EGFR-IN-44

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EGFR-IN-44 

EGFR-IN-44 (Compound 6a) 是一种有效的、具有口服活性的 EGFR tyrosine kinase 抑制剂，其 IC50 值为 4.11 nM。EGFR-IN-44 诱导细胞凋亡 (apoptosis)，口服生物利用度为33.57%。EGFR-IN-44 可以用于非小细胞肺癌的研究。

EGFR-IN-44

EGFR-IN-44 Chemical Structure

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生物活性

EGFR-IN-44 (Compound 6a) is a potent, orally active EGFR tyrosine kinase inhibitor with an IC50 of 4.11 nM. EGFR-IN-44 induces cell apoptosis and shows an oral bioavailability value of 33.57%. EGFR-IN-44 can be studied for non-small-cell lung cancers[1].

IC50 & Target

IC50: 0.26 nM (EGFR T790M/L858R), 1.33 nM (EGFR L858R), 4.11 nM (EGFR)[1]
体外研究
(In Vitro)

EGFR-IN-44 (Compound 6a) (0-10 µM, 72 h) shows anti-proliferative activities against tumor cell lines[1].
EGFR-IN-44 binds to the ATP binding site of EGFR[1].
EGFR-IN-44 (0-10 nM, 48 h) induces H1975 cell apoptosis via the mitochondrial pathway, arrests cell cycle in G0/G1 phase, and suppresses cell migration[1].
EGFR-IN-44 (0-10 nM, 48 and 72h) shows hypotoxicity against normal cells[1].

Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.

Cell Proliferation Assay[1]

Cell Line: H1975 (EGFRT790M/L858R), PC9 (EGFRdel19), and H292 (EGFRWT)
Concentration: 0-10 µM
Incubation Time: 72 h
Result: Showed anti-proliferative activities with IC50 values of 0.0022 ± 0.001, 0.0048 ± 0.001, and 4.499 ± 0.057 µM against H1975, PC9, and H292 cells, respectively.

Apoptosis Analysis[1]

Cell Line: H1975
Concentration: 1, 5, and 10 nM
Incubation Time: 48 h
Result: Effectively induced cell apoptosis in a dose-dependent manner. Resulted in 33.7%, 52.4%, and 56.2% apoptosis at 1, 5, and 10 µM, respectively, compared to 5.81% apoptosis in the control group.

Western Blot Analysis[1]

Cell Line: H1975
Concentration: 5, 10, and 25 nM
Incubation Time: 48 h and 72 h
Result: Dose-dependently upregulated the expression levels of the proapoptotic proteins Bad and Bax and downregulated the expression level of the antiapoptotic protein Bcl-2. Sufficiently reduced the phosphorylation of EGFR and AKT.

Cell Cycle Analysis[1]

Cell Line: H1975
Concentration: 5 nM
Incubation Time: 0, 12, 24, or 48 h
Result: Exhibited a significant increase in the G0/G1 cell population and a dramatic decrease in G2/M phase.

Cell Cytotoxicity Assay[1]

Cell Line: LO2, HK2, HLF, and 293A
Concentration: 0.1, 1, 5, and 10 µM
Incubation Time: 48 h and 72 h
Result: Showed hypotoxicity with IC50 values of 7.247, 4.586, 3.787, and 2.925 µM against LO2, HK2, HLF, and 293A cells, respectively. The cell morphology was changed compared to the control.

体内研究
(In Vivo)

EGFR-IN-44 (Compound 6a) (25 mg/kg; i.g.; daily, 7days) shows strong antitumor activity without obvious toxicity[1].

Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model: Male BALB/c nude mice (5 weeks old, 18 – 20 g), H1975 xenograft model[1]
Dosage: 25 mg/kg
Administration: Intragastric administration, daily, 7 days
Result: Showed strong tumor inhibition (TGI = 90.24%) without obvious toxicity.
Animal Model: Male Sprague–Dawley (SD) rats[1]
Dosage: 1 mg/kg and 5 mg/kg
Administration: Intravenous injection and oral administration (Pharmacokinetic Analysis)
Result: In Vivo PK parameters of EGFR-IN-44 [1]

Parameters
Dose(mg/kg)		 EGFR-IN-44
5 (po)		 1 (iv)
t1/2 (h) 8.60 ± 1.8 1.42 ± 0.1
Tmax (h) 4.00 ± 0.002 /
Cmax (ng/mL) 80.40 ± 2.7 /
Vz F_pred (L/kg) 220.80 ± 41.2 6.83 ± 08
AUC0-t (H.ng/mL) 490.41 ± 29.9 291.91 ± 38.2
AUC0-∞ (H.ng/mL) 491.02 ± 44.2 295.76 ± 38.8
MRT0-last (h) 7.93 ± 0.8 1.35 ± 01
CL (mL/h/kg) 17.79 ± 3.9 3.12 ± 0.4
F(%) 33.57 ± 5.9 /


F = (AUC0-inf-PO × DOSEIV)/(AUC0-inf-IV × DOSE PO)*100%.

分子量

537.08

Formula

C27H29ClN6O2S
运输条件

Room temperature in continental US; may vary elsewhere.
储存方式

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

  • [1]. Baijiao An, et al. Novel third-generation pyrimidines-based EGFR tyrosine kinase inhibitors targeting EGFR T790M mutation in advanced non-small cell lung cancer. Bioorg Chem. 2022 May;122:105743.

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