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Publications

Journal Article Review Epublish

PubMed: 42540676 DOI: 10.2147/DDDT.S579368

Wise as a Serpent and Gentle as a Dove: Pharmacological Targeting of NRF2/KEAP1 Pathway from Treasure Trove of Mother Nature.

Drug Des Devel Ther 20:579368

Authors: Ammad Ahmad Farooqi, Sabit Zhussupov, Assiya Turgambayeva, Ubaidilla Datkhayev, Gulnara Kamalbekova, Natalya Latypova, Samal Duisekova, Baojun Xu

Affiliations

  • Department of Molecular Oncology, Institute of Biomedical and Genetic Engineering (IBGE), Islamabad, Pakistan.
  • Department of Surgery, Semey Medical University, Semey, 071400, Kazakhstan.
  • Department of Public Health and Management, Astana Medical University, Astana, 010000, Kazakhstan.
  • School of Pharmacy, Asfendiyarov Kazakh National Medical University, Almaty, 050012, Kazakhstan.
  • Department of Family Medicine, Astana Medical University, Astana, 010000, Kazakhstan.
  • Department of Public Health and Management, NJSC, Medical University Astana, Astana, Kazakhstan.
  • Food Science and Technology Program, Department of Life Sciences, Beijing Normal-Hong Kong Baptist University, Zhuhai, Guangdong, 519087, People's Republic of China.

Abstract

Discovery of NRF2 in 1994 was once assumed simplistic and classical but the following years witnessed phenomenal breakthroughs that led to a rapid increase in the components of complex molecular web. Emerging evidence has enabled us to develop a better understanding of the spatio-temporally placed molecular machinery both upstream and downstream to the NRF2 in different contexts and diseases. The exciting voyage to unravel the multifaceted roles of NRF2 in human diseases has catalyzed innovations in therapeutic approaches, inspiring the design of compounds for pharmacological modulation of NRF2 in disease prevention and intervention. In this review, we have set the spotlight on sketching a detailed landscape both upstream and downstream to the central signaling node of NRF2. Identification of the natural products having unique ability to pharmacologically target NRF2-associated networks. Later, we expand our discussion about ongoing and completed clinical trials related to multifaceted roles of NRF2 as an oncogene and a tumor suppressor. We argue that a holistic view of NRF2-driven upstream and downstream signaling is necessary for the identification of preventive or therapeutic opportunities.

MeSH

Mothers, Neoplasms, Drug Therapy, Neoplasm Metastasis, Carcinogenesis, Therapeutics, Apoptosis