Details of the Drug

General Information of Drug (ID: DMJWR1I)

• Drug Name: E-3030
• Synonyms: Dual PPAR alpha/gamma agonists, Eisai

Indication

Disease Entry	ICD 11	Status	REF
Hyperlipidaemia	5C80	Discontinued in Phase 1	[1]

• #Ro5 Violations (Lipinski): 3:
  Molecular Weight; 909.8
  Topological Polar Surface Area; Not Available
  Rotatable Bond Count; 20
  Hydrogen Bond Donor Count; 0
  Hydrogen Bond Acceptor Count; 14
• Chemical Identifiers:
  Formula: C44H44CaCl2F2N2O10
  IUPAC Name: calcium;(2S)-3-[3-[(2S)-3-(4-chloro-2-cyanophenoxy)-2-fluoropropoxy]phenyl]-2-propan-2-yloxypropanoate
  Canonical SMILES: CC(C)O[C@@H](CC1=CC(=CC=C1)OC[C@@H](COC2=C(C=C(C=C2)Cl)C#N)F)C(=O)[O-].CC(C)O[C@@H](CC1=CC(=CC=C1)OC[C@@H](COC2=C(C=C(C=C2)Cl)C#N)F)C(=O)[O-].[Ca+2]
  InChI: InChI=1S/2C22H23ClFNO5.Ca/c2*1-14(2)30-21(22(26)27)9-15-4-3-5-19(8-15)28-12-18(24)13-29-20-7-6-17(23)10-16(20)11-25;/h2*3-8,10,14,18,21H,9,12-13H2,1-2H3,(H,26,27);/q;;+2/p-2/t2*18-,21-;/m00./s1
  InChIKey: QBPOEQDRFVFZRI-ATAMATRTSA-L
• Cross-matching ID:
  PubChem CID: 11949481
  CAS Number: 913722-93-7
  TTD ID: D06PHO

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: Hyperlipidaemia
• ICD Disease Classification: 5C80

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] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800021476)
• [2] Antidiabetic and hypolipidemic effects of a novel dual peroxisome proliferator-activated receptor (PPAR) alpha/gamma agonist, E3030, in db/db mice and beagle dogs.J Pharmacol Sci.2008 Sep;108(1):40-8.
• [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] Tesaglitazar, a dual PPAR-/ agonist, hamster carcinogenicity, investigative animal and clinical studies.Toxicol Pathol.2012;40(1):18-32.
• [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.