Target Information
| Target General Information | Top | |||||
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| Target ID |
T36557
(Former ID: TTDC00069)
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| Target Name |
Peroxisome proliferator-activated receptor delta (PPARD)
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| Synonyms |
Peroxisomeproliferator-activated receptor beta; Peroxisomeproliferator activated receptor beta/delta; Peroxisome proliferator-activated receptor beta; PPARdelta; PPARB; PPAR-delta; PPAR-beta; Nuclear receptor subfamily 1 group C member 2; Nuclear hormone receptor 1; NUCI; NUC1; NR1C2
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| Gene Name |
PPARD
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| Target Type |
Clinical trial target
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[1] | ||||
| Disease | [+] 2 Target-related Diseases | + | ||||
| 1 | Non-alcoholic fatty liver disease [ICD-11: DB92] | |||||
| 2 | Obesity [ICD-11: 5B80-5B81] | |||||
| Function |
Receptor that binds peroxisome proliferators such as hypolipidemic drugs and fatty acids. Has a preference for poly-unsaturated fatty acids, such as gamma-linoleic acid and eicosapentanoic acid. Once activated by a ligand, the receptor binds to promoter elements of target genes. Regulates the peroxisomal beta-oxidation pathway of fatty acids. Functions as transcription activator for the acyl-CoA oxidase gene. Decreases expression of NPC1L1 once activated by a ligand. Ligand-activated transcription factor.
Click to Show/Hide
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| BioChemical Class |
Nuclear hormone receptor
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| UniProt ID | ||||||
| Sequence |
MEQPQEEAPEVREEEEKEEVAEAEGAPELNGGPQHALPSSSYTDLSRSSSPPSLLDQLQM
GCDGASCGSLNMECRVCGDKASGFHYGVHACEGCKGFFRRTIRMKLEYEKCERSCKIQKK NRNKCQYCRFQKCLALGMSHNAIRFGRMPEAEKRKLVAGLTANEGSQYNPQVADLKAFSK HIYNAYLKNFNMTKKKARSILTGKASHTAPFVIHDIETLWQAEKGLVWKQLVNGLPPYKE ISVHVFYRCQCTTVETVRELTEFAKSIPSFSSLFLNDQVTLLKYGVHEAIFAMLASIVNK DGLLVANGSGFVTREFLRSLRKPFSDIIEPKFEFAVKFNALELDDSDLALFIAAIILCGD RPGLMNVPRVEAIQDTILRALEFHLQANHPDAQYLFPKLLQKMADLRQLVTEHAQMMQRI KKTETETSLHPLLQEIYKDMY Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | AlphaFold | ||||
| HIT2.0 ID | T74WWP | |||||
| Drugs and Modes of Action | Top | |||||
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| Clinical Trial Drug(s) | [+] 6 Clinical Trial Drugs | + | ||||
| 1 | GFT-505 | Drug Info | Phase 3 | Non-alcoholic steatohepatitis | [2] | |
| 2 | MBX-8025 | Drug Info | Phase 2/3 | Obesity | [3] | |
| 3 | T3D-959 | Drug Info | Phase 1/2 | Alzheimer disease | [4] | |
| 4 | CER-002 | Drug Info | Phase 1 | Dyslipidemia | [5] | |
| 5 | KD3010 | Drug Info | Phase 1 | Obesity | [6] | |
| 6 | SAR351034 | Drug Info | Phase 1 | Dyslipidemia | [7] | |
| Discontinued Drug(s) | [+] 5 Discontinued Drugs | + | ||||
| 1 | GW-501516 | Drug Info | Discontinued in Phase 4 | Type-1 diabetes | [8], [9] | |
| 2 | GSK-677954 | Drug Info | Discontinued in Phase 2 | Non-alcoholic fatty liver disease | [10] | |
| 3 | Indeglitazar | Drug Info | Discontinued in Phase 2 | Type-2 diabetes | [11] | |
| 4 | Sodelglitazar | Drug Info | Discontinued in Phase 2 | Hyperlipidaemia | [12] | |
| 5 | CS-204 | Drug Info | Terminated | Metabolic disorder | [13] | |
| Preclinical Drug(s) | [+] 1 Preclinical Drugs | + | ||||
| 1 | KD-3020 | Drug Info | Preclinical | Non-alcoholic fatty liver disease | [10] | |
| Mode of Action | [+] 3 Modes of Action | + | ||||
| Modulator | [+] 5 Modulator drugs | + | ||||
| 1 | GFT-505 | Drug Info | [14] | |||
| 2 | T3D-959 | Drug Info | [16] | |||
| 3 | SAR351034 | Drug Info | [18] | |||
| 4 | GW-501516 | Drug Info | [1] | |||
| 5 | SAVX-1 | Drug Info | [30] | |||
| Agonist | [+] 14 Agonist drugs | + | ||||
| 1 | MBX-8025 | Drug Info | [15] | |||
| 2 | CER-002 | Drug Info | [17] | |||
| 3 | KD3010 | Drug Info | [6] | |||
| 4 | PMID25416646-Compound-Figure5-C | Drug Info | [19] | |||
| 5 | GSK-677954 | Drug Info | [10] | |||
| 6 | Indeglitazar | Drug Info | [20] | |||
| 7 | Sodelglitazar | Drug Info | [21] | |||
| 8 | KD-3020 | Drug Info | [10] | |||
| 9 | CS-204 | Drug Info | [22] | |||
| 10 | DB-900 | Drug Info | [24] | |||
| 11 | GW0742X | Drug Info | [26] | |||
| 12 | GW2433 | Drug Info | [27] | |||
| 13 | L-165041 | Drug Info | [28] | |||
| 14 | L-783483 | Drug Info | [28] | |||
| Inhibitor | [+] 6 Inhibitor drugs | + | ||||
| 1 | (11E)-OCTADEC-11-ENOIC ACID | Drug Info | [23] | |||
| 2 | GSK-0660 | Drug Info | [25] | |||
| 3 | GSK-3787 | Drug Info | [25] | |||
| 4 | Heptyl-Beta-D-Glucopyranoside | Drug Info | [23] | |||
| 5 | L-165461 | Drug Info | [29] | |||
| 6 | L-796449 | Drug Info | [29] | |||
| Chemical Structure based Activity Landscape of Target | Top |
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| Drug Property Profile of Target | Top | |
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| (1) Molecular Weight (mw) based Drug Clustering | (2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering | |
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| (3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering | (4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering | |
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| (5) Rotatable Bond Count (rotbonds) based Drug Clustering | (6) Topological Polar Surface Area (polararea) based Drug Clustering | |
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| "RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five | ||
| Co-Targets | Top | |||||
|---|---|---|---|---|---|---|
| Co-Targets | ||||||
| Target Poor or Non Binders | Top | |||||
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| Target Poor or Non Binders | ||||||
| Target Regulators | Top | |||||
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| Target-interacting Proteins | ||||||
| Target Profiles in Patients | Top | |||||
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| Target Expression Profile (TEP) | ||||||
| Target Affiliated Biological Pathways | Top | |||||
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| KEGG Pathway | [+] 4 KEGG Pathways | + | ||||
| 1 | PPAR signaling pathway | |||||
| 2 | Wnt signaling pathway | |||||
| 3 | Pathways in cancer | |||||
| 4 | Acute myeloid leukemia | |||||
| NetPath Pathway | [+] 1 NetPath Pathways | + | ||||
| 1 | IL2 Signaling Pathway | |||||
| Panther Pathway | [+] 1 Panther Pathways | + | ||||
| 1 | Wnt signaling pathway | |||||
| PID Pathway | [+] 2 PID Pathways | + | ||||
| 1 | Presenilin action in Notch and Wnt signaling | |||||
| 2 | RXR and RAR heterodimerization with other nuclear receptor | |||||
| Reactome | [+] 3 Reactome Pathways | + | ||||
| 1 | Import of palmitoyl-CoA into the mitochondrial matrix | |||||
| 2 | Regulation of pyruvate dehydrogenase (PDH) complex | |||||
| 3 | Nuclear Receptor transcription pathway | |||||
| WikiPathways | [+] 8 WikiPathways | + | ||||
| 1 | Wnt Signaling Pathway and Pluripotency | |||||
| 2 | Nuclear Receptors in Lipid Metabolism and Toxicity | |||||
| 3 | NRF2 pathway | |||||
| 4 | Nuclear Receptors Meta-Pathway | |||||
| 5 | Vitamin D Receptor Pathway | |||||
| 6 | Ectoderm Differentiation | |||||
| 7 | Adipogenesis | |||||
| 8 | Nuclear Receptors | |||||
| Target-Related Models and Studies | Top | |||||
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| Target Validation | ||||||
| References | Top | |||||
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| REF 1 | Lipid effects of peroxisome proliferator-activated receptor- agonist GW501516 in subjects with low high-density lipoprotein cholesterol: characteristics of metabolic syndrome.Arterioscler Thromb Vasc Biol.2012 Sep;32(9):2289-94. | |||||
| REF 2 | ClinicalTrials.gov (NCT02704403) Phase 3 Study to Evaluate the Efficacy and Safety of Elafibranor Versus Placebo in Patients With Nonalcoholic Steatohepatitis (NASH) (RESOLVE-IT). U.S. National Institutes of Health. | |||||
| REF 3 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800024671) | |||||
| REF 4 | ClinicalTrials.gov (NCT02560753) Feasibility Study in Subjects With Mild to Moderate Alzheimer's Disease. | |||||
| REF 5 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800028321) | |||||
| REF 6 | Kalypsys nearing completion of phase Ia study of KD3010 for metabolic disorders. Kalypsys. 2007. | |||||
| REF 7 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800029833) | |||||
| REF 8 | URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 2687). | |||||
| REF 9 | ClinicalTrials.gov (NCT00841217) Regulation of Lipoprotein Transport in Metabolic Syndrome. U.S. National Institutes of Health. | |||||
| REF 10 | Emerging drugs for non-alcoholic fatty liver disease. Expert Opin Emerg Drugs. 2008 Mar;13(1):145-58. | |||||
| REF 11 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800022483) | |||||
| REF 12 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800018093) | |||||
| REF 13 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800026847) | |||||
| REF 14 | Dual peroxisome proliferator-activated receptor / agonist GFT505 improves hepatic and peripheral insulin sensitivity in abdominally obese subjects.Diabetes Care.2013 Oct;36(10):2923-30. | |||||
| REF 15 | ClinicalTrials.gov (NCT00701883) Safety and Benefit of MBX-8025 With and Without Commonly Used Statins in Moderately Overweight Patients With High Cholesterol. U. S. National Institute of Health. 2008. | |||||
| REF 16 | Phrma report (2013 Alzheimers disease) | |||||
| REF 17 | Fibrates, glitazones, and peroxisome proliferator-activated receptors. Arterioscler Thromb Vasc Biol. 2010 May; 30(5): 894-899. | |||||
| REF 18 | Addressing Unmet Medical Needs in Type 2 Diabetes: A Narrative Review of Drugs under Development. Curr Diabetes Rev. 2015 March; 11(1): 17-31. | |||||
| REF 19 | PPAR ligands and their therapeutic applications: a patent review (2008 - 2014).Expert Opin Ther Pat. 2015 Feb;25(2):175-91. | |||||
| REF 20 | Scaffold-based discovery of indeglitazar, a PPAR pan-active anti-diabetic agent. Proc Natl Acad Sci U S A. 2009 Jan 6;106(1):262-7. | |||||
| REF 21 | Docking and molecular dynamics simulations of peroxisome proliferator activated receptors interacting with pan agonist sodelglitazar. Protein Pept Lett. 2011 Oct;18(10):1021-7. | |||||
| REF 22 | Peroxisome Proliferators-Activated Receptor (PPAR) Modulators and Metabolic Disorders. PPAR Res. 2008; 2008: 679137. | |||||
| REF 23 | DrugBank 3.0: a comprehensive resource for 'omics' research on drugs. Nucleic Acids Res. 2011 Jan;39(Database issue):D1035-41. | |||||
| REF 24 | CN patent application no. 102459215, 3-(4-aminophenyl)-2-furancarboxylic acid derivative and pharmaceutically acceptable salt thereof. | |||||
| REF 25 | Identification and characterization of 4-chloro-N-(2-{[5-trifluoromethyl)-2-pyridyl]sulfonyl}ethyl)benzamide (GSK3787), a selective and irreversibl... J Med Chem. 2010 Feb 25;53(4):1857-61. | |||||
| REF 26 | Novel selective small molecule agonists for peroxisome proliferator-activated receptor delta (PPARdelta)--synthesis and biological activity. Bioorg Med Chem Lett. 2003 May 5;13(9):1517-21. | |||||
| REF 27 | Identification of peroxisome proliferator-activated receptor ligands from a biased chemical library. Chem Biol. 1997 Dec;4(12):909-18. | |||||
| REF 28 | Novel peroxisome proliferator-activated receptor (PPAR) gamma and PPARdelta ligands produce distinct biological effects. J Biol Chem. 1999 Mar 5;274(10):6718-25. | |||||
| REF 29 | Phenylacetic acid derivatives as hPPAR agonists. Bioorg Med Chem Lett. 2003 Apr 7;13(7):1277-80. | |||||
| REF 30 | URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 594). | |||||
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