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

General Information of Drug (ID: DMGRBN5)

• Drug Name: TESAGLITAZAR Drug Info
• Synonyms: Tesaglitazar; 251565-85-2; Galida; (S)-2-Ethoxy-3-(4-(4-((methylsulfonyl)oxy)phenethoxy)phenyl)propanoic acid; AZ 242; AZ-242; AR-H039242XX; (S)-2-Ethoxy-3-{4-[2-(4-methanesulfonyloxyphenyl)ethoxy]phenyl}propionic acid; UNII-6734037O3L; (S)-2-Ethoxy-3-{4-[2-(4-methanesulfonyloxy-phenyl)-ethoxy]-phenyl}-propionic acid; (2S)-2-ethoxy-3-[4-[2-(4-methylsulfonyloxyphenyl)ethoxy]phenyl]propanoic acid; BR-44608; 6734037O3L; (S)-2-Ethoxy-3-[4-[2-(4-methanesulfonyloxyphenyl)ethoxy]phenyl]propanoic acid

Indication

Disease Entry	ICD 11	Status	REF
Type-1 diabetes	5A10	Phase 3	[1]

• Cross-matching ID:
  PubChem CID: 208901
  CAS Number: CAS 251565-85-2
  TTD Drug ID: DMGRBN5

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) Targeting Peroxisome proliferator-activated receptor alpha (PPARA)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Lobeglitazone	DMHY3IP	Type-2 diabetes	5A11	Approved	[6]
Fenofibrate	DMFKXDY	Coronary atherosclerosis		Approved	[8]
Bezafibrate	DMZDCS0	Hypercholesterolaemia	5C80.0	Approved	[13]
Ciprofibrate	DMGC5DB	Hyperlipoproteinemia	5C80	Approved	[8]
Pemafibrate	DMD1VZL	Hyperlipidemia	5C80.Z	Approved	[14]
MURAGLITAZAR	DMG3NFZ	N. A.	N. A.	Phase 3	[9]
Ragaglitazar	DMFSHEM	Type-1 diabetes	5A10	Phase 3	[12]
CS-038	DM67P0F	Type-2 diabetes	5A11	Phase 3	[15]
GFT-505	DM7ZOAE	Non-alcoholic steatohepatitis	DB92.1	Phase 3	[16]
ZYH-1	DMMBJYC	Lipid metabolism disorder	5C52.Z	Phase 3	[17]

Drug(s) Affected By Fatty acid-binding protein, liver (FABP1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Sertraline	DM0FB1J	Coronary heart disease	BA80.Z	Approved	[18]
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[19]
Citalopram	DM2G9AE	Acute coronary syndrome	BA41	Approved	[20]
Imipramine	DM2NUH3	Depression	6A70-6A7Z	Approved	[18]
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[21]
Thioridazine	DM35M8J	Schizophrenia	6A20	Approved	[18]
Quercetin	DM3NC4M	Obesity	5B81	Approved	[22]
Fluoxetine	DM3PD2C	Bipolar depression		Approved	[18]
Troglitazone	DM3VFPD	Diabetic complication	5A2Y	Approved	[23]
Erythromycin	DM4K7GQ	Acne vulgaris	ED80	Approved	[24]

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	[25]
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[26]
Quercetin	DM3NC4M	Obesity	5B81	Approved	[27]
Troglitazone	DM3VFPD	Diabetic complication	5A2Y	Approved	[28]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[29]
Glucosamine	DM4ZLFD	Osteoarthritis	FA00-FA05	Approved	[30]
Isoniazid	DM5JVS3	Latent tuberculosis infection		Approved	[31]
Arsenic trioxide	DM61TA4	Acute lymphoblastic leukaemia	2A85	Approved	[32]
Aspirin	DM672AH	Acute coronary syndrome	BA41	Approved	[33]
Stavudine	DM6DEK9	Human immunodeficiency virus infection	1C62	Approved	[34]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Peroxisome proliferator-activated receptor alpha (PPARA)	TTJ584C	PPARA_HUMAN	Modulator	[2]
Peroxisome proliferator-activated receptor gamma (PPAR-gamma)	TTZMAO3	PPARG_HUMAN	Modulator	[2]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Fatty acid-binding protein, liver (FABP1)	OTR34ETM	FABPL_HUMAN	Gene/Protein Processing	[3]
Peroxisome proliferator-activated receptor gamma (PPARG)	OTHMARHO	PPARG_HUMAN	Gene/Protein Processing	[3]

References

• [1] ClinicalTrials.gov (NCT00229710) GALLEX 9: Safety and Tolerability of Oral Tesaglitazar When Added to Insulin Therapy in Patients With Type 2 Diabetes. U.S. National Institutes of Health.
• [2] Tesaglitazar, a dual PPAR-/ agonist, hamster carcinogenicity, investigative animal and clinical studies.Toxicol Pathol.2012;40(1):18-32.
• [3] AZ 242, a novel PPARalpha/gamma agonist with beneficial effects on insulin resistance and carbohydrate and lipid metabolism in ob/ob mice and obese Zucker rats. J Lipid Res. 2002 Nov;43(11):1855-63. doi: 10.1194/jlr.m200127-jlr200.
• [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] 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.
• [14] Pemafibrate: First Global Approval. Drugs. 2017 Oct;77(16):1805-1810.
• [15] 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.
• [16] 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.
• [17] 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.
• [18] A toxicogenomic approach to drug-induced phospholipidosis: analysis of its induction mechanism and establishment of a novel in vitro screening system. Toxicol Sci. 2005 Feb;83(2):282-92.
• [19] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [20] In vitro detection of drug-induced phospholipidosis using gene expression and fluorescent phospholipid based methodologies. Toxicol Sci. 2007 Sep;99(1):162-73.
• [21] The contribution of methotrexate exposure and host factors on transcriptional variance in human liver. Toxicol Sci. 2007 Jun;97(2):582-94.
• [22] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [23] Species-specific toxicity of diclofenac and troglitazone in primary human and rat hepatocytes. Chem Biol Interact. 2009 Apr 15;179(1):17-24.
• [24] Determination of phospholipidosis potential based on gene expression analysis in HepG2 cells. Toxicol Sci. 2007 Mar;96(1):101-14.
• [25] COX-2 and PPAR-gama confer cannabidiol-induced apoptosis of human lung cancer cells. Mol Cancer Ther. 2013 Jan;12(1):69-82.
• [26] 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.
• [27] 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.
• [28] 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.
• [29] 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.
• [30] 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.
• [31] 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.
• [32] 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.
• [33] 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.
• [34] Mitochondrial proliferation, DNA depletion and adipocyte differentiation in subcutaneous adipose tissue of HIV-positive HAART recipients. Antivir Ther. 2003 Aug;8(4):323-31.