Department of Pharmaceutical Sciences, Dr. Harisingh Gour University, Sagar, Madhya Pradesh, India.
Natural Science Laboratory, Division of Medicinal and Pharmaceutical Chemistry, Department of Pharmaceutical Technology, Jadavpur University, Kolkata, West Bengal, India; Department of Pharmaceutical Technology, JIS University, 81, Nilgunj Road, Agarpara, Kolkata, West Bengal, India.
Eur J Med Chem. 2022 Nov 5;241:114628. doi: 10.1016/j.ejmech.2022.114628. Epub 2022 Jul 31.
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.
三磷酸腺苷结合盒（ABC）转运蛋白对于细胞解毒和存活至关重要。肿瘤细胞中 ABC 转运蛋白的过度表达会通过排出化疗药物导致化疗耐药。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）是与癌细胞对抗癌药物的多药耐药性（MDR）相关的主要 ABC 转运蛋白。ABCG2 是参与不同细胞毒性药物外排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。本文简要讨论了 ABCG2 的结构生物学和功能，旨在确定设计有效、选择性和非毒性 ABCG2 抑制剂的关键药效团元素。还探讨了先前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 抑制剂提供了思路。
