title: Retinoic acid signaling pathways in development and diseases.
abstract: Retinoids comprise a group of compounds each composed of three basic parts: a trimethylated cyclohexene ring that is a bulky hydrophobic group, a conjugated tetraene side chain that functions as a linker unit, and a polar carbon-oxygen functional group. Biochemical conversion of carotenoid or other retinoids to retinoic acid (RA) is essential for normal regulation of a wide range of biological processes including development, differentiation, proliferation, and apoptosis. Retinoids regulate various physiological outputs by binding to nuclear receptors called retinoic acid receptors (RARs) and retinoid X receptors (RXRs), which themselves are DNA-binding transcriptional regulators. The functional response of RA and their receptors are modulated by a host of coactivators and corepressors. Retinoids are essential in the development and function of several organ systems; however, deregulated retinoid signaling can contribute to serious diseases. Several natural and synthetic retinoids are in clinical use or undergoing trials for treating specific diseases including cancer. In this review, we provide a broad overview on the importance of retinoids in development and various diseases, highlighting various retinoids in the drug discovery process, ranging all the way from retinoid chemistry to clinical uses and imaging.
authors.affiliation: Division of Hematology and Oncology, Department of Internal Medicine, Kansas University Medical Center, Kansas City, KS 66103, USA; Molecular Bio-nanotechnology, Imaging and Therapeutic Research Unit, Veteran Affairs Medical Center, Kansas City, MO 64128, USA; Department of Surgery, Weill Cornell Medical College of Cornell University, New York, NY 10065, USA; The Kidney Institute, Department of Internal Medicine, Kansas University Medical Center, Kansas City, KS 66103, USA. Electronic address: bdas@kumc.edu.
authors.forename: Bhaskar C
authors.initials: BC
authors.lastname: Das
authors.affiliation: Division of Hematology and Oncology, Department of Internal Medicine, Kansas University Medical Center, Kansas City, KS 66103, USA; Molecular Bio-nanotechnology, Imaging and Therapeutic Research Unit, Veteran Affairs Medical Center, Kansas City, MO 64128, USA.
authors.forename: Pritam
authors.initials: P
authors.lastname: Thapa
authors.affiliation: Division of Hematology and Oncology, Department of Internal Medicine, Kansas University Medical Center, Kansas City, KS 66103, USA; Molecular Bio-nanotechnology, Imaging and Therapeutic Research Unit, Veteran Affairs Medical Center, Kansas City, MO 64128, USA.
authors.forename: Radha
authors.initials: R
authors.lastname: Karki
authors.affiliation: Division of Hematology and Oncology, Department of Internal Medicine, Kansas University Medical Center, Kansas City, KS 66103, USA; Molecular Bio-nanotechnology, Imaging and Therapeutic Research Unit, Veteran Affairs Medical Center, Kansas City, MO 64128, USA.
authors.forename: Sasmita
authors.initials: S
authors.lastname: Das
authors.affiliation: Division of Hematology and Oncology, Department of Internal Medicine, Kansas University Medical Center, Kansas City, KS 66103, USA; Molecular Bio-nanotechnology, Imaging and Therapeutic Research Unit, Veteran Affairs Medical Center, Kansas City, MO 64128, USA.
authors.forename: Sweta
authors.initials: S
authors.lastname: Mahapatra
authors.affiliation: Department of Surgery, Weill Cornell Medical College of Cornell University, New York, NY 10065, USA.
authors.forename: Ting-Chun
authors.initials: TC
authors.lastname: Liu
authors.affiliation: Department of Surgery, Weill Cornell Medical College of Cornell University, New York, NY 10065, USA.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Torregroza
authors.affiliation: The Kidney Institute, Department of Internal Medicine, Kansas University Medical Center, Kansas City, KS 66103, USA.
authors.forename: Darren P
authors.initials: DP
authors.lastname: Wallace
authors.affiliation: Division of Hematology and Oncology, Department of Internal Medicine, Kansas University Medical Center, Kansas City, KS 66103, USA; Molecular Bio-nanotechnology, Imaging and Therapeutic Research Unit, Veteran Affairs Medical Center, Kansas City, MO 64128, USA.
authors.forename: Suman
authors.initials: S
authors.lastname: Kambhampati
authors.affiliation: Division of Hematology and Oncology, Department of Internal Medicine, Kansas University Medical Center, Kansas City, KS 66103, USA; Molecular Bio-nanotechnology, Imaging and Therapeutic Research Unit, Veteran Affairs Medical Center, Kansas City, MO 64128, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Van Veldhuizen
authors.affiliation: Albert Einstein College of Medicine, Bronx, NY 10461, USA.
authors.forename: Amit
authors.initials: A
authors.lastname: Verma
authors.affiliation: Department of Pathology, Microbiology, and Immunology, University of South Carolina School of Medicine, Columbia, SC 29209, USA.
authors.forename: Swapan K
authors.initials: SK
authors.lastname: Ray
authors.affiliation: Department of Surgery, Weill Cornell Medical College of Cornell University, New York, NY 10065, USA. Electronic address: tre2003@med.cornell.edu.
authors.forename: Todd
authors.initials: T
authors.lastname: Evans
mesh_terms: D000375:Aging / Q000187:drug effects; D000818:Animals; D055808:Drug Discovery; D005123:Eye / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D007668:Kidney / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D008659:Metabolic Diseases / Q000188:drug therapy / Q000378:metabolism*; D015394:Molecular Structure; D009369:Neoplasms / Q000737:chemistry / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction; D014212:Tretinoin / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D014212:Tretinoin
keywords: Boron retinoids; Chemical biology; Nuclear receptors; Retinoic acid; Retinoids; Retinoids imaging; Vitamin A