EGFR T790M/L858R-IN-2

• CAT Number: I041372
• CAS Number: 2955607-40-4
• Molecular Formula: C28H28FN7O
• Molecular Weight: 497.57
• Purity: ≥95%
• Synonyms: N-[3-[[6-fluoro-2-[4-(4-methylpiperazin-1-yl)anilino]quinazolin-4-yl]amino]phenyl]prop-2-enamide
• InChI: InChI=1S/C28H28FN7O/c1-3-26(37)30-21-5-4-6-22(18-21)31-27-24-17-19(29)7-12-25(24)33-28(34-27)32-20-8-10-23(11-9-20)36-15-13-35(2)14-16-36/h3-12,17-18H,1,13-16H2,2H3,(H,30,37)(H2,31,32,33,34)
• InChIKey: KDWNVZXLHSMELQ-UHFFFAOYSA-N
• SMILES: CN1CCN(CC1)C2=CC=C(C=C2)NC3=NC4=C(C=C(C=C4)F)C(=N3)NC5=CC(=CC=C5)NC(=O)C=C

EGFR T790M/L858R-IN-2 is a potent and selective EGFRT790M/L858R inhibitor with IC50 values of 3.5, 1290 nM for EGFRT790M/L858R, EGFR WT, respectively. EGFR T790M/L858R-IN-2 decreases the expression of p-EGFR, P-AKT, P-ERK1/2. EGFR T790M/L858R-IN-2 induces Apoptosis and cell cycle arrest in the G1 phase. EGFR T790M/L858R-IN-2 shows anti-cancer activity[1].
EGFRT790M/L858R-IN-2 (compound 28f) (0.1, 1, 10 µM; 4 h) decreases the expression of p-EGFR, P-AKT, P-ERK1/2 in a dose-dependent manner in H1975, HCC827 cells[1].
EGFRT790M/L858R-IN-2 (0.1, 1, 10 µM; 48 h) induces apoptosis and cell cycle arrest in the G1 phase in H1975, HCC827 cells[1].
EGFRT790M/L858R-IN-2 (0.1, 1, 10 µM; 14 days) inhibits colony formation and cell migration in a dose-dependent manner[1].
EGFR T790M/L858R-IN-2 (5, 10, 20 mg/kg; i.p.; daily) inhibits tumor growth in a dose-dependent manner[1].
Pharmacokinetic Parameters of EGFR T790M/L858R-IN-2 in Male Sprague-Dawley rats[1].

parameter
i.v. (1 mg/kg)

T1/2 (h)
1.76 ± 0.65

Cmax (ng/mL)
649.90 ± 54.71

AUC0-t (h*ng/ml)
1036.86 ± 137.03

AUC0–∞ (h ng/ml)
1048.74 ± 134.39

Vz (mL/kg)
2515.40 ± 1184.92

CL(mL/min/kg)
16.07 ± 2.06

Male Sprague-Dawley rats, 1 mg/kg iv[1]

Reference

[1]. Pei J, et al. Design, Synthesis, and Antitumor Activity of Potent and Selective EGFR L858R/T790M Inhibitors and Identification of a Combination Therapy to Overcome Acquired Resistance in Models of Non-small-cell Lung Cancer. J Med Chem. 2023 Apr 27;66(8):5719-5752.
 [Content Brief]