Avitinib maleate是一种基于吡咯并嘧啶的不可逆表皮生长因子受体（EGFR）抑制剂，其IC50值为7.68nM。
Cas No.:1557268-88-8
Sample solution is provided at 25 µL, 10mM.
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Avitinib maleate is a pyrrolopyrimidine-based irreversible epidermal growth factor receptor (EGFR) inhibitor with an IC50 of 7.68nM[1]. Avitinib maleate is also a BTK inhibitor that induces apoptosis and inhibits phosphorylation of BTK in mantle cell lymphoma[2]. Avitinib maleate is usually used in research on non-small cell lung cancer (NSCLC) and acute myeloid leukemia (AML)[3][4].
In vitro, Avitinib maleate (2.5 and 5μM; 12 days) impairs CFU-MK formation and inhibits the proliferation of CD34+ HSC-derived MK progenitor cells[5].
In vivo, pretreated with Avitinib maleate (30mg/kg/day; orally; 7 days) inhibited the metabolic activity of CYP450 enzymes, and significantly increased the AUC(0-∞) of probe substrates phenacetin, bupropion, and dextromethorphan in rats[6]. Avitinib maleate (30mg/kg/day; orally; 7 days) inhibited the metabolic activity of osimertinib, significantly increased the AUC and MRT of osimertinib, and decreased CLz/F in rats[7].
References:
[1] Xu X, Mao L, Xu W, et al. AC0010, an Irreversible EGFR Inhibitor Selectively Targeting Mutated EGFR and Overcoming T790M-Induced Resistance in Animal Models and Lung Cancer Patients. Mol Cancer Ther. 2016;15(11):2586-2597.
[2] Yan X, Zhou Y, Huang S, et al. Promising efficacy of novel BTK inhibitor AC0010 in mantle cell lymphoma. J Cancer Res Clin Oncol. 2018;144(4):697-706.
[3] Wang H, Pan R, Zhang X, Si X, Wang M, Zhang L. Abivertinib in patients with T790M-positive advanced NSCLC and its subsequent treatment with osimertinib. Thorac Cancer. 2020;11(3):594-602.
[4] Huang S, Pan J, Jin J, et al. Abivertinib, a novel BTK inhibitor: Anti-Leukemia effects and synergistic efficacy with homoharringtonine in acute myeloid leukemia. Cancer Lett. 2019;461:132-143.
[5] Huang J, Huang X, Li Y, et al. Abivertinib inhibits megakaryocyte differentiation and platelet biogenesis. Front Med. 2022;16(3):416-428.
[6] Shi Y, Meng D, Wang S, et al. Effects of Avitinib on CYP450 Enzyme Activity in vitro and in vivo in Rats. Drug Des Devel Ther. 2021;15:3661-3673.
[7] Wu Q, Jiang H, Wang S, et al. Effects of avitinib on the pharmacokinetics of osimertinib in vitro and in vivo in rats. Thorac Cancer. 2020;11(10):2775-2781.
Avitinib maleate是一种基于吡咯并嘧啶的不可逆表皮生长因子受体（EGFR）抑制剂，其IC50值为7.68nM[1]。Avitinib maleate也是一种BTK抑制剂，能够诱导套细胞淋巴瘤中的细胞凋亡并抑制BTK的磷酸化[2]。Avitinib maleate通常用于非小细胞肺癌（NSCLC）和急性髓系白血病（AML）的研究[3][4]。
在体外实验中，Avitinib maleate（2.5和5μM；12天）损害CD34+ HSC来源的MK祖细胞的CFU-MK的形成并抑制细胞增殖[5]。
在体内实验中，Avitinib maleate（30mg/kg/天；口服；连续7天）预处理可抑制大鼠CYP450酶的代谢活性，显著增加探针底物苯乙酸、布普品和右美沙芬的AUC(0-∞)[6]。Avitinib maleate（30mg/kg/天；口服；连续7天）可抑制奥希替尼的代谢活性，显著增加奥希替尼的AUC和MRT，同时降低CLz/F[7]。
| Cell experiment [1]: | |
Cell lines | CD34+ HSCs |
Preparation Method | Mononuclear cells were isolated by the Ficoll-Paque density gradient centrifugation. CD34+ HSCs were then isolated from mononuclear cells with anti-CD34-coupled immunomagnetic microbeads. CD34+ HSCs were cultured for two days in StemSpan SFEM II medium supplemented with SCF (100ng/mL) and IL-3 (2ng/mL) to encourage proliferation in a 12-well plate at 37°C in a 5% CO2 fully humidified atmosphere. IL-6 (20ng/mL), IL-9 (10ng/mL), and TPO (20ng/mL) were then added to the medium to induce MK differentiation, which was designated as day 0. CD34+ HSCs were treated with aAvitinib maleate or DMSO continuously from days 0 to 12 of culture prior to the study to determine the effect of Avitinib maleate on megakaryopoiesis. CD34+ HSCs (5×104) were seeded into 24-well plates in the semisolid MegaCultTM medium with cytokines and type I bovine collagen for 12 days. Culture slides were fixed and stained with anti-integrin αIIbβ3 antibodies. Cells were assigned to one of three treatment groups: 0 (control), 2.5, and 5μM Avitinib maleate. The total number of colonies visible under a microscope was scored by two independent evaluators. The CFU-MK-derived colony was defined as a cluster of five or more MKs. |
Reaction Conditions | 2.5 and 5μM; 12 days |
Applications | Avitinib maleate impairs CFU-MK formation of CD34+ HSC-derived MK progenitor cells. |
| Animal experiment [2]: | |
Animal models | Male Sprague-Dawley rats |
Preparation Method | ale SpragueDawley (SD) rats, body weight 220-250g were housed in a specific pathogen-free (SPF) facility under 12h light-dark cycles with access to rodent cubes and sterile water. Eighteen SPF-grade healthy male SD rats were randomly selected, divided into multiple-dose Avitinib maleate (Group A), single-dose Avitinib maleate group (Group B), and control group (Group C), with six rats each. Group A and Group B rats were orally administered 30mg/kg Avitinib maleate daily for seven days or on day seven only, respectively, while Group C rats were orally administered carboxymethyl cellulose sodium (CMC-Na) daily for seven days. In the seventh day, 30min later after oral administration of Avitinib maleate, the rats were intragastrically administered the six probe drugs simultaneously, including 1mg/kg tolbutamide and 10mg/kg each of phenacetin, bupropion, chlorzoxazone, dextromethorphan and midazolam. All rats were fasted for 12h before sampling. Blood was collected from the tail veins and collected directly into clean centrifuge tubes containing heparin. The samples were immediately centrifuged at 3000×g for 10min, the supernatant separated and transferred to another centrifuge tube, and the samples stored at -20°C until use. |
Dosage form | 30mg/kg/day; orally; 7 days |
Applications | Pretreated with Avitinib maleate inhibited the metabolic activity of CYP450 enzymes, and significantly increased the AUC(0-∞) of probe substrates phenacetin, bupropion, and dextromethorphan in rats. |
References: | |
| Cas No. | 1557268-88-8 | SDF | |
| 别名 | 艾维替尼马来酸盐; Abivertinib maleate; AC0010 maleate | ||
| Canonical SMILES | O=C(O)/C=C\C(O)=O.O=C(C=C)NC1=CC=CC(OC2=NC(NC3=CC(F)=C(N4CCN(C)CC4)C=C3)=NC5=C2C=CN5)=C1 | ||
| 分子式 | C30H30FN7O6 | 分子量 | 603.6 |
| 溶解度 | DMSO : ≥ 300 mg/mL (497.02 mM) | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.6567 mL | 8.2836 mL | 16.5673 mL |
| 5 mM | 331.3 μL | 1.6567 mL | 3.3135 mL |
| 10 mM | 165.7 μL | 828.4 μL | 1.6567 mL |
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| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
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| % DMSO % % Tween 80 % saline | ||||||||||
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计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
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2.
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