TEAD Inhibitor BGC515

An orally bioavailable inhibitor of the transcription factor TEAD (TEA domain), with potential antineoplastic activity. Upon oral administration, TEAD inhibitor BGC515 targets, binds to and inhibits TEAD, thereby disrupting the interaction between the transcription co-activators yes-associated protein 1 (YAP)/transcriptional coactivator with PDZ-binding motif (TAZ) and TEAD. This may inhibit YAP/TAZ-TEAD-promoted transcription of multiple genes involved in tumor cell proliferation, progression and survival, and may result in enhanced apoptosis in TEAD-dependent cancers. Hippo pathway alterations, as seen in tumors with neurofibromatosis type 2 (NF2)-deficiency, large tumor suppressor 1 (LATS1) and 2 (LATS2) mutations and YAP/TAZ fusions, lead to Hippo pathway activation, hyperactivation of YAP/TAZ and activation of TEAD. It plays a key role in cancer initiation, progression, and cancer cell resistance to various therapies.