ATP-binding cassette (ABC) transporters are pivotal for cell detoxification and survival. Overexpression of ABC transporter in tumor cells lead to chemoresistance through the efflux of chemotherapeutic agents. P-glycoprotein (Pgp/ABCB1), multidrug resistance protein 1 (MRP1/ABCC1) and breast cancer resistance protein (BCRP/ABCG2) are the major ABC transporters involved in multidrug resistance (MDR) of cancer cells against anticancer drugs. ABCG2 is one of the major transporters involved in the efflux of different cytotoxic agents. Hence, inhibition of ABCG2-mediated transport is considered a prime target to resist MDR of cancer cells. Here, brief structural biology and functions of ABCG2 were discussed with the aim to identify key pharmacophoric elements to design potent and selective as well as non-toxic ABCG2 inhibitors. Structure-inhibition relationships (SIRs) of the earlier reported compounds were also explored. Taken together, this study offers insight for further development of ABCG2 inhibitors.

ATP 结合盒 (ABC) 转运蛋白对于细胞解毒和存活至关重要。肿瘤细胞中 ABC 转运蛋白的过表达通过化疗药物的流出导致化疗耐药。P-糖蛋白 (Pgp/ABCB1)、多药耐药蛋白 1 (MRP1/ABCC1) 和乳腺癌耐药蛋白 (BCRP/ABCG2) 是参与癌细胞对抗癌药物的多药耐药 (MDR) 的主要 ABC 转运蛋白。ABCG2 是参与不同细胞毒剂流出的主要转运蛋白之一。因此，抑制 ABCG2 介导的转运被认为是抵抗癌细胞 MDR 的主要目标。在这里，简要讨论了 ABCG2 的结构生物学和功能，旨在确定关键的药效团元素，以设计有效的、选择性的以及无毒的 ABCG2 抑制剂。还探索了早期报道的化合物的结构-抑制关系 (SIR)。总之，这项研究为进一步开发 ABCG2 抑制剂提供了见解。