| 生物活性 | CCT241161 is an orally active pan-RAFinhibitor withIC50s of 3, 6, 10, 15 and 30 nM forLCK,CRAF,SRC,V600E-BRAFandBRAF, respectively. CCT241161 shows good activity to inBRAFandNRASmutant melanomas. CCT241161 also exhibits anticancer cell proliferative activity[1]. |
体外研究
(In Vitro) | 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 BRAFV600Ein Ba/F3 cells[1].
CCT241161 (0.5 μM; 20 days) inhibits A375 cell but not cause 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. |
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体内研究
(In Vivo) | 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 causing any body weight loss to the mice. |
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