CNS penetrant TEAD1,2,4 inhibitor MSC-4070 derived from phenotypic screening hit optimization

30-149 nM), with selectivity for TEAD1,2,4 over TEAD3. Our findings indicate that while molecular weight and TPSA influence CNS penetration, efflux transporter interactions are more predictive of brain exposure. MSC-4070 represents a promising candidate for targeting TEAD-driven tumors in the central nervous system.