EGFR/C797S-IN-1

EGFR/C797S-IN-1 is a potent EGFR-C797S inhibitor with an IC50 value of 0.128 µM. EGFR/C797S-IN-1 shows anti-proliferative activity and anti-tumor activity. EGFR/C797S-IN-1 inhibits the expression of p-EGFR in a dose-dependent manner[1].

Research Areas >> Cancer

Signaling Pathways >> JAK/STAT Signaling >> EGFR

Signaling Pathways >> Protein Tyrosine Kinase/RTK >> EGFR

EGFRL858R/T790M/C797S:0.128 μM (IC50)

EGFR/C797S-IN-1 (compound 14d) (0-10 µM; 72 h) 显示抗增殖活性，对BaF3-EGFRL858R/T790M/C797S, BaF3-EGFR19del/T790M/C797S 的 IC50 值分别为 0.75、0.09 µM [1]。 EGFR/C797S-IN-1 (1-10000 nM; 24 h) 以剂量依赖性降低 p-EGFR、p-AKT、p-ERK 蛋白的表达[1]。 Cell Proliferation Assay[1] Cell Line: BaF3 cells with EGFRL858R/T790M/C797S and EGFR19del/T790M/C797S Mutations Concentration: 0-10 µM Incubation Time: 72 h Result: Showed anti-proliferative activitie with IC50s of 0.75, 0.09 µM for BaF3-EGFRL858R/T790M/C797S, BaF3-EGFR19del/T790M/C797S, respectively. Western Blot Analysis[1] Cell Line: BaF3-EGFRL858R/T790M/C797S, BaF3-EGFR19del/T790M/C797S cells Concentration: 1, 10, 100, 1000, 10000 nM Incubation Time: 24 h Result: Decreased the expression of p-EGFR, p-AKT. p-ERK protein in a dose dependent manner.

EGFR/C797S-IN-1 (10、30 mg/kg；每日一次，持续 14 天) 呈剂量依赖性显著降低小鼠体内的肿瘤生长[1]。 Animal Model: SD male rats[1] Dosage: 1 mg/kg for i.v.; 10 mg/kg for p.o. Administration: i.v. or p.o. Result: Displayed good biochemical activity and promising cellular activity. Animal Model: BALB/c nude mice (BaF3-EGFR19del/T790M/C797S xenograft model)[1] Dosage: 10, 30 mg/kg Administration: I.p.; daily for 14 days Result: Displayed an obvious suppressive effect of tumor growth, with the TGI at 51.36% and 67.95% at the dosage of 10 mg/kg and 30 mg/kg, respectively.

[1]. Dou D, et al. Discovery and optimization of 4-anilinoquinazoline derivatives spanning ATP binding site and allosteric site as effective EGFR-C797S inhibitors. Eur J Med Chem. 2022 Dec 15;244:114856.