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Abstract：
The mortality rate in patients suffering from non-small cell lung cancer (NSCLC) is quite high. This type of cancer mainly occurs due to rearrangements in the anaplastic lymphoma kinase (ALK) gene which leads to form an oncogene of fused gene NPM-ALK. Brigatinib is recently approved by FDA in April 2017 as a potent tyrosine kinase inhibitor (TKI) for the NSCLC therapy. In the present scenario, it is no less than a wonder drug because it is indicated for the treatment of advanced stages of metastatic ALK positive NSCLC, a fatal disease to overcome the resistance of various other ALK inhibitors such as crizotinib, ceritinib and alectinib. In addition to ALK, it is also active against multiple types of kinases such as ROS1, Insulin like growth factor-1Receptor and EGFR. It can be synthesized by using N-[2-methoxy-4-[4-(dimethylamino) piperidin-1-yl] aniline] guanidine and 2,4,5-trichloropyrimidine respectively in two different ways. Its structure consists of mainly dimethylphosphine oxide group which is responsible for its pharmacological activity. It is active against various cell lines such as HCC78, H2228, H23, H358, H838, U937, HepG2 and Karpas- 299. Results of ALTA (ALK in Lung Cancer Trial of AP26113) phase ½ trial shows that 90 mg of brigatinib for 7 days and then 180 mg for next days is effective in the treatment of NSCLC. Brigatinib has been shown to have favorable risk benefit profile and is a safer drug than the available cytotoxic chemotherapeutic agents. In comparison to other FDA approved drugs for the same condition, it causes fewer minor adverse reactions which can be easily managed either by changing the dose or by providing good supportive care. This article is intended to provide readers with an overview of chemistry, pharmacokinetic, pharmacodynamic and safety profile of brigatinib, which addresses an unmet medical need.
摘要：
患有非小细胞肺癌(NSCLC)的患者的死亡率相当高。这种类型的癌症主要是由于间变性淋巴瘤激酶（ALK）基因的重排而发生的，该重排导致形成融合基因NPM-ALK的癌基因。Brigatinib最近于2017年4月被FDA批准为用于NSCLC治疗的有效酪氨酸激酶抑制剂（TKI）。在目前的情况下，它不亚于一种神奇的药物，因为它适用于治疗晚期转移性ALK阳性NSCLC，一种致命的疾病，以克服各种其他ALK抑制剂如克唑替尼的耐药性，ceritinib和alectinib。除了ALK,它还对多种类型的激酶如ROS1，胰岛素样生长因子-1受体和EGFR具有活性。它可以通过分别使用N-[2-甲氧基-4-[4-（二甲基氨基）哌啶-1-基]苯胺]胍和2,4,5-三氯嘧啶以两种不同的方式合成。其结构主要由负责其药理活性的二甲基氧化膦基团组成。它对各种细胞系如HCC78、H2228、H23、H358、H838、U937、HepG2和Karpas-299具有活性。ALTA（AP26113肺癌试验中的ALK）1/2期试验的结果表明，90mg布格替尼7天，然后180mg第二天有效治疗NSCLC。布吉替尼已被证明具有有利的风险益处,并且是比可用的细胞毒性化学治疗剂更安全的药物。与其他FDA批准的相同条件的药物相比，它引起的轻微不良反应较少，可以通过改变剂量或提供良好的支持治疗来轻松管理。本文旨在为读者提供化学概述，药代动力学，布格替尼的药效学和安全性，解决了未满足的医疗需求。
