EGFR-IN-176 

EGFR-IN-176 is an orally active and ATP-competitive EGFR mutant inhibitor (particularly C797S-mediated EGFR triple mutant). EGFR-IN-176 demonstrates highly selective inhibition of the growth of triple-mutant cells including Ba/F3 EGFR^{19del/T790M/C797S} (IC₅₀ = 0.001 nM) and Ba/F3 EGFR^{L858R/T790M/C797S} (IC₅₀ = 0.04 nM). EGFR-IN-176 effectively inhibits subsequent AKT signaling in Ba/F3 and PC-9 cells expressing EGFR^{19del/T790M/C797S} or EGFR^{L858R/T790M/C797S}. EGFR-IN-176 selectively inhibits EGFR signaling in cell lines harboring EGFR triple mutation and shows no inhibitory effect against A431 cells that express wild-type EGFR. EGFR-IN-176 can effectively inhibit the enzymatic activity of ALK (IC₅₀ < 0.5 nM). EGFR-IN-176 effectively inhibits tumor growth in mouse experiments and shows good anti-nonsmall cell lung cancer (NSCLC) ^[1].

EGFR-IN-176 (Compound 31r, 0.0045 nM-10,000 nM, 48 h) exhibits extremely potent and selective growth inhibitory activity against cells harboring EGFR triple mutation in vitro, including Ba/F3 EGFR19del/T790M/C797S (IC50 = 0.001 nM) and Ba/F3 EGFRL858R/T790M/C797S (IC50 = 0.04 nM), with low cytotoxicity towards wild-type EGFR cells A431 (IC50 > 10,000 nM)^[1].
EGFR-IN-176 (500 nM, 7 days) inhibits PC-9 EGFR19del/T790M/C797S and PC-9 EGFRL858R/T790M/C797S proliferation in the short term and deprives cancer cells of their self-renewal and clonogenic growth capabilities in the long term^[1].
EGFR-IN-176 (250 nM, 0-24 h) can effectively inhibit the migration ability of PC-9 EGFR19del/T790M/C797S and PC-9 EGFRL858R/T790M/C797S ^[1].
EGFR-IN-176 (500 nM, 48 h) can induce PC-9 EGFR19del/T790M/C797S and PC-9 EGFRL858R/T790M/C797S apoptosis^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

EGFR-IN-176 (40-80 mg/kg, i.g., once daily for 21 days) can dose-dependently significantly inhibit or even promote tumor regression in PC-9 xenograft mice^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

699.87

C₃₅H₄₅N₁₁O₃S

2754394-10-8

O=S(N(C)C1=C2N=CC=NC2=CC=C1NC3=C4C=CNC4=NC(NC5=C(OC)C=C(N6CCC(CC6)N7CCN(CC7)C)C(CC)=C5)=N3)(C)=O

Room temperature in continental US; may vary elsewhere.

Please store the product under the recommended conditions in the Certificate of Analysis.

• [1]. Wu Z, et al. Discovery of Potent and Selective Pyrrolo[2,3-d]pyrimidine Derivatives as Fourth-Generation EGFR Inhibitors Targeting Triple Mutation. J Med Chem. 2025 Sep 25;68(18):19205-19228.  [Content Brief]