PMID- 24393720 OWN - NLM STAT- MEDLINE DCOM- 20141124 LR - 20220311 IS - 1464-3391 (Electronic) IS - 0968-0896 (Print) IS - 0968-0896 (Linking) VI - 22 IP - 2 DP - 2014 Jan 15 TI - Retinoic acid signaling pathways in development and diseases. PG - 673-83 LID - S0968-0896(13)00956-5 [pii] LID - 10.1016/j.bmc.2013.11.025 [doi] AB - 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. CI - Copyright (c) 2013 Elsevier Ltd. All rights reserved. FAU - Das, Bhaskar C AU - Das BC AD - 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. FAU - Thapa, Pritam AU - Thapa P AD - 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. FAU - Karki, Radha AU - Karki R AD - 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. FAU - Das, Sasmita AU - Das S AD - 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. FAU - Mahapatra, Sweta AU - Mahapatra S AD - 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. FAU - Liu, Ting-Chun AU - Liu TC AD - Department of Surgery, Weill Cornell Medical College of Cornell University, New York, NY 10065, USA. FAU - Torregroza, Ingrid AU - Torregroza I AD - Department of Surgery, Weill Cornell Medical College of Cornell University, New York, NY 10065, USA. FAU - Wallace, Darren P AU - Wallace DP AD - The Kidney Institute, Department of Internal Medicine, Kansas University Medical Center, Kansas City, KS 66103, USA. FAU - Kambhampati, Suman AU - Kambhampati S AD - 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. FAU - Van Veldhuizen, Peter AU - Van Veldhuizen P AD - 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. FAU - Verma, Amit AU - Verma A AD - Albert Einstein College of Medicine, Bronx, NY 10461, USA. FAU - Ray, Swapan K AU - Ray SK AD - Department of Pathology, Microbiology, and Immunology, University of South Carolina School of Medicine, Columbia, SC 29209, USA. FAU - Evans, Todd AU - Evans T AD - Department of Surgery, Weill Cornell Medical College of Cornell University, New York, NY 10065, USA. Electronic address: tre2003@med.cornell.edu. LA - eng GR - HL56182/HL/NHLBI NIH HHS/United States GR - AI093220/AI/NIAID NIH HHS/United States GR - R56 AI093220/AI/NIAID NIH HHS/United States GR - R01 HL111400/HL/NHLBI NIH HHS/United States GR - AA020630/AA/NIAAA NIH HHS/United States GR - R01 DK081579/DK/NIDDK NIH HHS/United States GR - HL111400/HL/NHLBI NIH HHS/United States GR - R37 HL056182/HL/NHLBI NIH HHS/United States GR - R21 AA020630/AA/NIAAA NIH HHS/United States GR - R01 HL056182/HL/NHLBI NIH HHS/United States GR - DK081579/DK/NIDDK NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PT - Review DEP - 20131122 PL - England TA - Bioorg Med Chem JT - Bioorganic & medicinal chemistry JID - 9413298 RN - 5688UTC01R (Tretinoin) SB - IM MH - Aging/drug effects MH - Animals MH - Drug Discovery MH - Eye/chemistry/drug effects/*metabolism MH - Humans MH - Kidney/chemistry/drug effects/*metabolism MH - Metabolic Diseases/drug therapy/*metabolism MH - Molecular Structure MH - Neoplasms/chemistry/drug therapy/*metabolism/pathology MH - *Signal Transduction MH - Tretinoin/chemistry/*metabolism/pharmacology PMC - PMC4447240 MID - NIHMS553509 OTO - NOTNLM OT - Boron retinoids OT - Chemical biology OT - Nuclear receptors OT - Retinoic acid OT - Retinoids OT - Retinoids imaging OT - Vitamin A EDAT- 2014/01/08 06:00 MHDA- 2014/12/15 06:00 PMCR- 2015/05/28 CRDT- 2014/01/08 06:00 PHST- 2013/09/03 00:00 [received] PHST- 2013/11/04 00:00 [revised] PHST- 2013/11/13 00:00 [accepted] PHST- 2014/01/08 06:00 [entrez] PHST- 2014/01/08 06:00 [pubmed] PHST- 2014/12/15 06:00 [medline] PHST- 2015/05/28 00:00 [pmc-release] AID - S0968-0896(13)00956-5 [pii] AID - 10.1016/j.bmc.2013.11.025 [doi] PST - ppublish SO - Bioorg Med Chem. 2014 Jan 15;22(2):673-83. doi: 10.1016/j.bmc.2013.11.025. Epub 2013 Nov 22.