Targeting epigenetic regulators to overcome drug resistance in cancers

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: Feb. 17, 2023

Abstract Drug resistance is mainly responsible for cancer recurrence and poor prognosis. Epigenetic regulation a heritable change in gene expressions independent of nucleotide sequence changes. As the common epigenetic mechanisms, DNA methylation, histone modification, non-coding RNA have been well studied. Increasing evidence has shown that aberrant regulations contribute to tumor resistance. Therefore, targeting regulators represents an effective strategy reverse drug In this review, we summarize roles addition, as essential factors modifications, demethylases mediate or genomic modifications. Herein, comprehensively describe functions demethylase family including lysine-specific family, Jumonji C-domain-containing arginine fully discuss their regulatory mechanisms related therapeutic strategies, small-molecule inhibitors small interfering overcome resistance, are also described.

Language: Английский

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Strategies to overcome cancer multidrug resistance (MDR) through targeting P-glycoprotein (ABCB1): An updated review

Pharmacology & Therapeutics, Journal Year: 2023, Volume and Issue: 249, P. 108488 - 108488

Published: July 11, 2023

Language: Английский

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Mechanism of multidrug resistance to chemotherapy mediated by P‑glycoprotein (Review)

International Journal of Oncology, Journal Year: 2023, Volume and Issue: 63(5)

Published: Aug. 28, 2023

Multidrug resistance (MDR) seriously limits the clinical application of chemotherapy. A mechanism underlying MDR is overexpression efflux transporters associated with chemotherapeutic drugs. P‑glycoprotein (P‑gp) an ATP‑binding cassette (ABC) transporter, which promotes by pumping out drugs and reducing their intracellular concentration. To date, P‑gp has been detected in various types chemoresistant cancer inhibiting P‑gp‑related suggested. The present review summarizes mechanisms mediated different tumors evaluated related signaling pathways, aim improving understanding current status P‑gp‑mediated resistance. This focuses on main MDR, providing a reference for study reversing MDR. first involves decreasing activity altering its conformation or hindering P‑gp‑chemotherapeutic drug binding. second inhibitory expression to reduce efflux. third knocking ABCB1 gene. Potential strategies that can inhibit include certain natural products, synthetic compounds biological techniques. It important screen lead candidate techniques inhibition, identify inhibitors targeting relevant pathways overcome

Language: Английский

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Simplified Derivatives of Tetrandrine as Potent and Specific P-gp Inhibitors to Reverse Multidrug Resistance in Cancer Chemotherapy

Journal of Medicinal Chemistry, Journal Year: 2023, Volume and Issue: 66(6), P. 4086 - 4105

Published: March 9, 2023

Targeted inhibition of a drug efflux transporter P-glycoprotein (P-gp) is an important strategy to reverse multidrug resistance in cancer chemotherapy. In this study, rationally structural simplification natural tetrandrine was performed based on molecular dynamics simulation and fragment growth, leading easily prepared, novel, simplified compound OY-101 with high reversal activity low cytotoxicity. Its excellent synergistic anti-cancer effect vincristine (VCR) against drug-resistant cells Eca109/VCR confirmed by assay, flow cytometry, plate clone formation synergism analysis (IC50 = 9.9 nM, RF 690). Further mechanism study that the specific efficient P-gp inhibitor. Importantly, increased VCR sensitization vivo without obvious toxicity. Overall, our findings may provide alternative for design novel inhibitor as anti-tumor chemotherapy sensitizer.

Language: Английский

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Design, synthesis, and bioactivity evaluation of novel indole-selenide derivatives as P-glycoprotein inhibitors against multi-drug resistance in MCF-7/ADR cell

European Journal of Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 268, P. 116207 - 116207

Published: Feb. 10, 2024

Language: Английский

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Spiroindoline quinazolinedione derivatives as inhibitors of P-glycoprotein: potential agents for overcoming multidrug resistance in cancer therapy

Molecular Diversity, Journal Year: 2025, Volume and Issue: unknown

Published: March 19, 2025

Language: Английский

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Molecular Modeling Strategies of Cancer Multidrug Resistance

Drug Resistance Updates, Journal Year: 2021, Volume and Issue: 59, P. 100789 - 100789

Published: Nov. 23, 2021

Language: Английский

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New drug approvals for 2021: Synthesis and clinical applications

European Journal of Medicinal Chemistry, Journal Year: 2022, Volume and Issue: 245, P. 114898 - 114898

Published: Nov. 4, 2022

Language: Английский

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Novel Benzo Five-Membered Heterocycle Derivatives as P-Glycoprotein Inhibitors: Design, Synthesis, Molecular Docking, and Anti-Multidrug Resistance Activity

Journal of Medicinal Chemistry, Journal Year: 2023, Volume and Issue: 66(8), P. 5550 - 5566

Published: April 3, 2023

A proposed strategy to overcome multidrug resistance (MDR) of anticancer drugs in chemotherapy is disable the efflux function P-glycoprotein (P-gp). In this study, based on ring-merging and fragment-growing strategies, 105 novel benzo five-membered heterocycle derivatives were designed, synthesized, screened. Exploration structure-activity relationship (SAR) led identification d7 with low cytotoxicity promising reversal activity doxorubicin MCF-7/ADR cells. Furthermore, mechanism studies revealed that stemmed from inhibition P-gp efflux. Molecular docking further clarified observed trends SAR displaying potent affinity P-gp. Additionally, coadministration achieved stronger antitumor a xenograft model than alone. These results suggest potential MDR reveal agent acting as inhibitor provides guidelines for future development new inhibitors.

Language: Английский

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Design, synthesis and biological evaluation of novel phenylfuran-bisamide derivatives as P-glycoprotein inhibitors against multidrug resistance in MCF-7/ADR cell

European Journal of Medicinal Chemistry, Journal Year: 2023, Volume and Issue: 248, P. 115092 - 115092

Published: Jan. 5, 2023

Language: Английский

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