Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTZMAO3)

• DTT Name: Peroxisome proliferator-activated receptor gamma (PPAR-gamma)
• Synonyms: PPAR-gamma; Nuclear receptor subfamily 1 group C member 3; NR1C3
• Gene Name: PPARG
• DTT Type: Successful target; [1]
• BioChemical Class: Nuclear hormone receptor
• UniProt ID: PPARG_HUMAN
• TTD ID: T58921
• Sequence:
  MGETLGDSPIDPESDSFTDTLSANISQEMTMVDTEMPFWPTNFGISSVDLSVMEDHSHSF
  DIKPFTTVDFSSISTPHYEDIPFTRTDPVVADYKYDLKLQEYQSAIKVEPASPPYYSEKT
  QLYNKPHEEPSNSLMAIECRVCGDKASGFHYGVHACEGCKGFFRRTIRLKLIYDRCDLNC
  RIHKKSRNKCQYCRFQKCLAVGMSHNAIRFGRMPQAEKEKLLAEISSDIDQLNPESADLR
  ALAKHLYDSYIKSFPLTKAKARAILTGKTTDKSPFVIYDMNSLMMGEDKIKFKHITPLQE
  QSKEVAIRIFQGCQFRSVEAVQEITEYAKSIPGFVNLDLNDQVTLLKYGVHEIIYTMLAS
  LMNKDGVLISEGQGFMTREFLKSLRKPFGDFMEPKFEFAVKFNALELDDSDLAIFIAVII
  LSGDRPGLLNVKPIEDIQDNLLQALELQLKLNHPESSQLFAKLLQKMTDLRQIVTEHVQL
  LQVIKKTETDMSLHPLLQEIYKDLY
• Function: Nuclear receptor that binds peroxisome proliferators such as hypolipidemic drugs and fatty acids. Once activated by a ligand, the nuclear receptor binds to DNA specific PPAR response elements (PPRE) and modulates the transcription of its target genes, such as acyl-CoA oxidase. It therefore controls the peroxisomal beta-oxidation pathway of fatty acids. Key regulator of adipocyte differentiation and glucose homeostasis. ARF6 acts as a key regulator of the tissue-specific adipocyte P2 (aP2) enhancer. Acts as a critical regulator of gut homeostasis by suppressing NF-kappa-B-mediated proinflammatory responses. Plays a role in the regulation of cardiovascular circadian rhythms by regulating the transcription of ARNTL/BMAL1 in the blood vessels (By similarity).
• KEGG Pathway:
  PPAR signaling pathway (hsa03320)
  AMPK signaling pathway (hsa04152)
  Osteoclast differentiation (hsa04380)
  Huntington's disease (hsa05016)
  Pathways in cancer (hsa05200)
  Transcriptional misregulation in cancer (hsa05202)
  Thyroid cancer (hsa05216)
• Reactome Pathway:
  Transcriptional regulation of white adipocyte differentiation (R-HSA-381340)
  Nuclear Receptor transcription pathway (R-HSA-383280)
  PPARA activates gene expression (R-HSA-1989781)

Molecular Interaction Atlas (MIA) of This DTT

6 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Lobeglitazone	DMHY3IP	Type-2 diabetes	5A11	Approved	[2]
Pioglitazone	DMKJ485	Amyotrophic lateral sclerosis	8B60.0	Approved	[1]
Rosiglitazone XR	DMT45MU	Type-2 diabetes	5A11	Approved	[3]
Thiazolidinedione	DMC1NBW	Alzheimer disease	8A20	Approved	[1]
Troglitazone	DM3VFPD	Diabetic complication	5A2Y	Approved	[4]
Glitazone	DMDN4A1	N. A.	N. A.	Phase 4	[5]

25 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Balaglitazone	DMXBHR6	Type-1 diabetes	5A10	Phase 3	[6]
CS-038	DM67P0F	Type-2 diabetes	5A11	Phase 3	[7]
FARGLITAZAR	DMOKT7Y	Type-1 diabetes	5A10	Phase 3	[8]
Imiglitazar	DM7BCWT	Type-2 diabetes	5A11	Phase 3	[9]
Leriglitazone	DMQFD42	Cerebral X-linked adrenoleukodystrophy	5C57.1	Phase 3	[10]
MURAGLITAZAR	DMG3NFZ	N. A.	N. A.	Phase 3	[11]
Ragaglitazar	DMFSHEM	Type-1 diabetes	5A10	Phase 3	[12]
Rivoglitazone	DMBY31K	Ocular inflammation	9C61.24	Phase 3	[13]
TESAGLITAZAR	DMGRBN5	Type-1 diabetes	5A10	Phase 3	[14]
ZYH-1	DMMBJYC	Lipid metabolism disorder	5C52.Z	Phase 3	[15]
MBX-102	DMONYS9	Gout	FA25	Phase 2/3	[16]
CHS-131	DMMRKPF	Multiple sclerosis	8A40	Phase 2	[17]
FK-614	DMY61TJ	Type-2 diabetes	5A11	Phase 2	[18]
GED-0507-34-Levo	DMMQY0O	Inflammatory bowel disease	DD72	Phase 2	[19]
MBX-2044	DMQMTO1	Type-2 diabetes	5A11	Phase 2	[16]
Naveglitazar	DMD0E8U	Diabetic complication	5A2Y	Phase 2	[20]
Netoglitazone	DM8H7OA	Non-alcoholic fatty liver disease	DB92	Phase 2	[21]
OMS405	DMWC36Y	Nicotine dependence	6C4A.2	Phase 2	[22]
ONO-5129	DMFX3P1	Diabetic complication	5A2Y	Phase 2	[23]
T3D-959	DMR3245	Alzheimer disease	8A20	Phase 2	[24]
CLX-0921	DMJQG25	Type-2 diabetes	5A11	Phase 1	[25]
DSP-8658	DM2PYE0	Alzheimer disease	8A20	Phase 1	[26]
Englitazone sodium	DMKPBVX	Type-2 diabetes	5A11	Phase 1	[27]
GW-409544	DMOE5SZ	Hyperlipidaemia	5C80	Phase 1	[28]
Oxeglitazar	DMN4LMT	Gout	FA25	Phase 1	[29]

24 Patented Agent(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
1-(biphenyl-4-yl-methyl)-1H-imidazole derivative 1	DMGYZQ2	N. A.	N. A.	Patented	[30]
3-phenyl acrylic acid derivative 1	DMXMV6N	N. A.	N. A.	Patented	[30]
A-substituted phenylpropionic acid derivative 1	DMGM72Q	N. A.	N. A.	Patented	[30]
A-substituted phenylpropionic acid derivative 2	DMH5FEO	N. A.	N. A.	Patented	[30]
Biaromatic compound 1	DMJG1ZS	N. A.	N. A.	Patented	[30]
Cannabinoid quinone derivative 1	DM81SYN	N. A.	N. A.	Patented	[30]
Crystalline anhydrous toluene derivative 1	DM76Q10	N. A.	N. A.	Patented	[30]
Flavonoid derivative 8	DM4O9T3	N. A.	N. A.	Patented	[30]
Fused aromatic compound 1	DM4EUFL	N. A.	N. A.	Patented	[30]
Fused ring compound 1	DMPHL3J	N. A.	N. A.	Patented	[30]
MRL20	DMNGQ3I	Discovery agent	N.A.	Patented	[30]
MRL24	DM8NS7U	Discovery agent	N.A.	Patented	[30]
Phenylpropionic acid derivative 1	DMTEJRB	N. A.	N. A.	Patented	[30]
Phenylpyridine derivative 3	DMDT5JI	N. A.	N. A.	Patented	[30]
PMID25416646-Compound-Figure2-J	DMJETVH	N. A.	N. A.	Patented	[30]
PMID25416646-Compound-Figure2-K	DMNTAYK	N. A.	N. A.	Patented	[30]
PMID25416646-Compound-Figure2-N	DMLDPGY	N. A.	N. A.	Patented	[30]
PMID25416646-Compound-Figure5-A	DM9OHAN	N. A.	N. A.	Patented	[30]
PMID25416646-Compound-Figure5-C	DM17FKL	N. A.	N. A.	Patented	[30]
PMID25416646-Compound-Figure5-E	DMYO7VH	N. A.	N. A.	Patented	[30]
PMID25416646-Compound-Figure5-H	DMCJTU1	N. A.	N. A.	Patented	[30]
Spirolaxine derivative 1	DMK5G7D	N. A.	N. A.	Patented	[30]
Sulfonamide derivative 18	DMHTJ7N	N. A.	N. A.	Patented	[30]
Thiazolidine dione crystalline derivative 1	DMLBA4D	N. A.	N. A.	Patented	[30]

18 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
AVE-0847	DMRYK1C	Hyperlipidaemia	5C80	Discontinued in Phase 2	[31]
GSK-677954	DM5WRJX	Non-alcoholic fatty liver disease	DB92	Discontinued in Phase 2	[32]
Indeglitazar	DMS56UD	Type-2 diabetes	5A11	Discontinued in Phase 2	[33]
KRP-297	DM9VHZC	Type-2 diabetes	5A11	Discontinued in Phase 2	[34]
Reglixane	DMIN73Y	Diabetic complication	5A2Y	Discontinued in Phase 2	[23]
Sodelglitazar	DMJ816F	Hyperlipidaemia	5C80	Discontinued in Phase 2	[35]
YM-440	DM7OHR6	Type-1 diabetes	5A10	Discontinued in Phase 2	[36]
DS-6930	DMDAO8E	Diabetic complication	5A2Y	Discontinued in Phase 1	[37]
E-3030	DMJWR1I	Hyperlipidaemia	5C80	Discontinued in Phase 1	[38]
LY-929	DMVYG5X	Lipid metabolism disorder	5C52.Z	Discontinued in Phase 1	[39]
AD-5075	DM1SLJ9	Type-2 diabetes	5A11	Terminated	[41]
AKP-320	DMMTZXV	Type-2 diabetes	5A11	Terminated	[42]
BVT-142	DMIYPLU	Type-2 diabetes	5A11	Terminated	[43]
CS-204	DM1E7H3	Metabolic disorder	5C50-5D2Z	Terminated	[44]
DARGLITAZONE	DM6IGRL	Diabetic complication	5A2Y	Terminated	[45]
Edaglitazone	DMIC460	Type-2 diabetes	5A11	Terminated	[46]
SB-219994	DMCZDE9	Diabetic complication	5A2Y	Terminated	[47]
Sipoglitazar	DM5SBUJ	Diabetic complication	5A2Y	Terminated	[15]

2 Preclinical Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Ciglitazone	DMAPO0T	Pulmonary fibrosis	CB03.4	Preclinical	[40]
MC-3002	DM7UGY9	Metabolic disorder	5C50-5D2Z	Preclinical	[23]

12 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
(2S)-2-(4-chlorophenoxy)-3-phenylpropanoic acid	DMNKEUG	Discovery agent	N.A.	Investigative	[48]
(2S)-2-(4-ethylphenoxy)-3-phenylpropanoic acid	DMYBXHF	Discovery agent	N.A.	Investigative	[48]
(2S)-2-(biphenyl-4-yloxy)-3-phenylpropanoic acid	DM73TPQ	Discovery agent	N.A.	Investigative	[48]
(9Z,11E,13S)-13-hydroxyoctadeca-9,11-dienoic acid	DM12GHQ	Discovery agent	N.A.	Investigative	[48]
15-deoxy-Delta(12, 14)-prostaglandin J(2)	DM8VUX3	Discovery agent	N.A.	Investigative	[4]
2-chloro-5-nitro-N-phenylbenzamide	DMUGQIV	Discovery agent	N.A.	Investigative	[48]
3-(5-methoxy-1H-indol-3-yl)propanoic acid	DMXLVG6	Discovery agent	N.A.	Investigative	[48]
9-hydroxyoctadecadienoic acid	DM0FWNJ	Discovery agent	N.A.	Investigative	[48]
DB-900	DMGRUN1	Type-2 diabetes	5A11	Investigative	[49]
GW-2331	DMM8V9E	Discovery agent	N.A.	Investigative	[50]
GW7845	DMEK2I4	Discovery agent	N.A.	Investigative	[51]
ZY H2	DMN9UCI	Discovery agent	N.A.	Investigative	[52]

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	9.17E-01	0.04	0.09
Endometriosis	GA10	Endometrium tissue	2.42E-02	0.17	0.19
Prostate cancer	2C82	Prostate	1.82E-02	-0.49	-0.79
Lung cancer	2C82	Lung tissue	2.56E-83	-1.79	-2.42
Alzheimer's disease	8A00.0	Entorhinal cortex	2.41E-01	-0.06	-0.25
Non-alcoholic fatty liver disease	DD91.0	Liver tissue	2.44E-02	0.64	1.33

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