Details of the Drug

General Information of Drug (ID: DMFNTMY)

• Drug Name: Fibrates
• Synonyms: clofibric acid; 882-09-7; 2-(4-Chlorophenoxy)-2-methylpropanoic acid; Chlorofibrinic acid; Clofibrinic acid; Chlorfibrinic acid; Clofibrin; 2-(4-CHLOROPHENOXY)-2-METHYLPROPIONIC ACID; Chlorophibrinic acid; PCIB; Clofibrate free acid; Clofibrinsaeure; Regulipid; Regadrin; PCPIB; 2-(p-Chlorophenoxy)-2-methylpropionic acid; 2-(4-Chlorophenoxy)isobutyric Acid; 4-CPIB; 2-(p-Chlorophenoxy)isobutyric acid; Propanoic acid, 2-(4-chlorophenoxy)-2-methyl-; alpha-(p-Chlorophenoxy)isobutyric acid; Acido clofibrico; Acide clofibrique; Acidum c

Indication

Disease Entry	ICD 11	Status	REF
Dyslipidemia	5C80-5C81	Investigative	[1]

• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 214.64
  Topological Polar Surface Area (xlogp); 2.6
  Rotatable Bond Count (rotbonds); 3
  Hydrogen Bond Donor Count (hbonddonor); 1
  Hydrogen Bond Acceptor Count (hbondacc); 3
• ADMET Property:
  BDDCS Class: Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 1: high solubility and high permeability [2]
  Elimination: 5.7% of drug is excreted from urine in the unchanged form [2]
  MRTD: The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 155.136 micromolar/kg/day [3]
  Water Solubility: The ability of drug to dissolve in water is measured as 45 mg/mL [2]
• Chemical Identifiers:
  Formula: C10H11ClO3
  IUPAC Name: 2-(4-chlorophenoxy)-2-methylpropanoic acid
  Canonical SMILES: CC(C)(C(=O)O)OC1=CC=C(C=C1)Cl
  InChI: InChI=1S/C10H11ClO3/c1-10(2,9(12)13)14-8-5-3-7(11)4-6-8/h3-6H,1-2H3,(H,12,13)
  InChIKey: TXCGAZHTZHNUAI-UHFFFAOYSA-N
• Cross-matching ID:
  PubChem CID: 2797
  ChEBI ID: CHEBI:34648
  CAS Number: 882-09-7
  TTD ID: D06RRD

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	[1]

Molecular Expression Atlas of This Drug

• The Studied Disease: Dyslipidemia
• ICD Disease Classification: 5C80-5C81

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] Emerging antidyslipidemic drugs. Expert Opin Emerg Drugs. 2008 Jun;13(2):363-81.
• [2] BDDCS applied to over 900 drugs
• [3] Estimating the safe starting dose in phase I clinical trials and no observed effect level based on QSAR modeling of the human maximum recommended daily dose
• [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.