KRM-62146

KRM-62146 is a chemically synthesized small-molecule inhibitor designed to target transcriptional enhancer factor TEF-3 (TEAD4), a terminal transcriptional effector of the Hippo-YAP/TAZ signaling pathway [1]. Developed by the Korea Institute of Radiological and Medical Sciences (KIRAMS), KRM-62146 is designed to achieve antitumor efficacy while minimizing potential toxicity associated with broad blockade of YAP-mediated signaling [1]. In preclinical studies, the compound demonstrated TEAD-dependent transcriptional inhibition, reduced TEAD4 cellular target engagement, and decreased expression of downstream effectors CYR61 and CTGF [1]. It has shown metabolic stability in liver microsomes and preclinical antitumor activity in H226 and HCT116 xenograft models [1].