Apatinib Mesylate Research Articles

甲磺酸阿帕替尼治疗一例肺腺癌脑转移患者的疗效分析

肺癌是世界上最常见也是恶性程度最高的恶性肿瘤之一，其致死率高居各类恶性肿瘤之首，五年生存率不足20%，其中非小细胞肺癌占其中70%以上，发现时多为晚期，非小细胞肺癌的5年生存率不足6%，患者可以通过选择放化疗得到疾病缓解和生存获益，仍有大部分患者会在末次化疗后的2到3个月内再次出现疾病的进展，特别是对于基因检测阴性的患者，对针对应用此类基因的靶向药物疗效不佳，研究发现新生血管为肿瘤生长提供氧和营养，促进肿瘤的生长，而血管内皮生长因子(VEGF)能激活下游通路刺激血管通过结合血管内皮细胞增生的表皮生长因子受体(VEGFR)，从而导致肿瘤的生长，抗血管生成药物通过抑制抑制血管生成能够抑制肿瘤发生发展和转移，甲磺酸阿帕替尼属于小分子抗血管生成抑制剂，作用于血管表皮生长因子酪氨酸激酶受体，通过抗血管生成来抑制实体肿瘤生长，甲磺酸阿帕替尼对于多线治疗失败的的非小细胞肺癌晚期治疗优确切的疗效，具有较好的耐受性。本文报道1例甲磺酸阿帕替尼作为四线药物治疗晚期非鳞NSCLC脑转移患者。 Lung cancer is one of the world’s most common and most malignant tumors. The lethality rate of which is the highest in all types of malignant tumors. The five-year survival rate of it is less than 20%, non-small cell lung cancer accounting for more than 70% of all cases and being diagnosed in the locally advanced stage. The 5-year survival rate of NSCLC is less than 6%. Patients can get relief and survival benefit by chemotherapy. Most patients will get PD in 2 or 3 months after the last chemotherapy, especially for those with negative genetic testing showing dismal efficacy to the application of molecular targeted drugs. Study found that neovascularization provide oxygen and nutrition for the growth of the tumor, to promote its growth. Anti-angiogenic drugs can inhibit tumor from progressing and metastasis by inhibiting angiogenesis. And the vascular epidermal growth factor (VEGF) can activate the downstream pathway to stimulate the proliferation of vessel endothelium via binding vascular epidermal growth factor receptor (VEGFR), thus leading to the growth of tumor. Paclitaxel mesylate is a small molecular anti-angiogenesis inhibitor. It can inhibit solid tumor growth factor tyrosine kinase receptor. Acid apatinib shows excellent efficacy and good tolerance for the advanced NSCLC whose multi-line treatment has been failed. This paper reports a case of apatinib mesylate as a fourth-line drug treatment in patients with advanced non-squamous NSCLC brain metastases.

Polymorphs and Hydrates of Apatinib Mesylate: Insight into the Crystal Structures, Properties, and Phase Transformations

Apatinib mesylate (ATM) is an orally administrated anticancer agent for the treatment of advanced gastric cancer. Single-crystal structures of four ATM solid forms, including two anhydrous polymorphs (I and II) and hydrates (HA and HB), were elucidated by single-crystal X-ray diffraction. The properties of these various forms were fully characterized by powder X-ray diffraction, differential scanning calorimetry, thermogravimetric analysis, Fourier transform-infrared spectroscopy, and Raman spectroscopy. The discrepant molecule conformations, H-bonding interactions, and packing arrangements in the crystal structures were analyzed associated with the hygroscopicity of forms I and II. Various form transformations induced by either moisture or solution conditions were examined, and the relative stability was established. The results revealed that HA is the most thermodynamically stable form and is superior to the currently marketed form.

A phase 1 trial of a potent and selective VEGF receptor inhibitor, apatinib, in patients with advanced solid tumors.

2525 Background: VEGF-mediated signaling pathways are critical to tumor growth. Apatinib mesylate is a novel, oral angiogenesis inhibitor that potently and selectively inhibits vascular endothelial...

Simultaneous determination of apatinib and its four major metabolites in human plasma using liquid chromatography–tandem mass spectrometry and its application to a pharmacokinetic study

Apatinib, also known as YN968D1, is a novel antiangiogenic agent that selectively inhibits vascular endothelial growth factor receptor-2. Currently, apatinib is undergoing phase II/III clinical trials in China for the treatment of solid tumors. Apatinib is extensively metabolized in humans, and its major metabolites in circulation include cis-3-hydroxy-apatinib (M1-1), trans-3-hydroxy-apatinib (M1-2), apatinib-25-N-oxide (M1-6), and cis-3-hydroxy-apatinib-O-glucuronide (M9-2). To investigate the pharmacokinetics of apatinib and its four major metabolites in patients with advanced colorectal cancer, a sensitive and selective liquid chromatography–tandem mass spectrometry method was developed and validated for the simultaneous determination of apatinib, M1-1, M1-2, M1-6, and M9-2 in human plasma. After a simple protein precipitation using acetonitrile as the precipitation solvent, all the analytes and the internal standard vatalanib were separated on a Zorbax Eclipse XDB C18 column (50mm×4.6mm, 1.8μm, Agilent) using acetonitrile: 5mmol/L ammonium acetate with 0.1% formic acid as the mobile phase with gradient elution. A chromatographic total run time of 9min was achieved. Mass spectrometry detection was conducted through electrospray ionization in positive ion multiple reaction monitoring modes. The method was linear over the concentration range of 3.00–2000ng/mL for each analyte. The lower limit of quantification for each analyte was 3.00ng/mL. The intra-assay precision for all the analytes was less than 11.3%, the inter-assay precision was less than 13.8%, and the accuracy was between −5.8% and 3.3%. The validated method was successfully applied to a clinical pharmacokinetic study following oral administration of 500mg apatinib mesylate in patients with advanced colorectal cancer.

YN968D1 is a novel and selective inhibitor of vascular endothelial growth factor receptor‐2 tyrosine kinase with potent activity in vitro and in vivo

Angiogenesis is an important process in cell development, especially in cancer. Vascular endothelial growth factor (VEGF) signaling is an important regulator of angiogenesis. Several therapies that act against VEGF signal transduction have been developed, including YN968D1, which is a potent inhibitor of the VEGF signaling pathway. This study investigated the antitumor activity of YN968D1 (apatinib mesylate) in vitro and in vivo. YN968D1 potently suppressed the kinase activities of VEGFR-2, c-kit and c-src, and inhibited cellular phosphorylation of VEGFR-2, c-kit and PDGFRβ. YN968D1 effectively inhibited proliferation, migration and tube formation of human umbilical vein endothelial cells induced by FBS, and blocked the budding of rat aortic ring. In vivo, YN968D1 alone and in combination with chemotherapeutic agents effectively inhibited the growth of several established human tumor xenograft models with little toxicity. A phase I study of YN968D1 has shown encouraging antitumor activity and a manageable toxicity profile. These findings suggest that YN968D1 has promise as an antitumor drug and might have clinical benefits.

Combine Apatinib Mesylate With PD-1 Antibody SHR-1210 for HCC With High Risk of Recurrence After Radical Resection

Combine Apatinib Mesylate With PD-1 Antibody SHR-1210 for HCC With High Risk of Recurrence After Radical Resection