Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTJ584C)

• DTT Name: Peroxisome proliferator-activated receptor alpha (PPARA)
• Synonyms: Peroxisome proliferater-activated receptor alpha; PPARalpha; PPAR-alpha; PPAR; Nuclear receptor subfamily 1 group C member 1; NR1C1
• Gene Name: PPARA
• DTT Type: Successful target; [1]
• Related Disease:
  Hyper-lipoproteinaemia [ICD-11: 5C80]
  Hyperlipidemia [ICD-11: 5C80]
  Type 2 diabetes mellitus [ICD-11: 5A11]
• BioChemical Class: Nuclear hormone receptor
• UniProt ID: PPARA_HUMAN
• TTD ID: T86591
• Sequence:
  MVDTESPLCPLSPLEAGDLESPLSEEFLQEMGNIQEISQSIGEDSSGSFGFTEYQYLGSC
  PGSDGSVITDTLSPASSPSSVTYPVVPGSVDESPSGALNIECRICGDKASGYHYGVHACE
  GCKGFFRRTIRLKLVYDKCDRSCKIQKKNRNKCQYCRFHKCLSVGMSHNAIRFGRMPRSE
  KAKLKAEILTCEHDIEDSETADLKSLAKRIYEAYLKNFNMNKVKARVILSGKASNNPPFV
  IHDMETLCMAEKTLVAKLVANGIQNKEAEVRIFHCCQCTSVETVTELTEFAKAIPGFANL
  DLNDQVTLLKYGVYEAIFAMLSSVMNKDGMLVAYGNGFITREFLKSLRKPFCDIMEPKFD
  FAMKFNALELDDSDISLFVAAIICCGDRPGLLNVGHIEKMQEGIVHVLRLHLQSNHPDDI
  FLFPKLLQKMADLRQLVTEHAQLVQIIKKTESDAALHPLLQEIYRDMY
• Function: Key regulator of lipid metabolism. Activated by the endogenous ligand 1-palmitoyl-2-oleoyl-sn-glycerol-3-phosphocholine (16:0/18:1-GPC). Activated by oleylethanolamide, a naturally occurring lipid that regulates satiety. Receptor for peroxisome proliferators such as hypolipidemic drugs and fatty acids. Regulates the peroxisomal beta-oxidation pathway of fatty acids. Functions as transcription activator for the ACOX1 and P450 genes. Transactivation activity requires heterodimerization with RXRA and is antagonized by NR2C2. May be required for the propagation of clock information to metabolic pathways regulated by PER2. Ligand-activated transcription factor.
• KEGG Pathway:
  PPAR signaling pathway (hsa03320)
  cAMP signaling pathway (hsa04024)
  Adipocytokine signaling pathway (hsa04920)
  Glucagon signaling pathway (hsa04922)
  Non-alcoholic fatty liver disease (NAFLD) (hsa04932)
  Hepatitis C (hsa05160)
• Reactome Pathway:
  BMAL1 (R-HSA-1368108)
  PPARA activates gene expression (R-HSA-1989781)
  YAP1- and WWTR1 (TAZ)-stimulated gene expression (R-HSA-2032785)
  Transcriptional activation of mitochondrial biogenesis (R-HSA-2151201)
  Activation of gene expression by SREBF (SREBP) (R-HSA-2426168)
  Transcriptional regulation of white adipocyte differentiation (R-HSA-381340)
  Nuclear Receptor transcription pathway (R-HSA-383280)
  Regulation of lipid metabolism by Peroxisome proliferator-activated receptor alpha (PPARalpha) (R-HSA-400206)
  Circadian Clock (R-HSA-400253)
  RORA activates gene expression (R-HSA-1368082)

Molecular Interaction Atlas (MIA) of This DTT

5 Approved Drug(s) Targeting This DTT

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

17 Clinical Trial Drug(s) Targeting This DTT

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) Targeting This DTT

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) Targeting This DTT

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) Targeting This DTT

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) Targeting This DTT

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	[1], [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]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Type 2 diabetes	5A11	Liver tissue	1.74E-01	-0.17	-0.3
Non-alcoholic fatty liver disease	DD91.0	Liver tissue	2.89E-01	-0.25	-0.67
Rheumatoid arthritis	FA20	Synovial tissue	1.12E-01	0.35	0.96
Coronary artery disease	BA80-BA8Z	Peripheral blood	1.54E-03	-0.29	-1.6

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