STX-721

• Description :

  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].

• 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.

• Shipping Conditions :

  Room Temperature

• Storage Conditions :

  -20°C, 3 years; 4°C, 2 years (Powder)

• Scientific Category :

  Reference compound1

• Clinical Information :

  Phase 2

• CAS Number :

  [2765525-82-2]