IJMPD | Different Therapeutic Aspects of Peroxisomes Proliferator-Activated Receptors

Indexing and Abstracting

Different Therapeutic Aspects of Peroxisomes Proliferator-Activated Receptors

Abhishek Kumar , Chetna Jhagta , Shivali Singla , Sachin Goyal

International Journal of Medical, Pharmacy and Drug Research(IJMPD), Vol-3,Issue-3, May - June 2019, Pages 1-20 , 10.22161/ijmpd.3.3.1

Download | Downloads : 9 | Total View : 1276

Abstract:

Peroxisome proliferator-activated receptors (PPARs) was discovered in 1990 belong to the super family of steroid hormone receptors. Three subtypes of PPAR which have been identified so far- PPARα, PPARβ/δ, and PPARγ. Human peroxisome proliferator-activated receptors (hPPARs) were initially recognized as therapeutic targets for the development of drugs to treat metabolic disorders, such as diabetes and dyslipidemia but now they have been used in energy burning, dyslipidemia, diabetes, inflammation, Hepatic steatosis, liver cancer, diabetic neuropathy, atherosclerosis also. These are included in management of NIDDM, macrophage differentiation, adipose differentiation , anti-cancer, inhibition of TH2 cytokine production and rheumatoid arthritis. PPARβ/δ can use to treat Huntington’s disease, fertility, dyslipidemia. The functions of a third PPAR isoform and its potential as a therapeutic target are currently under investigation.

Keywords:

PPAR, Diabetes, Metabolic Disorder, rheumatoid arthritis etc.

References:

[1] Kota BP, Huang TH, Roufogalis BD. An overview on biological mechanisms of PPARs. Pharmacological Research. 2005 Feb 1;51(2):85-94.
[2] Kuwabara N, Oyama T, Tomioka D, Ohashi M, Yanagisawa J, Shimizu T, Miyachi H. Peroxisome proliferator-activated receptors (PPARs) have multiple binding points that accommodate ligands in various conformations: phenylpropanoic acid-type PPAR ligands bind to PPAR in different conformations, depending on the subtype. Journal of medicinal chemistry. 2012 Jan 10;55(2):893-902.
[3] Grygiel-Górniak B. Peroxisome proliferator-activated receptors and their ligands: nutritional and clinical implications-a review. Nutrition journal. 2014 Dec;13(1):17.
[4] Lazar MA. PPARγ, 10 years later. Biochimie. 2005 Jan 1;87(1):9-13.
[5] Pyper SR, Viswakarma N, Yu S, Reddy JK. PPARα: energy combustion, hypolipidemia, inflammation and cancer. Nuclear receptor signaling. 2010 Jan;8(1):nrs-08002.
[6] Viswakarma N, Jia Y, Bai L, Vluggens A, Borensztajn J, Xu J, Reddy JK. Coactivators in PPAR-regulated gene expression. PPAR research. 2010;2010.
[7] Larsen TM, Toubro S, Astrup A. PPARgamma agonists in the treatment of type II diabetes: is increased fatness commensurate with long-term efficacy?. International journal of obesity. 2003 Feb;27(2):147.
[8] Badr MZ, Youssef JA, editors. Peroxisome proliferator-activated receptors (PPARs): methods and protocols. Humana Press; 2013.
[9] Youssef JA, Badr MZ. Peroxisome proliferator-activated receptors: discovery and recent advances. Springer Science & Business Media; 2013 Apr 18.
[10] Wang N, Yin R, Liu Y, Mao G, Xi F. Role of peroxisome proliferator-activated receptor-γ in atherosclerosis. Circulation Journal. 2011;75(3):528-35.
[11] Willson TM, Brown PJ, Sternbach DD, Henke BR. The PPARs: from orphan receptors to drug discovery. Journal of medicinal chemistry. 2000 Feb 24;43(4):527-50.
[12] Balakumar P, Kadian S, Mahadevan N. Are PPAR alpha agonists a rational therapeutic strategy for preventing abnormalities of the diabetic kidney?. Pharmacological Research. 2012 Apr 1;65(4):430-6.
[13] Balakumar P, Arora MK, Singh M. Emerging role of PPAR ligands in the management of diabetic nephropathy. Pharmacological research. 2009 Sep 1;60(3):170-3.
[14] Dickey AS, Pineda VV, Tsunemi T, Liu PP, Miranda HC, Gilmore-Hall SK, Lomas N, Sampat KR, Buttgereit A, Torres MJ, Flores AL. PPAR-δ is repressed in Huntington's disease, is required for normal neuronal function and can be targeted therapeutically. Nature medicine. 2016 Jan;22(1):37.
[15] Moore KJ, Rosen ED, Fitzgerald ML, Randow F, Andersson LP, Altshuler D, Milstone DS, Mortensen RM, Spiegelman BM, Freeman MW. The role of PPAR-γ in macrophage differentiation and cholesterol uptake. Nature medicine. 2001 Jan;7(1):41.
[16] Yamamoto K, Tamura T, Henmi K, Kuboyama T, Yanagisawa A, Matsubara M, Takahashi Y, Suzuki M, Saito JI, Ueno K, Shuto S. Development of Dihydrodibenzooxepine Peroxisome Proliferator-Activated Receptor (PPAR) Gamma Ligands of a Novel Binding Mode as Anticancer Agents: Effective Mimicry of Chiral Structures by Olefinic E/Z-Isomers. Journal of Medicinal Chemistry. 2018 Oct 23;61(22):10067-83.
[17] Hsu WH, Lee BH, Hsu YW, Pan TM. Inhibition of Th2 cytokine production in T cells by monascin via PPAR-γ activation. Journal of agricultural and food chemistry. 2013 Aug 14;61(34):8126-33.
[18] Li XF, Sun YY, Bao J, Chen X, Li YH, Yang Y, Zhang L, Huang C, Wu BM, Meng XM, Li J. Functional role of PPAR-γ on the proliferation and migration of fibroblast-like synoviocytes in rheumatoid arthritis. Scientific reports. 2017 Oct 4;7(1):12671.
[19] Hsu WH, Lee BH, Pan TM. Monascin attenuates oxidative stress-mediated lung inflammation via peroxisome proliferator-activated receptor-gamma (PPAR-γ) and nuclear factor-erythroid 2 related factor 2 (Nrf-2) modulation. Journal of agricultural and food chemistry. 2014 Jun 3;62(23):5337-44.
[20] Boubia B, Poupardin O, Barth M, Binet J, Peralba P, Mounier L, Jacquier E, Gauthier E, Lepais V, Chatar M, Ferry S. Design, Synthesis, and Evaluation of a Novel Series of Indole Sulfonamide Peroxisome Proliferator Activated Receptor (PPAR) α/γ/δ Triple Activators: Discovery of Lanifibranor, a New Antifibrotic Clinical Candidate. Journal of medicinal chemistry. 2018 Feb 15;61(6):2246-65.
[21] Xu Y, Rito CJ, Etgen GJ, Ardecky RJ, Bean JS, Bensch WR, Bosley JR, Broderick CL, Brooks DA, Dominianni SJ, Hahn PJ. Design and synthesis of α-aryloxy-α-methylhydrocinnamic acids: a novel class of dual peroxisome proliferator-activated receptor α/γ agonists. Journal of medicinal chemistry. 2004 May 6;47(10):2422-5.
[22] Markt P, Petersen RK, Flindt EN, Kristiansen K, Kirchmair J, Spitzer G, Distinto S, Schuster D, Wolber G, Laggner C, Langer T. Discovery of novel PPAR ligands by a virtual screening approach based on pharmacophore modeling, 3D shape, and electrostatic similarity screening. Journal of medicinal chemistry. 2008 Sep 27;51(20):6303-17.
[23] Liu K, Xu L, Berger JP, MacNaul KL, Zhou G, Doebber TW, Forrest MJ, Moller DE, Jones AB. Discovery of a novel series of peroxisome proliferator-activated receptor α/γ dual agonists for the treatment of type 2 diabetes and dyslipidemia. Journal of medicinal chemistry. 2005 Apr 7;48(7):2262-5.
[24] Yu J, Ahn S, Kim HJ, Lee M, Ahn S, Kim J, Jin SH, Lee E, Kim G, Cheong JH, Jacobson KA. Polypharmacology of N 6-(3-Iodobenzyl) adenosine-5′-N-methyluronamide (IB-MECA) and Related A3 Adenosine Receptor Ligands: Peroxisome Proliferator Activated Receptor (PPAR) γ Partial Agonist and PPARδ Antagonist Activity Suggests Their Antidiabetic Potential. Journal of medicinal chemistry. 2017 Aug 28;60(17):7459-75.
[25] Xu Y, Etgen GJ, Broderick CL, Canada E, Gonzalez I, Lamar J, Montrose-Rafizadeh C, Oldham BA, Osborne JJ, Xie C, Shi Q. Design and synthesis of dual peroxisome proliferator-activated receptors γ and δ agonists as novel euglycemic agents with a reduced weight gain profile. Journal of medicinal chemistry. 2006 Sep 21;49(19):5649-52.
[26] Potterat O, Puder C, Wagner K, Bolek W, Vettermann R, Kauschke SG. Chlorocyclinones A− D, Chlorinated Angucyclinones from Streptomyces sp. Strongly Antagonizing Rosiglitazone-Induced PPAR-γ Activation. Journal of natural products. 2007 Nov 29;70(12):1934-8.
[27] Liu S, Su M, Song SJ, Hong J, Chung HY, Jung JH. An Anti-inflammatory PPAR-γ Agonist from the Jellyfish-derived Fungus Penicillium chrysogenum J08NF-4. Journal of natural products. 2018 Feb 1;81(2):356-63.
[28] Rudolph J, Chen L, Majumdar D, Bullock WH, Burns M, Claus T, Dela Cruz FE, Daly M, Ehrgott FJ, Johnson JS, Livingston JN. Indanylacetic Acid Derivatives Carrying 4-Thiazolyl-phenoxy Tail Groups, a New Class of Potent PPAR α/γ/δ Pan Agonists: Synthesis, Structure− Activity Relationship, and In Vivo Efficacy. Journal of medicinal chemistry. 2007 Mar 8;50(5):984-1000.
[29] Potterat O, Puder C, Wagner K, Bolek W, Vettermann R, Kauschke SG. Chlorocyclinones A− D, Chlorinated Angucyclinones from Streptomyces sp. Strongly Antagonizing Rosiglitazone-Induced PPAR-γ Activation. Journal of natural products. 2007 Nov 29;70(12):1934-8.
[30] Zhang X, Young HA. PPAR and immune system—what do we know?. International immunopharmacology. 2002 Jul 1;2(8):1029-44.
[31] Buscató EL, Blöcher R, Lamers C, Klingler FM, Hahn S, Steinhilber D, Schubert-Zsilavecz M, Proschak E. Design and synthesis of dual modulators of soluble epoxide hydrolase and peroxisome proliferator-activated receptors. Journal of medicinal chemistry. 2012 Nov 19;55(23):10771-5.
[32] Pirat C, Farce A, Lebègue N, Renault N, Furman C, Millet R, Yous S, Speca S, Berthelot P, Desreumaux P, Chavatte P. Targeting peroxisome proliferator-activated receptors (PPARs): development of modulators. Journal of medicinal chemistry. 2012 Feb 27;55(9):4027-61.
[33] Li JL, Xiao B, Park M, Yoo ES, Shin S, Hong J, Chung HY, Kim HS, Jung JH. PPAR-γ agonistic metabolites from the ascidian Herdmania momus. Journal of natural products. 2012 Nov 28;75(12):2082-7.
[34] Mahindroo N, Huang CF, Peng YH, Wang CC, Liao CC, Lien TW, Chittimalla SK, Huang WJ, Chai CH, Prakash E, Chen CP. Novel indole-based peroxisome proliferator-activated receptor agonists: design, SAR, structural biology, and biological activities. Journal of medicinal chemistry. 2005 Dec 29;48(26):8194-208.
[35] Nevin DK, Peters MB, Carta G, Fayne D, Lloyd DG. Integrated virtual screening for the identification of novel and selective peroxisome proliferator-activated receptor (PPAR) scaffolds. Journal of medicinal chemistry. 2012 May 24;55(11):4978-89.