Figure 1.

CCT196969 and CCT241161 Are BRAF Inhibitors

(A) Chemical structures of CCT196969 and CCT241161.

(B) Efficacy of PLX4720, CCT196969, and CCT241161 (1 μM) against a panel of 63 protein kinases. Color bar shows percent activity compared to DMSO.

(C) Phospho-MEK (pMEK), phospho-ERK (pERK), and ERK2 in WM266.4 and D35 cells treated for 24 hr with DMSO (D), CCT196969, or CCT241161.

(D) BRAF^V600E A375 cell proliferation assay (CellTiter Glo) with PLX4720, CCT196969, or CCT241161.

(E) BRAF^V600E A375 xenograft growth in nude mice treated with vehicle, CCT196969, or CCT241161 14 days after cell injection. ^∗∗∗p ≤ 0.001 (t test, two-tailed).

(F) BRAF^V600E and BRAF^T529N,V600E kinase inhibition by CCT196969 and CCT241161.

(G) Growth of Ba/F3 cells ([³H]-thymidine incorporation) expressing BRAF^V600E or BRAF^T529N,V600E treated with CCT196969 or CCT241161.

Bars represent SEM. See also Figure S1 and Tables S1–S3.