Details of the Drug-Related molecule(s) Interaction Atlas

General Information of DTT (ID: TTJ584C)

• DTT Name: Peroxisome proliferator-activated receptor alpha (PPARA) DTT Info
• UniProt ID: PPARA_HUMAN
• Gene Name: PPARA

Molecule-Related Drug & Molecule List

5 Approved Drug(s) Transported by This DTP

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Bezafibrate	DMZDCS0	Hyperlipidaemia	5C80	Approved	[1]
Ciprofibrate	DMGC5DB	Hyperlipoproteinemia	5C80	Approved	[2]
Fenofibrate	DMFKXDY	High cholesterol level	5C80.0	Approved	[2]
Lobeglitazone	DMHY3IP	Type-2 diabetes	5A11	Approved	[3]
Pemafibrate	DMD1VZL	Hyperlipidemia	5C80.Z	Approved	[4]

17 Clinical Trial Drug(s) Transported by This DTP

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
CS-038	DM67P0F	Type-2 diabetes	5A11	Phase 3	[5], [6]
GFT-505	DM7ZOAE	Non-alcoholic steatohepatitis	DB92.1	Phase 3	[7]
Imiglitazar	DM7BCWT	Type-2 diabetes	5A11	Phase 3	[8], [9]
Muraglitazar	DMG3NFZ	N. A.	N. A.	Phase 3	[10]
Ragaglitazar	DMFSHEM	Type-1 diabetes	5A10	Phase 3	[11]
TESAGLITAZAR	DMGRBN5	Type-1 diabetes	5A10	Phase 3	[12]
ZYH-1	DMMBJYC	Lipid metabolism disorder	5C52.Z	Phase 3	[13]
GFT14	DMD3RU8	Hyperlipidaemia	5C80	Phase 2	[14]
LY-518674	DMBM2I9	Diabetic complication	5A2Y	Phase 2	[15]
Naveglitazar	DMD0E8U	Diabetic complication	5A2Y	Phase 2	[16]
ONO-5129	DMFX3P1	Diabetic complication	5A2Y	Phase 2	[17]
ZYH7	DMG7YI9	Dyslipidemia	5C80-5C81	Phase 2	[18]
AVE0897	DM56VG2	Type-2 diabetes	5A11	Phase 1	[19]
CDT-fenofibrate	DMKUXB5	Hyperlipidaemia	5C80	Phase 1	[20]
GW-409544	DMOE5SZ	Hyperlipidaemia	5C80	Phase 1	[21]
Oxeglitazar	DMN4LMT	Gout	FA25	Phase 1	[22]
TPST-1120	DMG4U32	Solid tumour/cancer	2A00-2F9Z	Phase 1	[23]

3 Patented Agent(s) Transported by This DTP

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Flavonoid derivative 8	DM4O9T3	N. A.	N. A.	Patented	[24]
PMID25416646-Compound-Figure5-A	DM9OHAN	N. A.	N. A.	Patented	[24]
PMID25416646-Compound-Figure5-H	DMCJTU1	N. A.	N. A.	Patented	[24]

22 Discontinued Drug(s) Transported by This DTP

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Aleglitazar	DMTG18I	Type-2 diabetes	5A11	Discontinued in Phase 3	[25]
AVE-0847	DMRYK1C	Hyperlipidaemia	5C80	Discontinued in Phase 2	[26]
AVE-8134	DMCX6MD	Heart failure	BD10-BD13	Discontinued in Phase 2	[27]
BM-17.0744	DM7ZI8A	Type-1 diabetes	5A10	Discontinued in Phase 2	[28], [29]
GSK-677954	DM5WRJX	Non-alcoholic fatty liver disease	DB92	Discontinued in Phase 2	[30]
Indeglitazar	DMS56UD	Type-2 diabetes	5A11	Discontinued in Phase 2	[31]
KRP-101	DMBU9O4	Hyperlipidaemia	5C80	Discontinued in Phase 2	[32], [33]
KRP-297	DM9VHZC	Type-2 diabetes	5A11	Discontinued in Phase 2	[34]
NS-220	DMQ82T5	Hyperlipidaemia	5C80	Discontinued in Phase 2	[35], [29]
Reglixane	DMIN73Y	Diabetic complication	5A2Y	Discontinued in Phase 2	[17]
Sodelglitazar	DMJ816F	Hyperlipidaemia	5C80	Discontinued in Phase 2	[36]
AR-H049020	DMHZN42	Type-1 diabetes	5A10	Discontinued in Phase 1	[37]
DRF 10945	DMOPM7L	Hyperlipidaemia	5C80	Discontinued in Phase 1	[38]
E-3030	DMJWR1I	Hyperlipidaemia	5C80	Discontinued in Phase 1	[39]
LG-101280	DM0PXGU	Arteriosclerosis	BD40	Discontinued in Phase 1	[40]
LY-929	DMVYG5X	Lipid metabolism disorder	5C52.Z	Discontinued in Phase 1	[41]
MP-136	DMK91WR	Lipid metabolism disorder	5C52.Z	Discontinued in Phase 1	[42]
BVT-142	DMIYPLU	Type-2 diabetes	5A11	Terminated	[46], [47]
CS-204	DM1E7H3	Metabolic disorder	5C50-5D2Z	Terminated	[48]
CS-207	DMFJ4VT	Cardiovascular disease	BA00-BE2Z	Terminated	[49]
KRP-105	DMVZSAM	Lipid metabolism disorder	5C52.Z	Terminated	[50]
Sipoglitazar	DM5SBUJ	Diabetic complication	5A2Y	Terminated	[13]

4 Preclinical Drug(s) Transported by This DTP

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
MC-3001	DMLK2D0	Lipid metabolism disorder	5C52.Z	Preclinical	[43]
MC-3002	DM7UGY9	Metabolic disorder	5C50-5D2Z	Preclinical	[17]
PIRINIXIC ACID	DM82Y75	Pulmonary fibrosis	CB03.4	Preclinical	[44]
Romazarit	DMZOUX4	Rheumatoid arthritis	FA20	Preclinical	[45]

25 Investigative Drug(s) Transported by This DTP

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
(9Z,12E)-12-nitrooctadeca-9,12-dienoic acid	DM2REIN	Discovery agent	N.A.	Investigative	[51]
(E)-12-Nitrooctadec-12-enoic Acid	DMBQTZL	Discovery agent	N.A.	Investigative	[51]
(E)-13-Nitrooctadec-12-enoic Acid	DMF74GJ	Discovery agent	N.A.	Investigative	[51]
(E)-4-(3,5-dimethoxystyryl)phenol	DMYXI2V	Discovery agent	N.A.	Investigative	[42]
8S-HETE	DMT9SAC	Discovery agent	N.A.	Investigative	[52]
AD-5061	DM5WV13	Discovery agent	N.A.	Investigative	[8]
BMS-687453	DMYAPG5	Discovery agent	N.A.	Investigative	[53]
CP-775146	DMANV7R	Discovery agent	N.A.	Investigative	[54]
DB-900	DMGRUN1	Type-2 diabetes	5A11	Investigative	[55]
Deoxy-Bigchap	DMYAJCG	Discovery agent	N.A.	Investigative	[56]
DRF 2519	DMTFQG3	Discovery agent	N.A.	Investigative	[57]
eicosatetranoic acid	DMAKP20	Discovery agent	N.A.	Investigative	[58]
Fibrates	DMFNTMY	Dyslipidemia	5C80-5C81	Investigative	[59]
GSK-9578	DMW9AN1	Discovery agent	N.A.	Investigative	[2], [60]
GW-2331	DMM8V9E	Discovery agent	N.A.	Investigative	[61]
GW7647	DM9RD0C	Discovery agent	N.A.	Investigative	[62]
L-165461	DMKBSGN	Discovery agent	N.A.	Investigative	[63]
L-796449	DMWTGQM	Discovery agent	N.A.	Investigative	[63]
LL-6531	DM6RCES	Diabetic complication	5A2Y	Investigative	[42]
LY-465608	DMK64AZ	Discovery agent	N.A.	Investigative	[64]
N-oleoylethanolamide	DMJQ4L7	Discovery agent	N.A.	Investigative	[65]
pristanic acid	DMTJZQK	Discovery agent	N.A.	Investigative	[66]
reglitazar	DMQ3ER0	Discovery agent	N.A.	Investigative	[67]
TZD18	DMVCHOX	Discovery agent	N.A.	Investigative	[68]
ZY H2	DMN9UCI	Discovery agent	N.A.	Investigative	[69]

References

• [1] Bezafibrate at clinically relevant doses decreases serum/liver triglycerides via down-regulation of sterol regulatory element-binding protein-1c in... Mol Pharmacol. 2009 Apr;75(4):782-92.
• [2] Peroxisome proliferator-activated receptor alpha activators improve insulin sensitivity and reduce adiposity. J Biol Chem. 2000 Jun 2;275(22):16638-42.
• [3] Tolerability and pharmacokinetics of lobeglitazone, a novel peroxisome proliferator-activated receptor-gamma agonist, after a single oral administration in healthy female subjects. Clin Drug Investig. 2014 Jul;34(7):467-74.
• [4] Pemafibrate: First Global Approval. Drugs. 2017 Oct;77(16):1805-1810.
• [5] Determination of chiglitazar, a dual alpha/gamma peroxisome proliferator-activated receptor (PPAR) agonist, in human plasma by liquid chromatograph... Pharmazie. 2007 Nov;62(11):825-9.
• [6] The PPARalpha/gamma dual agonist chiglitazar improves insulin resistance and dyslipidemia in MSG obese rats.Br J Pharmacol.2006 Jul;148(5):610-8.
• [7] 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.
• [8] A novel oxyiminoalkanoic acid derivative, TAK-559, activates human peroxisome proliferator-activated receptor subtypes. Eur J Pharmacol. 2004 Jul 8;495(1):17-26.
• [9] A potent activator of PPARalpha and gamma reduces the vascular cell recruitment and inhibits the intimal thickning in hypercholesterolemic rabbits. Atherosclerosis. 2005 Jan;178(1):1-7.
• [10] Muraglitazar, a dual (alpha/gamma) PPAR activator: a randomized, double-blind, placebo-controlled, 24-week monotherapy trial in adult patients with... Clin Ther. 2005 Aug;27(8):1181-95.
• [11] Ragaglitazar: the pharmacokinetics, pharmacodynamics, and tolerability of a novel dual PPAR alpha and gamma agonist in healthy subjects and patients with type 2 diabetes. J Clin Pharmacol. 2003 Nov;43(11):1244-56.
• [12] Tesaglitazar, a dual PPAR-/ agonist, hamster carcinogenicity, investigative animal and clinical studies.Toxicol Pathol.2012;40(1):18-32.
• [13] Pharmacokinetics, safety, and tolerability of saroglitazar (ZYH1), a predominantly PPARalpha agonist with moderate PPARgamma agonist activity in healthy human subjects. Clin Drug Investig. 2013 Nov;33(11):809-16.
• [14] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800024296)
• [15] Potent and selective PPAR-alpha agonist LY518674 upregulates both ApoA-I production and catabolism in human subjects with the metabolic syndrome. Arterioscler Thromb Vasc Biol. 2009 Jan;29(1):140-6.
• [16] The disposition and metabolism of naveglitazar, a peroxisome proliferator-activated receptor alpha-gamma dual, gamma-dominant agonist in mice, rats... Drug Metab Dispos. 2007 Jan;35(1):51-61.
• [17] Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.
• [18] Clinical pipeline report, company report or official report of Zydus Cadila.
• [19] Pharma & Vaccines. Product Development Pipeline. April 29 2009.
• [20] Mechanism of action of fibrates on lipid and lipoprotein metabolism. Circulation. 1998 Nov 10;98(19):2088-93.
• [21] Design novel dual agonists for treating type-2 diabetes by targeting peroxisome proliferator-activated receptors with core hopping approach. PLoS One. 2012;7(6):e38546.
• [22] Therapeutic potential of aleglitazar, a new dual PPAR-alpha/gamma agonist: implications for cardiovascular disease in patients with diabetes mellitus. Am J Cardiovasc Drugs. 2010;10(4):209-16.
• [23] Clinical pipeline report, company report or official report of Tempest Therapeutics.
• [24] PPAR ligands and their therapeutic applications: a patent review (2008 - 2014).Expert Opin Ther Pat. 2015 Feb;25(2):175-91.
• [25] Clinical pipeline report, company report or official report of Roche (2009).
• [26] DOI: 10.1038/scibx.2012.669
• [27] The peroxisome proliferator-activated receptor-alpha (PPAR-alpha) agonist, AVE8134, attenuates the progression of heart failure and increases survival in rats. Acta Pharmacol Sin. 2009 Jul;30(7):935-46.
• [28] Cardiac function and metabolism in Type 2 diabetic mice after treatment with BM 17.0744, a novel PPAR-alpha activator. Am J Physiol Heart Circ Physiol. 2002 Sep;283(3):H949-57.
• [29] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [30] Emerging drugs for non-alcoholic fatty liver disease. Expert Opin Emerg Drugs. 2008 Mar;13(1):145-58.
• [31] 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.
• [32] Identification of a functional peroxisome proliferator-activated receptor (PPAR) response element (PPRE) in the human apolipoprotein A-IV gene. Biochem Pharmacol. 2009 Sep 1;78(5):523-30.
• [33] A novel PPARalpha agonist ameliorates insulin resistance in dogs fed a high-fat diet. Am J Physiol Endocrinol Metab. 2008 May;294(5):E833-40.
• [34] KRP-297, MCC-555. Nihon Rinsho. 2001 Nov;59(11):2200-6.
• [35] Modulation of PPAR receptor subtype selectivity of the ligands: aliphatic chain vs aromatic ring as a spacer between pharmacophore and the lipophilic moiety. Bioorg Med Chem Lett. 2008 Dec 15;18(24):6471-5.
• [36] Docking and molecular dynamics simulations of peroxisome proliferator activated receptors interacting with pan agonist sodelglitazar. Protein Pept Lett. 2011 Oct;18(10):1021-7.
• [37] CN patent application no. 100577175, Combination therapy comprising glucose reabsorption inhibitors and PPAR modulators.
• [38] Peroxisome proliferator-activated receptors, metabolic syndrome and cardiovascular disease. Future Cardiol. 2010 September; 6(5): 657-691.
• [39] Antidiabetic and hypolipidemic effects of a novel dual peroxisome proliferator-activated receptor (PPAR) alpha/gamma agonist, E3030, in db/db mice and beagle dogs.J Pharmacol Sci.2008 Sep;108(1):40-8.
• [40] A peroxisome proliferator-activated receptor alpha/gamma dual agonist with a unique in vitro profile and potent glucose and lipid effects in rodent... Mol Endocrinol. 2005 Jun;19(6):1593-605.
• [41] CN patent application no. 1882326, Ppar agonists for the treatment of hcv infection.
• [42] 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: 593).
• [43] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800021175)
• [44] O-arylmandelic acids as highly selective human PPAR alpha/gamma agonists. Bioorg Med Chem Lett. 2003 Oct 6;13(19):3185-90.
• [45] Fibrates as therapy for osteoarthritis and rheumatoid arthritis A systematic review. Ther Adv Musculoskelet Dis. 2013 February; 5(1): 33-44.
• [46] A new class of peroxisome proliferator-activated receptor agonists with a novel binding epitope shows antidiabetic effects. J Biol Chem. 2004 Sep 24;279(39):41124-30.
• [47] US patent application no. 7,816,328, Substituted fused heterocyclic c-glycosides.
• [48] Peroxisome Proliferators-Activated Receptor (PPAR) Modulators and Metabolic Disorders. PPAR Res. 2008; 2008: 679137.
• [49] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800026848)
• [50] Discovery of cyclic amine-substituted benzoic acids as PPARalpha agonists. Bioorg Med Chem Lett. 2012 Jan 1;22(1):334-8.
• [51] Activation of peroxisome proliferator-activated receptor gamma (PPARgamma) by nitroalkene fatty acids: importance of nitration position and degree ... J Med Chem. 2009 Aug 13;52(15):4631-9.
• [52] Differential activation of peroxisome proliferator-activated receptors by eicosanoids. J Biol Chem. 1995 Oct 13;270(41):23975-83.
• [53] Discovery of an oxybenzylglycine based peroxisome proliferator activated receptor alpha selective agonist 2-((3-((2-(4-chlorophenyl)-5-methyloxazol... J Med Chem. 2010 Apr 8;53(7):2854-64.
• [54] Molecular characterization of novel and selective peroxisome proliferator-activated receptor alpha agonists with robust hypolipidemic activity in vivo. Mol Pharmacol. 2009 Feb;75(2):296-306.
• [55] CN patent application no. 102459215, 3-(4-aminophenyl)-2-furancarboxylic acid derivative and pharmaceutically acceptable salt thereof.
• [56] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
• [57] Antidiabetic and hypolipidemic potential of DRF 2519--a dual activator of PPAR-alpha and PPAR-gamma. Eur J Pharmacol. 2004 May 3;491(2-3):195-206.
• [58] PPAR alpha structure-function relationships derived from species-specific differences in responsiveness to hypolipidemic agents. Biol Chem. 1997 Jul;378(7):651-5.
• [59] Emerging antidyslipidemic drugs. Expert Opin Emerg Drugs. 2008 Jun;13(2):363-81.
• [60] Design and synthesis of a potent and selective triazolone-based peroxisome proliferator-activated receptor alpha agonist. J Med Chem. 2003 Nov 20;46(24):5121-4.
• [61] PPAR-alpha and -gamma but not -delta agonists inhibit airway inflammation in a murine model of asthma: in vitro evidence for an NF-kappaB-independe... Br J Pharmacol. 2003 May;139(1):163-71.
• [62] Identification of a subtype selective human PPARalpha agonist through parallel-array synthesis. Bioorg Med Chem Lett. 2001 May 7;11(9):1225-7.
• [63] Phenylacetic acid derivatives as hPPAR agonists. Bioorg Med Chem Lett. 2003 Apr 7;13(7):1277-80.
• [64] Design and synthesis of alpha-aryloxy-alpha-methylhydrocinnamic acids: a novel class of dual peroxisome proliferator-activated receptor alpha/gamma agonists. J Med Chem. 2004 May 6;47(10):2422-5.
• [65] Oleoylethanolamide, an endogenous PPAR-alpha agonist, lowers body weight and hyperlipidemia in obese rats. Neuropharmacology. 2005 Jun;48(8):1147-53.
• [66] Pristanic acid and phytanic acid: naturally occurring ligands for the nuclear receptor peroxisome proliferator-activated receptor alpha. J Lipid Res. 2000 Nov;41(11):1801-7.
• [67] Pharmacological profiles of a novel oral antidiabetic agent, JTT-501, an isoxazolidinedione derivative. Eur J Pharmacol. 1999 Jan 8;364(2-3):211-9.
• [68] A novel peroxisome proliferator-activated receptor alpha/gamma dual agonist demonstrates favorable effects on lipid homeostasis. Endocrinology. 2004 Apr;145(4):1640-8.
• [69] The ChEMBL database in 2017. Nucleic Acids Res. 2017 Jan 4;45(D1):D945-D954.