| Identification | Back Directory | [Name]
(2E)-N-[4-[[3-Chloro-4-(2-pyridinylmethoxy)phenyl]amino]-7-(2-ethoxyethoxy)-6-quinazolinyl]-4-(dimethylamino)-2-butenamide | [CAS]
1879071-97-2 | [Synonyms]
(2E)-N-[4-[[3-Chloro-4-(2-pyridinylmethoxy)phenyl]amino]-7-(2-ethoxyethoxy)-6-quinazolinyl]-4-(dimethylamino)-2-butenamide | [Molecular Formula]
C30H33ClN6O4 | [MOL File]
1879071-97-2.mol | [Molecular Weight]
577.07 |
| Chemical Properties | Back Directory | [Boiling point ]
760.0±60.0 °C(Predicted) | [density ]
1.294±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted) | [pka]
11.96±0.43(Predicted) |
| Hazard Information | Back Directory | [Uses]
EGFR/HER2-IN-5 (compound 6h) is an orally active irreversible dual inhibitor. EGFR/HER2-IN-5 inhibits EGFR with an IC50 value of 1.01 nM and demonstrates potent EGFR kinase inhibitory activities on L858R and T790M mutations. EGFR/HER2-IN-5 has potent antitumor efficacy in vivo and can be used for lung cancer research[1]. | [in vivo]
EGFR/HER2-IN-5 (compound 6h) (oral gavage; 99.5 mg/kg, 24.9 mg/kg, 6.2 mg/kg; every other day or every day; 25 days) has good cancer suppression effect in a dose-dependent manner in the constructed NCI-H1975 tumor xenograft model[1]. | Animal Model: | BALB/c nude mice, female, 6–7 weeks of age with NCI-H1975 tumor xenograft[1] | | Dosage: | 99.5 mg/kg, 24.9 mg/kg, 6.2 mg/kg | | Administration: | Oral gavage; 99.5 mg/kg and 24.9 mg/kg for every other day for 25 days; 6.2 mg/kg for every day for 25 days | | Result: | Inhibited 84.11% of tumor xenografts growth at 99.5 mg/kg, 65.72% at 24.9 mg/kg, and 47% at 6.2 mg/kg in nude mice. |
| Animal Model: | BALB/c nude mice, female, 6-7 weeks of age with NCI-H1975 tumor xenograft[1] | | Dosage: | 10 mg/kg | | Administration: | Oral gavage; 10 mg/kg; 25 days | | Result: | The pharmacokinetic parameters of EGFR/HER2-IN-5 (compound 6h) oral (10 mg/kg) | Parameter | | | Oral Tmax | 8 h | | Cmax | 39.4 μg/L | | AUC0-a | 780 μg/L*h | | IV | 5 mg/kg | | half life | 4.9 h | | oral bioavailability | 28.8% |
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| [IC 50]
EGFR: 0.6 nM (IC50); HER2: 0.6 nM (IC50) | [References]
[1] Debasis Das, et.al. In vivo efficacy studies of novel quinazoline derivatives as irreversible dual EGFR/HER2 inhibitors, in lung cancer xenografts (NCI-H1975) mice models. Bioorg Chem. 2020 Jun;99:103790. DOI:10.1016/j.bioorg.2020.103790 |
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