Journal Article

PUBDB-2025-04149

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Discovery of STX-721, a Covalent, Potent, and Highly Mutant-Selective EGFR/HER2 Exon20 Insertion Inhibitor for the Treatment of Non-Small Cell Lung Cancer

Milgram, B. C. (Corresponding author) ; Borrelli, D. R. ; Brooijmans, N. ; Henderson, J. A. ; Hilbert, B. J. ; Huff, M. R. ; Ito, T. ; Jackson, E. L. ; Jonsson, P. ; Ladd, B. ; O’Hearn, E. L. ; Pagliarini, R. A. ; Roberts, S. A. ; Ronseaux, S. ; Stuart, D. D. ; Wang, W. ; Guzman-Perez, A.

2025
ACS Washington, DC

This record in other databases:      

Please use a persistent id in citations: doi:10.1021/acs.jmedchem.4c02377  doi:10.3204/PUBDB-2025-04149

Abstract: After L858R and ex19del epidermal growth factor receptor (EGFR) mutations, ex20ins mutations are the third most common class of driver-mutations in non-small cell lung cancer (NSCLC). Unfortunately, first-, second-, and third-generation EGFR tyrosine kinase inhibitors (TKIs) are generally ineffective for ex20ins patients due to insufficient mutant activity and selectivity over wild-type EGFR, leading to dose-limiting toxicities. While significant advances in recent years have been made toward identifying potent EGFR ex20ins mutant inhibitors, mutant vs wild-type EGFR selectivity remains a significant challenge. STX-721 (53) is a potent, irreversible inhibitor of the majority of EGFR/HER2 ex20ins mutants and demonstrates excellent mutant vs wild-type selectivity both in vitro and in vivo. STX-721 is currently in phase 1/2 clinical trials for EGFR/HER2 ex20ins-driven NSCLC.

---

Contributing Institute(s):

1. EMBL-User (EMBL-User)

Research Program(s):

1. 6G3 - PETRA III (DESY) (POF4-6G3) (POF4-6G3)

Experiment(s):

1. PETRA Beamline P14 (PETRA III)

Appears in the scientific report 2025

---

Database coverage:
; ; ; BIOSIS Previews ; Biological Abstracts ; Chemical Reactions ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Ebsco Academic Search ; Essential Science Indicators ; Index Chemicus ; Nationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

---