STX-721

STX-721 is an orally active, irreversible, covalent EGFR exon 20 insertion (ex20ins) inhibitor that selectively targets ex20ins-mutant dynamic protein states. STX-721 potently inhibits the kinase activity of EGFR ex20ins mutants (NPG, ASV, SVD) . STX-721 inhibits phosphorylation of EGFR (pEGFR Y1068) and downstream ERK (pERK Thr202/Tyr204), and suppresses proliferation of ex20ins-mutant Ba/F3 cells and human NSCLC cell lines (NCI-H2073 ASV KI, CUTO-14 ASV) . STX-721 induces tumor regression in EGFR ex20ins-mutant PDX/CDX models. STX-721 can be used for the study of non-small cell lung cancer (NSCLC) harboring EGFR or HER2 ex20ins mutations[1][2].

Product Specifications

CAS Number

[2765525-82-2]

UNSPSC

12352005

Target

EGFR; ERK

Type

Reference compound

Related Pathways

JAK/STAT Signaling; MAPK/ERK Pathway; Protein Tyrosine Kinase/RTK; Stem Cell/Wnt

Applications

COVID-19-immunoregulation

Field of Research

Cancer

Assay Protocol

https://www.medchemexpress.com/stx-721.html

Purity

98.25

Solubility

DMSO : 100 mg/mL (ultrasonic)

Smiles

O=C(N1CCC[C@]1(C)C#CC2=C(C=CN=C2)C3=C(C4=C(N3)CCNC4=O)NC5=CC=CC(Cl)=C5OC)/C=C/CN(C)C

Molecular Formula

C32H35ClN6O3

Molecular Weight

587.11

References & Citations

[1]Pagliarini RA, et al. STX-721, a Covalent EGFR/HER2 Exon 20 Inhibitor, Utilizes Exon 20-Mutant Dynamic Protein States and Achieves Unique Mutant Selectivity Across Human Cancer Models. Clin Cancer Res. 2025 Jul 15;31 (14) :3002-3018. |[2]Milgram BC, et al. 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. J Med Chem. 2025 Feb 13;68 (3) :2403-2421.