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Biomolecules
Special Issues
Current Advances in ABC Transporters in Physiology and Disease
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Current Advances in ABC Transporters in Physiology and Disease

A special issue of Biomolecules (ISSN 2218-273X). This special issue belongs to the section "Molecular Biology".

Deadline for manuscript submissions: closed (31 March 2025) | Viewed by 4443

Special Issue Editor

Dr. Hiroshi Nakagawa

E-Mail Website
Guest Editor
Department of Applied Biological Chemistry, Graduate School of Bioscience and Biotechnology, Chubu University, Kasugai, Japan
Interests: ABC transporter; SNPs; drug resistance; disease; natural products
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

ATP-binding cassette (ABC) transporters are critical for transporting various endogenous metabolites such as bile acids, sterols, lipids, peptides, and exogenous molecules such as antibiotics, toxins, and drugs. Several studies in this field have revealed that several genes encoding these transporters are mutated in human diseases, several of which contribute to multidrug resistance in cancer chemotherapy, and that single nucleotide polymorphisms (SNPs) in these genes determine the pharmacokinetics of various drugs and contribute to the development of various diseases.

This Special Issue aims to present recent original research and review manuscripts that contribute to the understanding of ABC transporters, from their structure to their impact on human physiology, disease, and genetic variation, including the pathogenesis of multifactorial disorders such as metabolic diseases, drug pharmacokinetics, and multidrug resistance in cancer chemotherapy. This topic should enhance our understanding of ABC transporters, and pave the way for alternative therapeutic strategies and the development of preventive, diagnostic, and therapeutic approaches for some diseases.

Dr. Hiroshi Nakagawa
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomolecules is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • functions
  • structure
  • regulation
  • genetic polymorphisms

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Published Papers (2 papers)

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Research

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32 pages, 4364 KiB  
Article
Predictive and Prognostic Relevance of ABC Transporters for Resistance to Anthracycline Derivatives
by Rümeysa Yücer, Rossana Piccinno, Ednah Ooko, Mona Dawood, Gerhard Bringmann and Thomas Efferth
Biomolecules 2025, 15(7), 971; https://doi.org/10.3390/biom15070971 - 6 Jul 2025
Viewed by 344
Abstract
Anthracyclines have been clinically well established in cancer chemotherapy for decades. The main limitations of this drug class are the development of resistance and severe side effects. In the present investigation, we analyzed 30 anthracyclines in a panel of 59 cell lines of [...] Read more.
Anthracyclines have been clinically well established in cancer chemotherapy for decades. The main limitations of this drug class are the development of resistance and severe side effects. In the present investigation, we analyzed 30 anthracyclines in a panel of 59 cell lines of the National Cancer Institute, USA. The log10IC50 values varied from −10.49 M (3′-deamino-3′-(4″-(3″-cyano)morpholinyl)-doxorubicin, 1) to −4.93 M (N,N-dibenzyldaunorubicin hydrochloride, 30). Multidrug-resistant NCI-ADR-Res ovarian cancer cells revealed a high degree of resistance to established anthracyclines (between 18-fold to idarubicin (4) and 166-fold to doxorubicin (13) compared to parental, drug-sensitive OVCAR8 cells). The resistant cells displayed only low degrees of resistance (1- to 5-fold) to four other anthracyclines (7, 18, 28, 30) and were even hypersensitive (collaterally sensitive) to two compounds (1, 26). Live cell time-lapse microscopy proved the cross-resistance of the three chosen anthracyclines (4, 7, 9) on sensitive CCRF/CEM and multidrug-resistant CEM/ADR5000 cells. Structure–activity relationships showed that the presence of tertiary amino functions is helpful in avoiding resistance, while primary amines rather increased resistance development. An α-aminonitrile function as in compound 1 was favorable. Investigating the mRNA expression of 49 ATP-binding cassette (ABC) transporter genes showed that ABCB1/MDR1 encoding P-glycoprotein was the most important one for acquired and inherent resistance to anthracyclines. Molecular docking demonstrated that all anthracyclines bound to the same binding domain at the inner efflux channel side of P-glycoprotein with high binding affinities. Kaplan–Meier statistics of RNA sequencing data of more than 8000 tumor biopsies of TCGA database revealed that out of 23 tumor entities high ABCB1 expression was significantly correlated with worse survival times for acute myeloid leukemia, multiple myeloma, and hepatocellular carcinoma patients. This indicates that ABCB1 may serve as a prognostic marker in anthracycline-based chemotherapy regimens in these tumor types and a target for the development of novel anthracycline derivatives. Full article
(This article belongs to the Special Issue Current Advances in ABC Transporters in Physiology and Disease)
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Review

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26 pages, 3901 KiB  
Review
Structural View of Cryo-Electron Microscopy-Determined ATP-Binding Cassette Transporters in Human Multidrug Resistance
by Wenjie Fan, Kai Shao and Min Luo
Biomolecules 2024, 14(2), 231; https://doi.org/10.3390/biom14020231 - 17 Feb 2024
Cited by 9 | Viewed by 3347
Abstract
ATP-binding cassette (ABC) transporters, acting as cellular “pumps,” facilitate solute translocation through membranes via ATP hydrolysis. Their overexpression is closely tied to multidrug resistance (MDR), a major obstacle in chemotherapy and neurological disorder treatment, hampering drug accumulation and delivery. Extensive research has delved [...] Read more.
ATP-binding cassette (ABC) transporters, acting as cellular “pumps,” facilitate solute translocation through membranes via ATP hydrolysis. Their overexpression is closely tied to multidrug resistance (MDR), a major obstacle in chemotherapy and neurological disorder treatment, hampering drug accumulation and delivery. Extensive research has delved into the intricate interplay between ABC transporter structure, function, and potential inhibition for MDR reversal. Cryo-electron microscopy has been instrumental in unveiling structural details of various MDR-causing ABC transporters, encompassing ABCB1, ABCC1, and ABCG2, as well as the recently revealed ABCC3 and ABCC4 structures. The newly obtained structural insight has deepened our understanding of substrate and drug binding, translocation mechanisms, and inhibitor interactions. Given the growing body of structural information available for human MDR transporters and their associated mechanisms, we believe it is timely to compile a comprehensive review of these transporters and compare their functional mechanisms in the context of multidrug resistance. Therefore, this review primarily focuses on the structural aspects of clinically significant human ABC transporters linked to MDR, with the aim of providing valuable insights to enhance the effectiveness of MDR reversal strategies in clinical therapies. Full article
(This article belongs to the Special Issue Current Advances in ABC Transporters in Physiology and Disease)
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