CCT241161 是一种具有口服活性的泛型Raf抑制剂，其对LCK,CRaf,Src,V600E-BRaf和BRaf的IC50值分别为 3, 6, 10, 15 和 30 nM。CCT241161 在BRaf和NRas突变的黑色素瘤显示出良好的活性。CCT241161 还具有抗癌细胞增殖活性。

CCT241161 is an orally active pan- RAF inhibitor with IC 50 s of 3, 6, 10, 15 and 30 nM for LCK, CRAF, SRC, V600E-BRAF and BRAF, respectively. CCT241161 shows good activity to in BRAF and NRAS mutant melanomas. CCT241161 also shows anticancer cell proliferative activity [1].

CCT241161 (1, 3, 10, 30, 100 nM; 24 h) inhibits MEK and ERK in WM266.4 cells [1]. CCT241161 (1, 10, 100 nM and 1, 10, 100 μM) inhibits BRAF V600E in Ba/F3 cells [1]. CCT241161 (0.5 μM; 20 days) inhibits A375 cell without causing drug resistance [1]. CCT241161 (1 μM, 4 h) inhibits BRAF-inhibitor-resistant melanoma cells [1]. CCT241161 (0.1, 0.3, 1, 3, 10 μM; 24 h) inhibits MEK in NRAS mutant cells [1]. CCT241161 (0.1, 1, 10, 100 μM) shows anti-proliferative activity in D04 cells [1]. Cell Viability Assay [1] 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 [1] 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 [1] 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 [1] Cell Line: D04 cells Concentration: 0.1, 1, 10, 100 μM Incubation Time: Result: Efficiently inhibited NRAS mutant cell growth. Western Blot Analysis [1] Cell 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 [1] 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 [1]. Animal Model: Female nude mice (5 to 6- week-old) [1]. 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 resulting in body weight loss to the mice.

1163719-91-2

C28H27N7O3S

541.62

(< 1 mg/ml refers to the product slightly soluble or insoluble )
Powder: -20°C for 3 years
In solvent: -80°C for 2 years