Details of the Drug

General Information of Drug (ID: DMBU9O4)

• Drug Name: KRP-101
• Synonyms: PPAR alpha agonist (hyperlipidemia), Kyorin

Indication

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

• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 451.5
  Topological Polar Surface Area (xlogp); 5
  Rotatable Bond Count (rotbonds); 10
  Hydrogen Bond Donor Count (hbonddonor); 2
  Hydrogen Bond Acceptor Count (hbondacc); 6
• Chemical Identifiers:
  Formula: C26H26FNO5
  IUPAC Name: (2S)-2-[[3-[[4-(4-fluorophenoxy)phenyl]methylcarbamoyl]-4-methoxyphenyl]methyl]butanoic acid
  Canonical SMILES: CC[C@@H](CC1=CC(=C(C=C1)OC)C(=O)NCC2=CC=C(C=C2)OC3=CC=C(C=C3)F)C(=O)O
  InChI: InChI=1S/C26H26FNO5/c1-3-19(26(30)31)14-18-6-13-24(32-2)23(15-18)25(29)28-16-17-4-9-21(10-5-17)33-22-11-7-20(27)8-12-22/h4-13,15,19H,3,14,16H2,1-2H3,(H,28,29)(H,30,31)/t19-/m0/s1
  InChIKey: VRHOBXXCNBZJRX-IBGZPJMESA-N
• Cross-matching ID:
  PubChem CID: 9825046
  CAS Number: 311770-26-0
  TTD ID: D0B8JQ

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], [3]

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] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800018628)
• [2] Identification of a functional peroxisome proliferator-activated receptor (PPAR) response element (PPRE) in the human apolipoprotein A-IV gene. Biochem Pharmacol. 2009 Sep 1;78(5):523-30.
• [3] A novel PPARalpha agonist ameliorates insulin resistance in dogs fed a high-fat diet. Am J Physiol Endocrinol Metab. 2008 May;294(5):E833-40.
• [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.