KS-3Ai

KS-3Ai is a potent, orally bioavailable small molecule pan-TEAD inhibitor developed by Kinnate Biopharma (now PharmaEssentia) to target the Hippo signaling pathway. The Hippo pathway is frequently dysregulated in various cancers, leading to the hyperactivation of transcriptional co-activators YAP and TAZ, which then bind to TEAD transcription factors to drive oncogenic gene expression. KS-3Ai functions by binding to the highly conserved palmitoylation pocket of TEAD1, TEAD2, TEAD3, and TEAD4. This binding prevents the auto-palmitoylation of TEAD proteins, a post-translational modification required for their structural stability and their productive interaction with YAP/TAZ. By disrupting the formation of the YAP/TAZ-TEAD transcriptional complex, KS-3Ai inhibits the transcription of genes associated with cell cycle progression, anti-apoptosis, and metastasis. It is primarily being investigated for the treatment of Hippo-pathway-driven malignancies, including NF2-deficient mesothelioma and other YAP/TAZ-dependent solid tumors.

Other names

KS3AiKS-3AiKS 3Aipan-TEAD inhibitor KS-3Ai