VT03989

VT03989 is a potent, orally bioavailable small-molecule inhibitor of the TEA Domain (TEAD) transcription factors, which are the primary nuclear effectors of the Hippo signaling pathway. Developed by Vivace Therapeutics, VT03989 targets the Hippo-YAP/TAZ-TEAD axis, a pathway frequently dysregulated in various malignancies, including glioblastoma (GBM), mesothelioma, and other YAP/TAZ-dependent tumors. By inhibiting TEAD, the drug suppresses the expression of downstream oncogenic targets such as CTGF and CYR61, leading to reduced cell proliferation and increased apoptosis. Preclinical data presented at AACR 2024 demonstrated that VT03989 possesses favorable pharmacokinetics with significant brain and tumor penetration in patient-derived xenograft (PDX) models of glioblastoma, where it was well-tolerated and showed significant target modulation.

Other names

TEAD inhibitor VT3989