Details of the Drug

General Information of Drug (ID: DMRTD16)

• Drug Name: talinolol
• Synonyms: Talinolol; 57460-41-0; Cordanum; Racemic talinolol; 1-(4-(3-(TERT-BUTYLAMINO)-2-HYDROXYPROPOXY)PHENYL)-3-CYCLOHEXYLUREA; Talinolol [INN]; (+-)-Talinolol; Talinololum [INN-Latin]; 38649-73-9; 1-(4-Cyclohexylureidophenoxy)-2-hydroxy-3-tert-butylaminopropane; Talinolol (INN); (+-)-N-Cyclohexyl-N'-(4-(3-((1,1-dimethylethyl)amino)-2-hydroxypropoxy)phenyl)urea; NCGC00164542-01; 1-(4-(cyclohexylureido)phenoxy)-3-(tert-butylamino)-2-propanol; 1-(3-(3-Cyclohexylureido)phenoxy)-3-(tert-butylamino)-2-propanol

Indication

Disease Entry	ICD 11	Status	REF
Discovery agent	N.A.	Investigative	[1]

• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 363.5
  Logarithm of the Partition Coefficient (xlogp); 2.6
  Rotatable Bond Count (rotbonds); 8
  Hydrogen Bond Donor Count (hbonddonor); 4
  Hydrogen Bond Acceptor Count (hbondacc); 4
• ADMET Property:
  BDDCS Class: Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 3: high solubility and low permeability [2]
  Bioavailability: 55% of drug becomes completely available to its intended biological destination(s) [3]
  Clearance: The drug present in the plasma can be removed from the body at the rate of 4.9 mL/min/kg [4]
  Elimination: 52.8% of drug is excreted from urine in the unchanged form [2]
  Half-life: The concentration or amount of drug in body reduced by one-half in 11 hours [4]
  Unbound Fraction: The unbound fraction of drug in plasma is 0.39% [4]
  Vd: Fluid volume that would be required to contain the amount of drug present in the body at the same concentration as in the plasma 3.3 L/kg [4]
  Water Solubility: The ability of drug to dissolve in water is measured as 1.23 mg/mL [2]
• Chemical Identifiers:
  Formula: C20H33N3O3
  IUPAC Name: 1-[4-[3-(tert-butylamino)-2-hydroxypropoxy]phenyl]-3-cyclohexylurea
  Canonical SMILES: CC(C)(C)NCC(COC1=CC=C(C=C1)NC(=O)NC2CCCCC2)O
  InChI: InChI=1S/C20H33N3O3/c1-20(2,3)21-13-17(24)14-26-18-11-9-16(10-12-18)23-19(25)22-15-7-5-4-6-8-15/h9-12,15,17,21,24H,4-8,13-14H2,1-3H3,(H2,22,23,25)
  InChIKey: MXFWWQICDIZSOA-UHFFFAOYSA-N
• Cross-matching ID:
  PubChem CID: 68770
  ChEBI ID: CHEBI:135533
  CAS Number: 57460-41-0
  DrugBank ID: DB11770
  TTD ID: D05JKG
  VARIDT ID: DR00401
  INTEDE ID: DR1527

Molecular Interaction Atlas of This Drug

Drug Transporter (DTP)

DTP Name	DTP ID	UniProt ID	MOA	REF
Multidrug resistance-associated protein 2 (ABCC2)	DTFI42L	MRP2_HUMAN	Substrate	[5]
Organic anion transporting polypeptide 2B1 (SLCO2B1)	DTPFTEQ	SO2B1_HUMAN	Substrate	[6]
Organic anion transporting polypeptide 1A2 (SLCO1A2)	DTE2B1D	SO1A2_HUMAN	Substrate	[7]
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[8]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 3A4 (CYP3A4) Main DME	DE4LYSA	CP3A4_HUMAN	Substrate	[9]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Solute carrier organic anion transporter family member 1B1 (SLCO1B1)	OTNEN8QK	SO1B1_HUMAN	Drug Response	[10]

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: 4664).
• [2] BDDCS applied to over 900 drugs
• [3] Critical Evaluation of Human Oral Bioavailability for Pharmaceutical Drugs by Using Various Cheminformatics Approaches
• [4] Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
• [5] FDA Drug Development and Drug Interactions
• [6] Species difference in the effect of grapefruit juice on intestinal absorption of talinolol between human and rat. J Pharmacol Exp Ther. 2010 Jan;332(1):181-9.
• [7] Concentration-dependent effect of naringin on intestinal absorption of beta(1)-adrenoceptor antagonist talinolol mediated by p-glycoprotein and organic anion transporting polypeptide (Oatp). Pharm Res. 2009 Mar;26(3):560-7.
• [8] Grapefruit juice-drug interactions: Grapefruit juice and its components inhibit P-glycoprotein (ABCB1) mediated transport of talinolol in Caco-2 cells. J Pharm Sci. 2007 Oct;96(10):2808-17.
• [9] Stereoselective disposition of talinolol in man. J Pharm Sci. 2002 Feb;91(2):303-11.
• [10] Simvastatin does not influence the intestinal P-glycoprotein and MPR2, and the disposition of talinolol after chronic medication in healthy subjects genotyped for the ABCB1, ABCC2 and SLCO1B1 polymorphisms. Br J Clin Pharmacol. 2006 Apr;61(4):440-50. doi: 10.1111/j.1365-2125.2006.02599.x.