Abstract：
Cancer, characterized by uncontrolled cell growth and metastasis, is responsible for nearly one in six deaths and represents a severe threat to public health worldwide. Chemotherapy can substantially improve the quality of life and survival of patients with cancer, but anticancer chemotherapeutics are associated with a range of adverse effects. Moreover, almost all currently available anticancer chemotherapeutics could develop drug resistance over a period of time of application in cancer patients and ultimately lead to cancer relapse and death in 90% of patients, creating an urgent need to develop new anticancer agents. Fused pyrimidines trait the inextricable part of DNA and RNA and are vital in numerous biological processes. Fused pyrimidines can act on various biological cancer targets and have the potential to address drug resistance. In addition, more than 20 fused pyrimidines have already been approved for clinical treatment of different cancers and occupy a prominent place in the current therapeutic arsenal, revealing that fused pyrimidines are privileged scaffolds for the development of novel anticancer chemotherapeutics. The purpose of this review is to summarize the current scenario of fused pyrimidines with in vivo anticancer therapeutic potential along with their acute toxicity, metabolic profiles as well as pharmacokinetic properties, toxicity and mechanisms of action developed from 2020 to the present to facilitate further rational exploitation of more effective candidates.
摘要：
癌症,以不受控制的细胞生长和转移为特征，造成近六分之一的死亡，对全球公共卫生构成严重威胁。化疗可以大大提高癌症患者的生活质量和生存率，但是抗癌化学疗法与一系列不良反应有关。此外，几乎所有目前可用的抗癌化学疗法都可以在癌症患者的一段时间内产生耐药性，并最终导致90％的患者癌症复发和死亡，迫切需要开发新的抗癌剂。融合嘧啶是DNA和RNA不可分割的部分，在许多生物过程中至关重要。融合嘧啶可以作用于各种生物癌症靶标，并具有解决耐药性的潜力。此外,超过20种融合嘧啶已经被批准用于不同癌症的临床治疗，并在当前的治疗武器库中占有重要地位，揭示了融合嘧啶是开发新型抗癌化学疗法的特权支架。这篇综述的目的是总结具有体内抗癌治疗潜力的融合嘧啶及其急性毒性的当前情况。代谢谱以及药代动力学特性，从2020年到现在发展起来的毒性和作用机制，以促进进一步合理利用更有效的候选物。
