Gefitinib dihydrochloride (ZD 1839 dihydrochloride) 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 dihydrochloride 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 dihydrochloride还可诱导细胞自噬 (autophagy) 和凋亡 (apoptosis)，可用于癌症相关的研究，如肺癌和乳腺癌。
| 生物活性 | Gefitinib (ZD 1839) dihydrochloride is a potent, selective and orally activeEGFRtyrosine kinaseinhibitor with anIC50of 33 nM. Gefitinib dihydrochloride selectively inhibits EGF-stimulated tumor cell growth (IC50of 54 nM) and blocks EGF-stimulatedEGFRautophosphorylation in tumor cells. Gefitinib dihydrochloride also inducesautophagyand cellapoptosis, which can be used forcancerrelated research, such as Lungcancerand breastcancer[1][2][5]. |
| IC50& Target | IC50: 37 nM (Tyr1173 site, in NR6wtEGFR cells), 37 nM (Tyr992 site, in NR6wtEGFR cells)[1]. |
体外研究
(In Vitro) | Gefitinib dihydrochloride (0.01–0.1 μM, 72 h) results in increased phosphotyrosine load of the receptor, increased signalling to ERK and stimulation of proliferation and anchorage-independent growth[2].
Gefitinib dihydrochloride (1-2 μM, 72 h) significantly decreases EGFRvIII phosphotyrosine load, EGFRvIII-mediated proliferation and anchorage-independent growth[2].
Gefitinib dihydrochloride (0.62 μM, 24-72 h) inhibits IL-13-induced M2-like polarization of RAW 264.7 cells through the STAT6-dependent signaling pathway[3].
Gefitinib dihydrochloride (0.62 μM, 72 h) inhibits M2-like macrophage-promoted invasion and migration[3].
Gefitinib dihydrochloride (0-10 μM, 72 h) induces apoptosis (induction of BIM protein) in NSCLC Cell Lines (H3255 and HCC827 cells)[4].
Gefitinib dihydrochloride (100 nM, 24 h) suppresses macropinocytosis and increases the cellular uptake of extracellular vesicles( EVs) in HCC827 and A549 cells[6].
Gefitinib dihydrochloride (1.5-60 μM, 48 h) increases inhibition of proliferation in H358Rand A549Rcells (Cisplatin-resistant wtEGFR NSCLC cell lines)[7].
Western Blot Analysis[2] | Cell Line: | NR6wtEGFR, NR6W and NR6M | | Concentration: | 1, 10, 100 μM | | Incubation Time: | 5 h | | Result: | Inhibited EGFR tyrosine phosphorylations. |
Cell Migration Assay[3] | Cell Line: | LLCs cell | | Concentration: | 0.62 μM | | Incubation Time: | 72 h | | Result: | Abrogated M2-like macrophage promoted invasion and migration of LLCs. |
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体内研究
(In Vivo) | Gefitinib dihydrochloride (Oral administration, 75 mg/kg/d, 21 days) inhibits the M2-like polarization of macrophages in LLC mice metastasis model[3].
Gefitinib dihydrochloride (Oral administration, 75 mg/kg for the initial week, daily for 5 consecutive days per week) eliminates phosphorylation of HER2 and HER3 and signaling through MAPK and Akt in lobular hyperplasias and carcinomas, increases MAPK activity and cytokine production in splenocytes and lymph nodes[5].
Gefitinib dihydrochloride (Oral gavage, 150 mg/kg, daily) enhances the anti-tumor effect of Cisplatin in H358Rxenograft[7].
| Animal Model: | LLC mice metastasis model[3] | | Dosage: | 75 mg/kg/d, for 21 days. | | Administration: | Oral administration | | Result: | Reduced the number of lung metastasis nodules, down-regulated the expression of M2 marker genes and the percentages CD206+and CD68+macrophages in tumor tissues. |
| Animal Model: | BALB-NeuT transgenic mouse model[5] | | Dosage: | 75 mg/kg for the initial week, and increased by 15 mg/kg every other week, daily for 5 consecutive days per week, followed by 2 days without treatment and repeated for 8–9 weeks. | | Administration: | Oral administration | | Result: | Reduced tumor multiplicity from 9.6 to 0.58 (83%), and reduced the number and size of lobules and lobular nodules in treated mice. |
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| 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. |
