ISM6331 — Investigational Agent
TEAD Inhibitor · Phase 1 · Insilico Medicine
Mechanism of Action
ISM6331 is an orally bioavailable, AI-designed small-molecule pan-TEAD inhibitor that targets the Hippo signaling pathway. TEAD transcription factors (TEAD1–4) are the primary nuclear effectors of the Hippo pathway; when upstream Hippo kinase signaling (via MST1/2 → LATS1/2) is inactive — as occurs in malignant mesothelioma due to frequent biallelic loss of NF2, LATS1, or LATS2 — the oncoproteins YAP (Yes-associated protein) and TAZ (transcriptional coactivator with PDZ-binding motif, WWTR1) translocate to the nucleus and form transcriptional complexes with TEAD1–4, driving expression of…
Investigational Indications
- Unresectable malignant pleural mesothelioma in adult patients whose disease has progressed after anti-PD-1 therapy (with or without anti-CTLA-4) and platinum-based chemotherapy — FDA Fast Track Designation granted July 2026