Details of the Drug

General Information of Drug (ID: DMHR8KW)

Drug Name
Alvimopan
Synonyms
Alvimopan anhydrous; LY 246736; LY246736; Adl 8-2698; Entereg (TN); Trans-3,4-dimethyl-4-(3-hydroxyphenyl) piperidine; Glycine, N-[2-[[4-(3-hydroxyphenyl)-3,4-dimethyl-1-piperidinyl]methyl]-1-oxo-3-phenylpropyl; 2-[[(2S)-2-benzyl-3-[(3R,4R)-4-(3-hydroxyphenyl)-3,4-dimethylpiperidin-1-yl]propanoyl]amino]acetic acid
Indication
Disease Entry ICD 11 Status REF
Gastrointestinal disease DE2Z Approved [1], [2], [3]
Therapeutic Class
Analgesics
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 0 Molecular Weight (mw) 424.5
Topological Polar Surface Area (xlogp) 1.7
Rotatable Bond Count (rotbonds) 8
Hydrogen Bond Donor Count (hbonddonor) 3
Hydrogen Bond Acceptor Count (hbondacc) 5
ADMET Property
BDDCS Class
Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 3: high solubility and low permeability [4]
Clearance
The clearance of drug is 402 +/- 89 mL/min [5]
Elimination
2% of drug is excreted from urine in the unchanged form [4]
Half-life
The concentration or amount of drug in body reduced by one-half in 10 - 17 hours [6]
Metabolism
The drug is metabolized via the intestinal flora to an active metabolite [7]
MRTD
The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 0.8076 micromolar/kg/day [8]
Unbound Fraction
The unbound fraction of drug in plasma is 0.2% [6]
Vd
The volume of distribution (Vd) of drug is 30 +/- 10 L [5]
Water Solubility
The ability of drug to dissolve in water is measured as 0.1 mg/mL [4]
Chemical Identifiers
Formula
C25H32N2O4
IUPAC Name
2-[[(2S)-2-benzyl-3-[(3R,4R)-4-(3-hydroxyphenyl)-3,4-dimethylpiperidin-1-yl]propanoyl]amino]acetic acid
Canonical SMILES
C[C@H]1CN(CC[C@@]1(C)C2=CC(=CC=C2)O)C[C@H](CC3=CC=CC=C3)C(=O)NCC(=O)O
InChI
InChI=1S/C25H32N2O4/c1-18-16-27(12-11-25(18,2)21-9-6-10-22(28)14-21)17-20(24(31)26-15-23(29)30)13-19-7-4-3-5-8-19/h3-10,14,18,20,28H,11-13,15-17H2,1-2H3,(H,26,31)(H,29,30)/t18-,20-,25+/m0/s1
InChIKey
UPNUIXSCZBYVBB-JVFUWBCBSA-N
Cross-matching ID
PubChem CID
5488548
ChEBI ID
CHEBI:135686
CAS Number
156053-89-3
DrugBank ID
DB06274
TTD ID
D0D7KC
ACDINA ID
D00026

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Opioid receptor mu (MOP) TTKWM86 OPRM_HUMAN Antagonist [9]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease Gastrointestinal disease
ICD Disease Classification DE2Z
Molecule Name Molecule Type Gene Name p-value Fold-Change Z-score
Opioid receptor mu (MOP) DTT OPRM1 5.94E-01 -0.02 -0.17
Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This Drug

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Alvimopan (Comorbidity)
DDI Drug Name DDI Drug ID Severity Mechanism Comorbidity REF
Enzalutamide DMGL19D Moderate Accelerated clearance of Alvimopan due to the transporter induction by Enzalutamide. Prostate cancer [2C82] [19]
Fostamatinib DM6AUHV Moderate Decreased clearance of Alvimopan due to the transporter inhibition by Fostamatinib. Thrombocytopenia [3B64] [20]

Drug Inactive Ingredient(s) (DIG) and Formulation(s) of This Drug

DIG
DIG Name DIG ID PubChem CID Functional Classification
Polyethylene glycol 3350 E00652 Not Available Coating agent; Diluent; Ointment base; Plasticizing agent; Solvent; Suppository base; lubricant
Pharmaceutical Formulation
Formulation Name Drug Dosage Dosage Form Route
Alvimopan 12 mg capsule 12 mg Oral Capsule Oral
Jump to Detail Pharmaceutical Formulation Page of This Drug

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: 7471).
2 2008 FDA drug approvals. Nat Rev Drug Discov. 2009 Feb;8(2):93-6.
3 Emerging drugs for postoperative ileus. Expert Opin Emerg Drugs. 2007 Nov;12(4):619-26.
4 BDDCS applied to over 900 drugs
5 An FDA phase I clinical trial of quinacrine sterilization (QS). Int J Gynaecol Obstet. 2003 Oct;83 Suppl 2:S45-9.
6 Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
7 FDA approval: ado-trastuzumab emtansine for the treatment of patients with HER2-positive metastatic breast cancer. Clin Cancer Res. 2014 Sep 1;20(17):4436-41.
8 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
9 Alvimopan for postoperative ileus. Am J Health Syst Pharm. 2009 Jul 15;66(14):1267-77.
10 Buprenorphine is a weak partial agonist that inhibits opioid receptor desensitization. J Neurosci. 2009 Jun 3;29(22):7341-8.
11 Antianalgesia: stereoselective action of dextro-morphine over levo-morphine on glia in the mouse spinal cord.J Pharmacol Exp Ther.2005 Sep;314(3):1101-8.
12 Clinical pipeline report, company report or official report of signaturerx.
13 The ChEMBL database in 2017. Nucleic Acids Res. 2017 Jan 4;45(D1):D945-D954.
14 Concentration-effect relationship of intravenous alfentanil and ketamine on peripheral neurosensory thresholds, allodynia and hyperalgesia of neuropathic pain. Pain. 2001 Mar;91(1-2):177-87.
15 2014 FDA drug approvals. Nat Rev Drug Discov. 2015 Feb;14(2):77-81.
16 Molecular characterization of eluxadoline as a potential ligand targeting mu-delta opioid receptor heteromers.Biochem Pharmacol.2014 Dec 1;92(3):448-56.
17 Drug design and synthesis of a novel kappa opioid receptor agonist with an oxabicyclo[2.2.2]octane skeleton and its pharmacology. Bioorg Med Chem Lett. 2010 Jan 1;20(1):121-4.
18 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. (Target id: 319).
19 Benoist G, van Oort I, et al "Drug-drug interaction potential in men treated with enzalutamide: Mind the gap." Br J Clin Pharmacol 0 (2017): epub. [PMID: 28881501]
20 Product Information. Tavalisse (fostamatinib). Rigel Pharmaceuticals, South San Francisco, CA.