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

RSC Medicinal Chemistry 2026 Open access

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Authors: Timo Heinrich, Carl Petersson, Jakub Gunera, Alessia Gambardella, Daniel Schwarz, Sakshi Garg, Heike Schilke, Thomas Weitzel, Christian Kolb, Uwe Anlauf, Vivian Reither, Corinna Rettig
+7 more Beate Opelt, Andrea Delp, Nicole Wildner, Pedro M. F. Sousa, Filipe Freire, Tiago M. Bandeiras, Dirk Wienke
DOI: 10.1039/d5md00928f
Cited by: 2
References: 29

Abstract

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.

Fields of Study & Subjects

Hippo pathway signaling and YAP/TAZ Axon Guidance and Neuronal Signaling Wnt/β-catenin signaling in development and cancer

Publication details

Journal / source
RSC Medicinal Chemistry
Publisher
Royal Society of Chemistry (RSC)
Volume
17
Issue
3
Pages
1559–1572
Publication date
1 January 2026
Language
EN