MAPK

PLX7922, a RAF inhibitor, demonstrates binding affinity with BRAF V600E and exhibits inhibitory effects on pERK in BRAF V600E cell lines, while inducing pERK activation in mutant NRAS cell lines.

SKLB646 is an orally active multitarget kinase inhibitor that exhibits potent suppression of several kinases. It demonstrates significant inhibitory effects on SRC and VEGFR2, with IC50 values of 0.002 μmol/L and 0.012 μmol/L, respectively. Additionally, SKLB646 shows notable inhibition of B-Raf and C-Raf, with IC50 values of 0.022 μmol/L and 0.019 μmol/L, respectively. The compound inhibits the activation of the SRC signaling pathway and blocks the MAPK signaling pathway by inhibiting Raf kinases. Furthermore, SKLB646 inhibits the proliferation, migration, and invasion of human umbilical vein endothelial cells (HUVEC), thereby suppressing tumor-induced angiogenesis. SKLB646 also displays significant anti-proliferative and anti-survival effects on triple-negative breast cancer (TNBC) cell lines.

IHMT-RAF-128 is a potent pan-RAF inhibitor that demonstrates robust antitumor activity in xenograft mouse tumor models without causing significant toxicity.

WQ-C-401 is an orally active inhibitor of the platelet-derived growth factor receptor (PDGFR). It inhibits cell proliferation by blocking PDGFR auto-phosphorylation in a concentration-dependent manner, with EC50 values of 3.5 nM for PDGFRαY849 and 5.8 nM for PDGFRβY1021. Additionally, WQ-C-401 suppresses the proliferation and migration of PASMCs by inhibiting PDGF-BB-induced phosphorylation of ERK1/2, reduces collagen I synthesis, and increases α-SMA expression, thereby preventing pulmonary vascular remodeling. This compound shows promise for research in the field of pulmonary arterial hypertension.