C1NC(NC4=CC(C(C)(C)C)=NN4C5=CC=CC=C5)=O

1-(3-(tert-butyl)-1-phenyl-1H-pyrazol-5-yl)-3-(2-(methylthio)-4-((3-oxo-3,4-dihydropyrido[2,3-b]pyrazin-8-yl)oxy)phenyl)urea

(-20℃)

With Ice Pack

≥ 2 years