EGFR-IN-2

SKU: orb1709791

Description

EGFR-IN-2 is an orally bioavailable, mutation-selective EGFR inhibitor designed for NSCLC research. It potently targets T790M resistance mutants (IC50 27-33 nM) while sparing wild-type EGFR (IC50 218 nM). This profile supports its investigation in preclinical models for overcoming tyrosine kinase inhibitor resistance.

Research Area

Cell Biology

Key Properties

• CAS Number: 1643497-70-4
• MW: 551.66
• Purity: 99.79% (May vary between batches)
• Formula: C₂₆H₃₃N₉O₃S
• SMILES: [C@@H](CC)(C)N1N=C(C=2C1=CC(NC3=NC(=NC=C3)C4=CN(S(=O)(=O)C5CC5)N=C4)=NC2)N6CC(C(C)(C)O)C6
• Target: EGFR

Bioactivity

• Target IC50:
  H1975 cells (T790M/L858R):0.027 μM|PC9 cells (del746–750):0.033 μM|PC9-ER cells (T790M/del746–750):0.008 μM
• In Vivo:
  In a H1975 xenograft mouse model, EGFR-IN-2 was evaluated for in vivo target engagement and pharmacokinetics. After oral administration at 50 mg/kg, free plasma concentrations remained above the in vitro IC₅₀ (0.027 μM) for up to 8 hours; at 100 mg/kg, this duration extended to 16 hours. Corresponding suppression of phosphorylated EGFR, ERK1/2, and AKT confirmed effective target inhibition in vivo. The EGFR-IN-2 exhibited moderate plasma clearance in mice (104 mL/min/kg) with 19% oral bioavailability, and in dogs, clearance was 13 mL/min/kg with 30% bioavailability.
• In Vitro:
  EGFR-IN-2 (Compound 21) demonstrated excellent inhibitory activity in various EGFR-mutant NSCLC cell lines. Inhibition of EGFR autophosphorylation was evaluated in H1975 (T790M/L858R), PC9-ER (T790M/del746–750), and PC9 (del746–750) cell lines, with IC₅₀ values of 0.027 μM, 0.008 μM, and 0.033 μM respectively. In a kinase panel of 225 kinases, only 12 were inhibited >70% at 0.1 μM, demonstrating high target specificity. EGFR-IN-2 exhibited low clearance in human liver microsomes and hepatocytes (3.8 and 2.7 mL/min/kg, respectively), and good predicted oral bioavailability .

Storage & Handling

• Storage: store at low temperature,keep away from moisture | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

EGFRIN2, EGFR, EGFR IN 2

Compound Identifiers

PubChem CID

121595975