MAPK3 and neoplasm: Therefore, SKLB-D18 may exert anti-tumor activity and reverse the drug resistance by inducing ferroptosis.24 In addition, we found that it induced downregulation of platelet-derived growth factor receptors β (PDGFR-β), which was potentially associated with compensatory phosphorylation activation of ERK5 after ERK1/2 inhibition.17 Therefore, we speculated that SKLB-D18 could exert enhanced dual inhibition of ERK5 phosphorylation through direct inhibition of ERK5 and autophagic degradation of PDGFR-β, thus exerting excellent anti-drug resistance and anti-tumor activity (Supplementary Fig. S10).