尽管化疗药物在癌症治疗中的临床进展令人鼓舞,创新和开发新的有效抗癌候选药物仍然是一项具有挑战性的工作。据估计,2030年每年有1500万人死亡,作为全球公共卫生和卫生系统的真正危机,癌症越来越引起人们的警觉。因此,科学家开始引入创新的解决方案来控制癌症全球健康问题。在这个问题中有希望的策略之一是具有靶向癌症的两个或更多个药效团的多靶标或智能杂交体。这些合理化的杂合分子在癌症治疗中获得了极大的兴趣,因为它们能够同时抑制超过癌症途径或靶标而没有药物-药物相互作用并且具有较少副作用。这些杂种的一个重要例子,HDAC杂合抑制剂或称为多靶向HDAC抑制剂。HDAC抑制剂协同提高其他抗癌药物疗效的能力,HDAC抑制剂的易用性cap组修饰促使许多药物化学家创新和开发新一代HDAC杂合抑制剂。值得注意的是,在这短暂的时间里,有四种HDAC抑制剂杂种已经进入不同阶段的临床试验,用于治疗不同类型的血液和实体瘤,即;CUDC-101,CUDC-907,还有Domatinostat.这篇综述揭示了HDACIs与一种或多种其他癌症靶药效团的最新杂交体。设计的多靶标杂种包括拓扑异构酶抑制剂,激酶抑制剂,一氧化氮释放剂,抗雄激素,FLT3和JAC-2抑制剂,PDE5抑制剂,NAMPT抑制剂,蛋白酶抑制剂,BRD4抑制剂和其他靶标。这篇综述可能有助于研究人员开发和发现癌症治疗的新视野。
Despite the encouraging clinical progress of chemotherapeutic agents in cancer treatment, innovation and development of new effective anticancer candidates still represents a challenging endeavor. With 15 million death every year in 2030 according to the estimates, cancer has increased rising of an alarm as a real crisis for public health and health systems worldwide. Therefore, scientist began to introduce innovative solutions to control the cancer global health problem. One of the promising strategies in this issue is the multitarget or smart hybrids having two or more pharmacophores targeting cancer. These rationalized hybrid molecules have gained great interests in cancer treatment as they are capable to simultaneously inhibit more than cancer pathway or target without drug-drug interactions and with less side effects. A prime important example of these hybrids, the HDAC hybrid inhibitors or referred as multitargeting HDAC inhibitors. The ability of HDAC inhibitors to synergistically improve the efficacy of other anti-cancer drugs and moreover, the ease of HDAC inhibitors cap group modification prompt many medicinal chemists to innovate and develop new generation of HDAC hybrid inhibitors. Notably, and during this short period, there are four HDAC inhibitor hybrids have entered different phases of clinical trials for treatment of different types of blood and solid tumors, namely; CUDC-101, CUDC-907, Tinostamustine, and Domatinostat. This
review shed light on the most recent hybrids of HDACIs with one or more other cancer target pharmacophore. The designed multitarget hybrids include topoisomerase inhibitors, kinase inhibitors, nitric oxide releasers, antiandrogens, FLT3 and JAC-2 inhibitors, PDE5-inhibitors, NAMPT-inhibitors, Protease inhibitors, BRD4-inhibitors and other targets. This
review may help researchers in development and discovery of new horizons in cancer treatment.