Details of the Drug

General Information of Drug (ID: DMND3AB)

• Drug Name: Asimadoline
• Synonyms: Asimadoline [INN]; EMD 61753; N-[(1S)-2-[(3S)-3-hydroxypyrrolidin-1-yl]-1-phenylethyl]-N-methyl-2,2-diphenylacetamide

Indication

Disease Entry	ICD 11	Status	REF
Diarrhea-predominant irritable bowel syndrome	DD91.01	Phase 3	[1]
Pruritus	EC90	Phase 2	[2]

• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 414.5
  Topological Polar Surface Area (xlogp); 4.1
  Rotatable Bond Count (rotbonds); 7
  Hydrogen Bond Donor Count (hbonddonor); 1
  Hydrogen Bond Acceptor Count (hbondacc); 3
• Chemical Identifiers:
  Formula: C27H30N2O2
  IUPAC Name: N-[(1S)-2-[(3S)-3-hydroxypyrrolidin-1-yl]-1-phenylethyl]-N-methyl-2,2-diphenylacetamide
  Canonical SMILES: CN([C@H](CN1CC[C@@H](C1)O)C2=CC=CC=C2)C(=O)C(C3=CC=CC=C3)C4=CC=CC=C4
  InChI: InChI=1S/C27H30N2O2/c1-28(25(21-11-5-2-6-12-21)20-29-18-17-24(30)19-29)27(31)26(22-13-7-3-8-14-22)23-15-9-4-10-16-23/h2-16,24-26,30H,17-20H2,1H3/t24-,25+/m0/s1
  InChIKey: JHLHNYVMZCADTC-LOSJGSFVSA-N
• Cross-matching ID:
  PubChem CID: 179340
  CAS Number: 153205-46-0
  DrugBank ID: DB05104
  TTD ID: D07TQN
  VARIDT ID: DR01267

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Opioid receptor kappa (OPRK1)	TTQW87Y	OPRK_HUMAN	Agonist	[1]

Drug Transporter (DTP)

DTP Name	DTP ID	UniProt ID	MOA	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[3]

Molecular Expression Atlas of This Drug

• The Studied Disease: Diarrhea-predominant irritable bowel syndrome
• ICD Disease Classification: DD91.01

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Opioid receptor kappa (OPRK1)	DTT	OPRK1	9.17E-01	0.04	0.1
P-glycoprotein 1 (ABCB1)	DTP	P-GP	9.26E-01	-3.59E-03	-1.34E-02

References

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• [5] MDR1 (ABCB1) G1199A (Ser400Asn) polymorphism alters transepithelial permeability and sensitivity to anticancer agents. Cancer Chemother Pharmacol. 2009 Jun;64(1):183-8.
• [6] Folate transporter expression decreases in the human placenta throughout pregnancy and in pre-eclampsia. Pregnancy Hypertens. 2012 Apr;2(2):123-31.
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• [9] Association of genetic polymorphisms in the influx transporter SLCO1B3 and the efflux transporter ABCB1 with imatinib pharmacokinetics in patients with chronic myeloid leukemia. Ther Drug Monit. 2011 Apr;33(2):244-50.
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• [12] In silico identification and biochemical evaluation of novel inhibitors of NRH:quinone oxidoreductase 2 (NQO2). Bioorg Med Chem Lett. 2010 Dec 15;20(24):7331-6.
• [13] Pharmacological profiles of opioid ligands at kappa opioid receptors. BMC Pharmacol. 2006 Jan 25;6:3.
• [14] Nalbuphine: an autoradiographic opioid receptor binding profile in the central nervous system of an agonist/antagonist analgesic. J Pharmacol Exp Ther. 1988 Jan;244(1):391-402.
• [15] Peptide Kappa Opioid Receptor Ligands: Potential for Drug Development. AAPS J. 2009 June; 11(2): 312-322.
• [16] Wax PM, Becker CE, Curry SC: Unexpected gas casualties in Moscow: a medical toxicology perspective. Ann Emerg Med. 2003 May;41(5):700-5.
• [17] Molecular Mechanisms of Opioid Receptor-Dependent Signaling and Behavior. Anesthesiology. 2011 December; 115(6): 1363-1381.
• [18] Novel developments with selective, non-peptidic kappa-opioid receptor agonists. Expert Opin Investig Drugs. 1997 Oct;6(10):1351-68.