Details of the Drug

General Information of Drug (ID: DML1VXW)

• Drug Name: Arotinolol
• Synonyms: Arotinolol; Arotinolol (INN); Arotinolol [INN]; Arotinololum; Arotinololum [Latin]; (+-)-5-(2-((3-(tert-Butylamino)-2-hydroxypropyl)thio)-4-thiazolyl)-2-thiophenecarboxamide; 2-(3-tert-Butylamino-2-hydroxypropylthio)-4-(5-carbamoyl-2-thienyl)thiazole; 5-(2-((3-(tert-Butylamino)-2-hydroxypropyl)thio)thiazol-4-yl)thiophene-2-carboxamide; 5-[2-[3-(tert-butylamino)-2-hydroxypropyl]sulfanyl-1,3-thiazol-4-yl]thiophene-2-carboxamide; 68377-92-4; AK129719; C15H21N3O2S3; S-596

Indication

Disease Entry	ICD 11	Status	REF
Essential tremor or related tremors	8A04.1	Phase 4	[1]

• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 371.5
  Topological Polar Surface Area (xlogp); 2.3
  Rotatable Bond Count (rotbonds); 8
  Hydrogen Bond Donor Count (hbonddonor); 3
  Hydrogen Bond Acceptor Count (hbondacc); 7
• ADMET Property:
  Absorption Tmax: The time to maximum plasma concentration (Tmax) is 2 h [2]
  Half-life: The concentration or amount of drug in body reduced by one-half in 7.2 hours [3]
• Chemical Identifiers:
  Formula: C15H21N3O2S3
  IUPAC Name: 5-[2-[3-(tert-butylamino)-2-hydroxypropyl]sulfanyl-1,3-thiazol-4-yl]thiophene-2-carboxamide
  Canonical SMILES: CC(C)(C)NCC(CSC1=NC(=CS1)C2=CC=C(S2)C(=O)N)O
  InChI: BHIAIPWSVYSKJS-UHFFFAOYSA-N
  InChIKey: 1S/C15H21N3O2S3/c1-15(2,3)17-6-9(19)7-21-14-18-10(8-22-14)11-4-5-12(23-11)13(16)20/h4-5,8-9,17,19H,6-7H2,1-3H3,(H2,16,20)
• Cross-matching ID:
  PubChem CID: 2239
  ChEBI ID: CHEBI:135569
  CAS Number: 68377-92-4
  DrugBank ID: DB09204
  INTEDE ID: DR0138

Molecular Interaction Atlas of This Drug

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 2D6 (CYP2D6) Main DME	DECB0K3	CP2D6_HUMAN	Substrate	[4]

References

• [1] ClinicalTrials.gov (NCT02612298) Efficacy and Safety of Arotinolol Hydrochloride on Morning Blood Pressure and Heart Rate.
• [2] Nakashima M, Uematsu T, Takiguchi Y, Hashimoto H, Watanabe I, Morioka S, Hibino T: Effect of ophthalmic administration of S-596 (Arotinolol) on intraocular pressure and haemodynamics in health volunteers: comparison with timolol. Eur J Clin Pharmacol. 1985;28(4):391-6.
• [3] Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
• [4] Application of substrate depletion assay to evaluation of CYP isoforms responsible for stereoselective metabolism of carvedilol. Drug Metab Pharmacokinet. 2016 Dec;31(6):425-432.
• [5] Inhibitory effects of anticancer drugs on dextromethorphan-O-demethylase activity in human liver microsomes. Cancer Chemother Pharmacol. 1993;32(6):491-5.
• [6] Effect of genetic polymorphism on the metabolism of endogenous neuroactive substances, progesterone and p-tyramine, catalyzed by CYP2D6. Brain Res Mol Brain Res. 2004 Oct 22;129(1-2):117-23.
• [7] CYP2D6 polymorphisms and tamoxifen metabolism: clinical relevance. Curr Oncol Rep. 2010 Jan;12(1):7-15.
• [8] Metabolic interactions between acetaminophen (paracetamol) and two flavonoids, luteolin and quercetin, through in-vitro inhibition studies. J Pharm Pharmacol. 2017 Dec;69(12):1762-1772.
• [9] Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675.
• [10] Inhibition of cytochrome P450 2D6: structure-activity studies using a series of quinidine and quinine analogues. Chem Res Toxicol. 2003 Apr;16(4):450-9.
• [11] Effects of propofol on human hepatic microsomal cytochrome P450 activities. Xenobiotica. 1998 Sep;28(9):845-53.
• [12] Pharmacogenetics of schizophrenia. Am J Med Genet. 2000 Spring;97(1):98-106.
• [13] Roles of CYP2A6 and CYP2B6 in nicotine C-oxidation by human liver microsomes. Arch Toxicol. 1999 Mar;73(2):65-70.
• [14] Structure-activity relationship for human cytochrome P450 substrates and inhibitors. Drug Metab Rev. 2002 Feb-May;34(1-2):69-82.