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

General Information of Drug (ID: DMNTAYK)

• Drug Name: PMID25416646-Compound-Figure2-K Drug Info
• Cross-matching ID:
  PubChem CID: 10229498
  CAS Number: CAS 315224-26-1
  TTD Drug ID: DMNTAYK

Molecule-Related Drug Atlas

Drug(s) Targeting Peroxisome proliferator-activated receptor gamma (PPAR-gamma)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Troglitazone	DM3VFPD	Diabetic complication	5A2Y	Approved	[4]
Pioglitazone	DMKJ485	Amyotrophic lateral sclerosis	8B60.0	Approved	[5]
Lobeglitazone	DMHY3IP	Type-2 diabetes	5A11	Approved	[6]
Rosiglitazone XR	DMT45MU	Type-2 diabetes	5A11	Approved	[7]
Thiazolidinedione	DMC1NBW	Alzheimer disease	8A20	Approved	[5]
Glitazone	DMDN4A1	N. A.	N. A.	Phase 4	[8]
MURAGLITAZAR	DMG3NFZ	N. A.	N. A.	Phase 3	[9]
Rivoglitazone	DMBY31K	Ocular inflammation	9C61.24	Phase 3	[10]
Balaglitazone	DMXBHR6	Type-1 diabetes	5A10	Phase 3	[11]
Ragaglitazar	DMFSHEM	Type-1 diabetes	5A10	Phase 3	[12]

Drug(s) Affected By Peroxisome proliferator-activated receptor gamma (PPARG)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Cannabidiol	DM0659E	Dravet syndrome	8A61.11	Approved	[13]
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[14]
Quercetin	DM3NC4M	Obesity	5B81	Approved	[15]
Troglitazone	DM3VFPD	Diabetic complication	5A2Y	Approved	[16]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[17]
Glucosamine	DM4ZLFD	Osteoarthritis	FA00-FA05	Approved	[18]
Isoniazid	DM5JVS3	Latent tuberculosis infection		Approved	[19]
Arsenic trioxide	DM61TA4	Acute lymphoblastic leukaemia	2A85	Approved	[20]
Aspirin	DM672AH	Acute coronary syndrome	BA41	Approved	[21]
Stavudine	DM6DEK9	Human immunodeficiency virus infection	1C62	Approved	[22]

Drug(s) Affected By Mediator of RNA polymerase II transcription subunit 1 (MED1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Fulvestrant	DM0YZC6	Breast cancer	2C60-2C65	Approved	[23]
Quercetin	DM3NC4M	Obesity	5B81	Approved	[24]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[25]
Rifampicin	DM5DSFZ	Non-insulin dependent diabetes	5A11	Approved	[26]
Leflunomide	DMR8ONJ	Arthritis	FA20	Approved	[27]
Ciclosporin	DMAZJFX	Graft-versus-host disease	4B24	Approved	[28]
Ivermectin	DMDBX5F	Intestinal strongyloidiasis due to nematode parasite	1F6B	Approved	[29]
Rosiglitazone	DMILWZR	Chronic kidney disease	GB61	Approved	[2]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[30]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[23]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Peroxisome proliferator-activated receptor gamma (PPAR-gamma)	TTZMAO3	PPARG_HUMAN	Agonist	[1]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Mediator of RNA polymerase II transcription subunit 1 (MED1)	OTOO24C4	MED1_HUMAN	Protein Interaction/Cellular Processes	[2]
Peroxisome proliferator-activated receptor gamma (PPARG)	OTHMARHO	PPARG_HUMAN	Gene/Protein Processing	[3]

References

• [1] PPAR ligands and their therapeutic applications: a patent review (2008 - 2014).Expert Opin Ther Pat. 2015 Feb;25(2):175-91.
• [2] Selective Tissue Distribution Mediates Tissue-Dependent PPAR Activation and Insulin Sensitization by INT131, a Selective PPAR Modulator. Front Pharmacol. 2017 May 30;8:317. doi: 10.3389/fphar.2017.00317. eCollection 2017.
• [3] INT131: a selective modulator of PPAR gamma. J Mol Biol. 2009 Mar 13;386(5):1301-11. doi: 10.1016/j.jmb.2009.01.025.
• [4] Expression of peroxisome proliferator-activated receptors (PPARs) in human urinary bladder carcinoma and growth inhibition by its agonists. Int J Cancer. 2003 May 1;104(5):597-602.
• [5] Functional PPAR-gamma receptor is a novel therapeutic target for ACTH-secreting pituitary adenomas. Nat Med. 2002 Nov;8(11):1281-7.
• [6] 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.
• [7] Clinical pipeline report, company report or official report of GlaxoSmithKline (2009).
• [8] Peroxisome proliferator-activated receptor alpha activators improve insulin sensitivity and reduce adiposity. J Biol Chem. 2000 Jun 2;275(22):16638-42.
• [9] 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.
• [10] A randomized-controlled trial to investigate the effects of rivoglitazone, a novel PPAR gamma agonist on glucose-lipid control in type 2 diabetes. Diabetes Obes Metab. 2011 Sep;13(9):806-13.
• [11] Balaglitazone: a second generation peroxisome proliferator-activated receptor (PPAR) gamma () agonist.Mini Rev Med Chem.2012 Feb;12(2):87-97.
• [12] 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.
• [13] COX-2 and PPAR-gama confer cannabidiol-induced apoptosis of human lung cancer cells. Mol Cancer Ther. 2013 Jan;12(1):69-82.
• [14] Protective effects of myricitrin against osteoporosis via reducing reactive oxygen species and bone-resorbing cytokines. Toxicol Appl Pharmacol. 2014 Nov 1;280(3):550-60.
• [15] The effect of quercetin and kaempferol aglycones and glucuronides on peroxisome proliferator-activated receptor-gamma (PPAR-). Food Funct. 2015 Apr;6(4):1098-107. doi: 10.1039/c5fo00076a.
• [16] Induction of solid tumor differentiation by the peroxisome proliferator-activated receptor-gamma ligand troglitazone in patients with liposarcoma. Proc Natl Acad Sci U S A. 1999 Mar 30;96(7):3951-6. doi: 10.1073/pnas.96.7.3951.
• [17] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [18] Glucosamine sulfate reduces prostaglandin E(2) production in osteoarthritic chondrocytes through inhibition of microsomal PGE synthase-1. J Rheumatol. 2012 Mar;39(3):635-44. doi: 10.3899/jrheum.110621. Epub 2011 Nov 15.
• [19] Isoniazid suppresses antioxidant response element activities and impairs adipogenesis in mouse and human preadipocytes. Toxicol Appl Pharmacol. 2013 Dec 15;273(3):435-41. doi: 10.1016/j.taap.2013.10.005. Epub 2013 Oct 12.
• [20] Regulatory role of KEAP1 and NRF2 in PPAR expression and chemoresistance in human non-small-cell lung carcinoma cells. Free Radic Biol Med. 2012 Aug 15;53(4):758-68. doi: 10.1016/j.freeradbiomed.2012.05.041. Epub 2012 Jun 7.
• [21] Aspirin inhibits MMP-9 mRNA expression and release via the PPARalpha/gamma and COX-2/mPGES-1-mediated pathways in macrophages derived from THP-1 cells. Biomed Pharmacother. 2010 Feb;64(2):118-23. doi: 10.1016/j.biopha.2009.04.033. Epub 2009 Oct 17.
• [22] Mitochondrial proliferation, DNA depletion and adipocyte differentiation in subcutaneous adipose tissue of HIV-positive HAART recipients. Antivir Ther. 2003 Aug;8(4):323-31.
• [23] Arsenite and cadmium promote the development of mammary tumors. Carcinogenesis. 2020 Jul 14;41(7):1005-1014. doi: 10.1093/carcin/bgz176.
• [24] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [25] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [26] Integrated analysis of rifampicin-induced microRNA and gene expression changes in human hepatocytes. Drug Metab Pharmacokinet. 2014;29(4):333-40.
• [27] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [28] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [29] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [30] Gene expression data from acetaminophen-induced toxicity in human hepatic in vitro systems and clinical liver samples. Data Brief. 2016 Mar 26;7:1052-1057. doi: 10.1016/j.dib.2016.03.069. eCollection 2016 Jun.