Details of the Drug

General Information of Drug (ID: DMQ82T5)

• Drug Name: NS-220
• Synonyms: R-1593; Cis-2-Methyl-5-[4-[5-methyl-2-(4-methylphenyl)oxazol-4-yl]butyl]-1,3-dioxane-2-carboxylic acid

Indication

Disease Entry	ICD 11	Status	REF
Hyperlipidaemia	5C80	Discontinued in Phase 2	[1], [2]

• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 373.4
  Topological Polar Surface Area (xlogp); 4
  Rotatable Bond Count (rotbonds); 7
  Hydrogen Bond Donor Count (hbonddonor); 1
  Hydrogen Bond Acceptor Count (hbondacc); 6
• Chemical Identifiers:
  Formula: C21H27NO5
  IUPAC Name: 2-methyl-5-[4-[5-methyl-2-(4-methylphenyl)-1,3-oxazol-4-yl]butyl]-1,3-dioxane-2-carboxylic acid
  Canonical SMILES: CC1=CC=C(C=C1)C2=NC(=C(O2)C)CCCCC3COC(OC3)(C)C(=O)O
  InChI: InChI=1S/C21H27NO5/c1-14-8-10-17(11-9-14)19-22-18(15(2)27-19)7-5-4-6-16-12-25-21(3,20(23)24)26-13-16/h8-11,16H,4-7,12-13H2,1-3H3,(H,23,24)
  InChIKey: IMYPSTHZBIWMNA-UHFFFAOYSA-N
• Cross-matching ID:
  PubChem CID: 9947731
  TTD ID: D08LZI

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	[3], [4]

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 alpha (PPARA)	DTT	PPARA	1.74E-01	-0.17	-0.3

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: 2678).
• [2] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800017798)
• [3] Modulation of PPAR receptor subtype selectivity of the ligands: aliphatic chain vs aromatic ring as a spacer between pharmacophore and the lipophilic moiety. Bioorg Med Chem Lett. 2008 Dec 15;18(24):6471-5.
• [4] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [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] Peroxisome proliferator-activated receptor alpha activators improve insulin sensitivity and reduce adiposity. J Biol Chem. 2000 Jun 2;275(22):16638-42.
• [7] 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.
• [8] Pemafibrate: First Global Approval. Drugs. 2017 Oct;77(16):1805-1810.
• [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] 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.
• [11] 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.
• [12] Tesaglitazar, a dual PPAR-/ agonist, hamster carcinogenicity, investigative animal and clinical studies.Toxicol Pathol.2012;40(1):18-32.
• [13] 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.