Details of the Drug

General Information of Drug (ID: DMGRBN5)

• Drug Name: TESAGLITAZAR
• 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]

• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 1:
  Molecular Weight (mw); 408.5
  Topological Polar Surface Area (xlogp); 3.5
  Rotatable Bond Count (rotbonds); 11
  Hydrogen Bond Donor Count (hbonddonor); 1
  Hydrogen Bond Acceptor Count (hbondacc); 7
• Chemical Identifiers:
  Formula: C20H24O7S
  IUPAC Name: (2S)-2-ethoxy-3-[4-[2-(4-methylsulfonyloxyphenyl)ethoxy]phenyl]propanoic acid
  Canonical SMILES: CCO[C@@H](CC1=CC=C(C=C1)OCCC2=CC=C(C=C2)OS(=O)(=O)C)C(=O)O
  InChI: InChI=1S/C20H24O7S/c1-3-25-19(20(21)22)14-16-6-8-17(9-7-16)26-13-12-15-4-10-18(11-5-15)27-28(2,23)24/h4-11,19H,3,12-14H2,1-2H3,(H,21,22)/t19-/m0/s1
  InChIKey: CXGTZJYQWSUFET-IBGZPJMESA-N
• Cross-matching ID:
  PubChem CID: 208901
  CAS Number: 251565-85-2
  DrugBank ID: DB06536
  TTD ID: D0H1NL

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]

Molecular Expression Atlas of This Drug

• The Studied Disease: Type-1 diabetes
• ICD Disease Classification: 5A10

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Peroxisome proliferator-activated receptor gamma (PPAR-gamma)	DTT	PPARG	2.41E-01	-0.06	-0.25

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] 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.
• [4] Functional PPAR-gamma receptor is a novel therapeutic target for ACTH-secreting pituitary adenomas. Nat Med. 2002 Nov;8(11):1281-7.
• [5] 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.
• [6] Clinical pipeline report, company report or official report of GlaxoSmithKline (2009).
• [7] Peroxisome proliferator-activated receptor alpha activators improve insulin sensitivity and reduce adiposity. J Biol Chem. 2000 Jun 2;275(22):16638-42.
• [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] 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.
• [10] Balaglitazone: a second generation peroxisome proliferator-activated receptor (PPAR) gamma () agonist.Mini Rev Med Chem.2012 Feb;12(2):87-97.
• [11] 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.
• [12] Pemafibrate: First Global Approval. Drugs. 2017 Oct;77(16):1805-1810.
• [13] 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.
• [14] 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.
• [15] 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.
• [16] 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.