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

General Information of Drug (ID: DMTG18I)

• Drug Name: Aleglitazar Drug Info
• Synonyms: RO7; Aleglitazar (USAN); 2-methoxy-3-[4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]benzothiophen-7-yl]propanoic Acid

Indication

Disease Entry	ICD 11	Status	REF
Type-2 diabetes	5A11	Discontinued in Phase 3	[1]

• Cross-matching ID:
  PubChem CID: 10274777
  CAS Number: CAS 475479-34-6
  TTD Drug ID: DMTG18I
  INTEDE Drug ID: DR1792

Molecule-Related Drug Atlas

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	[4]
Fenofibrate	DMFKXDY	Coronary atherosclerosis		Approved	[5]
Bezafibrate	DMZDCS0	Hypercholesterolaemia	5C80.0	Approved	[6]
Ciprofibrate	DMGC5DB	Hyperlipoproteinemia	5C80	Approved	[5]
Pemafibrate	DMD1VZL	Hyperlipidemia	5C80.Z	Approved	[7]
MURAGLITAZAR	DMG3NFZ	N. A.	N. A.	Phase 3	[8]
Ragaglitazar	DMFSHEM	Type-1 diabetes	5A10	Phase 3	[9]
CS-038	DM67P0F	Type-2 diabetes	5A11	Phase 3	[10]
TESAGLITAZAR	DMGRBN5	Type-1 diabetes	5A10	Phase 3	[11]
GFT-505	DM7ZOAE	Non-alcoholic steatohepatitis	DB92.1	Phase 3	[12]

Drug(s) Metabolized By Cytochrome P450 2C8 (CYP2C8)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Fluorouracil	DMUM7HZ	Adenocarcinoma	2D40	Approved	[13]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[14]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[14]
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[15]
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[16]
Diclofenac	DMPIHLS	Chronic renal failure	GB61.Z	Approved	[17]
Sorafenib	DMS8IFC	Adenocarcinoma	2D40	Approved	[18]
Quinine	DMSWYF5	Malaria	1F40-1F45	Approved	[14]
Mycophenolate mofetil	DMPQAGE	Hepatosplenic T-cell lymphoma		Approved	[19]
Propofol	DMB4OLE	Anaesthesia	9A78.6	Approved	[20]

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	Agonist	[2]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 2C8 (CYP2C8) Main DME	DES5XRU	CP2C8_HUMAN	Substrate	[3]

References

• [1] 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. (Ligand id: 7405).
• [2] Clinical pipeline report, company report or official report of Roche (2009).
• [3] Exposure and response analysis of aleglitazar on cardiovascular risk markers and safety outcomes: an analysis of the AleCardio trial. Diabetes Obes Metab. 2020 Jan;22(1):30-38.
• [4] 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.
• [5] Peroxisome proliferator-activated receptor alpha activators improve insulin sensitivity and reduce adiposity. J Biol Chem. 2000 Jun 2;275(22):16638-42.
• [6] 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.
• [7] Pemafibrate: First Global Approval. Drugs. 2017 Oct;77(16):1805-1810.
• [8] 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.
• [9] 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.
• [10] 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.
• [11] Tesaglitazar, a dual PPAR-/ agonist, hamster carcinogenicity, investigative animal and clinical studies.Toxicol Pathol.2012;40(1):18-32.
• [12] 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.
• [13] Roles of cytochromes P450 1A2, 2A6, and 2C8 in 5-fluorouracil formation from tegafur, an anticancer prodrug, in human liver microsomes. Drug Metab Dispos. 2000 Dec;28(12):1457-63.
• [14] Role of cytochrome P450 2C8 in drug metabolism and interactions. Pharmacol Rev. 2016 Jan;68(1):168-241.
• [15] Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448.
• [16] Differential expression and function of CYP2C isoforms in human intestine and liver. Pharmacogenetics. 2003 Sep;13(9):565-75.
• [17] Analysis of human cytochrome P450 2C8 substrate specificity using a substrate pharmacophore and site-directed mutants. Biochemistry. 2004 Dec 14;43(49):15379-92.
• [18] Interaction of sorafenib and cytochrome P450 isoenzymes in patients with advanced melanoma: a phase I/II pharmacokinetic interaction study. Cancer Chemother Pharmacol. 2011 Nov;68(5):1111-8.
• [19] PharmGKB summary: mycophenolic acid pathway. Pharmacogenet Genomics. 2014 Jan;24(1):73-9.
• [20] Possible involvement of multiple human cytochrome P450 isoforms in the liver metabolism of propofol. Br J Anaesth. 1998 Jun;80(6):788-95.