4-(3-氯-4-氟苯基氨基)-7-甲氧基-6-[3-(4-吗啉基)丙氧基]喹唑啉盐酸盐

中文名称:

4-(3-氯-4-氟苯基氨基)-7-甲氧基-6-[3-(4-吗啉基)丙氧基]喹唑啉盐酸盐

中文同义词:

盐酸吉非替尼;4-(3-氯-4-氟苯基氨基)-7-甲氧基-6-[3-(4-吗啉基)丙氧基]喹唑啉盐酸盐;吉非替尼盐酸盐;吉非替尼原料药;EGFR酪氨酸激酶抑制剂;GEFITINIB盐酸盐

英文名称:

4-(3-Chloro-4-fluorophenylamino)-7-methoxy-6-[3-(4-morpholinyl)propoxy]quinazoline hydrochloride

英文同义词:

Gefitinib hydrochloride (ZD-1839 hydrochloride);4-(3-Chloro-4-fluorophenylamino)-7-methoxy-6-[3-(4-morpholinyl)propoxy]quinazoline hydrochloride;Gefitinib hydrochloride;Gefitinib Hcl;ZD-1839 hydrochloride;Iressa hydrochloride;Gefitinib hydrochloride salt

CAS号:

184475-55-6

分子式:

C22H24ClFN4O3.HCl

分子量:

483.37

EINECS号:

1533716-785-6

相关类别:

抗肿瘤药物;医药中间体;细胞生物学试剂

Mol文件:

184475-55-6.mol

生物活性

Gefitinib hydrochloride (ZD1839 hydrochloride) 是一种有效，选择性和口服活性的 EGFR 酪氨酸激酶抑制剂，IC50 为 33 nM。Gefitinib hydrochloride 选择性抑制 EGF 刺激的肿瘤细胞生长 (IC50 为 54 nM)，并阻断 EGF 刺激的肿瘤细胞中 EGFR 自磷酸化。Gefitinib hydrochloride 还可诱导细胞自噬 (autophagy)，并具有抗肿瘤活性。

靶点

Target Value EGFR (Cell-free assay) 15.5 nM EGFR (858R/T790M) (Cell-free assay) 823.3 nM

Target

Value

EGFR (Cell-free assay)

15.5 nM

EGFR (858R/T790M) (Cell-free assay)

823.3 nM

体外研究

Gefitinib (0.01-0.1 mM) results in increased phosphotyrosine load of the receptor, increased signalling to ERK and stimulation of proliferation and anchorage-independent growth, presumably by inducing EGFRvIII dimerisation in long-term exposure of EGFRvIII-expressing cells. On the other hand, gefitinib (1-2 mM) significantly decreases EGFRvIII phosphotyrosine load, EGFRvIII-mediated proliferation and anchorage-independent growth. Gefitinib (ZD1839) inhibits the monolayer growth of these EGF-driven untransformed cells with IC 50 of 20 nM. Gefitinib leads to an inhibition of CALU-3 and GLC82 cell proliferation, with an IC 50 of 2 μM.

体内研究

Gefitinib (150 mg/kg, p.o.) in conbination with Metformin induces a significant reduction in tumor growth in nude mice bearing H1299 or CALU-3 GEF-R cells that are grown subcutaneously as tumor xenografts. In irradiated rats, Gefitinib treatment augmentes lung inflammation, including inflammatory cell infiltration and pro-inflammatory cytokine expression, while Gefitinib treatment attenuates fibrotic lung remodeling due to the inhibition of lung fibroblast proliferation.