| 名称 | AV-412 free base |
| 描述 | AV-412 free base is an EGFR inhibitor (IC50s: 0.75, 0.79, 0.5, 2.3, 19 nM for EGFR, EGFR(T790M), EGFR(L858R), EGFR(L858R/T790M) and ErbB2). |
| 细胞实验 | To test the effects of AV-412 on growth factor-dependent cell proliferation, A431 and A7r5 cells are cultured for 24 h at 37°C in the presence of 1 ng/mL epidermal growth factor and 50 ng/mL platelet-derived growth factor, respectively. The 3H-thymidine incorporation during this period is measured. |
| 激酶实验 | Recombinant intracellular kinase domains of EGFR, EGFRL858R, EGFRT790M, EGFRL858R/T790M, and purified EGFR from A431 cell membranes are used. Kinase reactions are carried out in 8 mM MOPS (pH 7.0), 0.2 mM ethylenediaminetetraacetic acid (EDTA), 10 mM MnCl2, 10 mM Mg acetate, 0.1 mg/mL poly(Glu, Tyr) 4:1, [γ33P-ATP], and 5–10 mU of enzyme, except that 250 μM of the GGMEDIYFEFMGGKKK peptide substrate is used for EGFRT790M. Phosphorylation is initiated by the addition of ATP and is allowed to proceed for 40 min at room temperature. The reaction is stopped by the addition of 3% phosphoric acid, then aliquots of the reaction mixture are spotted onto a filter mat. After rinsing to remove peptides bound non-specifically, the filter is scintillation counted. |
| 动物实验 | For studies examining the dosing schedule in relation to efficacy against TE-8 tumors, AV-412 is administered either once daily, every other day, or once per week for 2 weeks. Mice are killed 1 day after the final treatment, and the tumors are dissected and weighed. For evaluation of tumor phosphorylation, tumor-bearing mice are given a single administration of AV-412 and tumors are dissected 4 h later. |
| 体外活性 | AV-412 free base 可抑制EGFR和ErbB2的自磷酸化（IC50：分别为43和282 nM）。AV-412 还抑制 EGF 依赖性细胞增殖（IC50：100 nM）。AV-412 free base 在gefitinib耐药的 H1975 细胞系中可阻断 EGFR 信号传导，该细胞系携带 EGFR 的 L858R 和 T790M 双突变。 |
| 体内活性 | 在癌症异种移植模型中，AV-412 free base （30 mg/kg）能完全抑制分别过表达EGFR和ErbB2的A431和BT-474细胞系的肿瘤生长。AV-412在与其抗肿瘤功效相对应的剂量下，可抑制EGFR和ErbB2的自磷酸化。在采用不同的给药方案时，AV-412 free base 在每日给药和隔日给药方案下均表现出显著效果，但在每周一次的给药方案下则未见显著效果。此外，AV-412 free base 对gefitinib耐药的ErbB2过表达乳腺癌KPL-4细胞系也表现出显著的抗肿瘤效果。 |
| 存储条件 | Powder: -20°C for 3 years | In solvent: -80°C for 1 year
Shipping with blue ice/Shipping at ambient temperature. |
| 溶解度 | 10% DMSO+40% PEG300+5% Tween-80+45% Saline : 2 mg/mL (3.94 mM), Sonication is recommended.
DMSO : 48 mg/mL (94.67 mM), Sonication is recommended.
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| 关键字 | MP-412 | MP412 | MP 412 | EGFR (wt), EGFR (T790M), EGFR (L858R), EGFR (L858R/T790M ) | AV-412 free base | AV412 free base | AV-412 | AV412 | AV 412 free base | AV 412 |
| 相关产品 | Neratinib | Lapatinib | Chalcone | Gefitinib | Erlotinib | Erlotinib hydrochloride | Osimertinib | Trastuzumab | Afatinib | Lidocaine Hydrochloride hydrate | Genistein | Brigatinib |