Details of the Drug

General Information of Drug (ID: DM26IH8)

Drug Name
S-297995
Synonyms
NALDEMEDINE; UNII-03KSI6WLXH; 03KSI6WLXH; S-297,995; 916072-89-4; Naldemedine [USAN:INN]; Naldemedine (USAN/INN); S 297995; SCHEMBL9880572; GTPL9150; CHEMBL2105755; AKOS032945757; DB11691; Morphinan-7-carboxamide, 17-(cyclopropylmethyl)-6,7-didehydro-4,5-epoxy-3,6,14- trihydroxy-N-(1-methyl-1-(3-phenyl-1,2,4-oxadiazol-5-yl)ethyl)-,(5alpha)-; J3.573.009E; D10188
Indication
Disease Entry ICD 11 Status REF
Opioid dependence 6C43.2Z Phase 2 [1]
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 1 Molecular Weight (mw) 570.6
Logarithm of the Partition Coefficient (xlogp) 3.2
Rotatable Bond Count (rotbonds) 6
Hydrogen Bond Donor Count (hbonddonor) 4
Hydrogen Bond Acceptor Count (hbondacc) 9
ADMET Property
Absorption Tmax
The time to maximum plasma concentration (Tmax) is 0.75 h []
Elimination
57% of naldemedine is excreted in the urine with 16-18% as the parent compound and 35% is excreted in the feces []
Half-life
The concentration or amount of drug in body reduced by one-half in 11 hours []
Metabolism
The drug is metabolized via the CYP3A []
Vd
The volume of distribution (Vd) of drug is 155 L []
Chemical Identifiers
Formula
C32H34N4O6
IUPAC Name
(4R,4aS,7aR,12bS)-3-(cyclopropylmethyl)-4a,7,9-trihydroxy-N-[2-(3-phenyl-1,2,4-oxadiazol-5-yl)propan-2-yl]-1,2,4,5,7a,13-hexahydro-4,12-methanobenzofuro[3,2-e]isoquinoline-6-carboxamide
Canonical SMILES
CC(C)(C1=NC(=NO1)C2=CC=CC=C2)NC(=O)C3=C([C@H]4[C@@]56CCN([C@@H]([C@@]5(C3)O)CC7=C6C(=C(C=C7)O)O4)CC8CC8)O
InChI
InChI=1S/C32H34N4O6/c1-30(2,29-33-27(35-42-29)18-6-4-3-5-7-18)34-28(39)20-15-32(40)22-14-19-10-11-21(37)25-23(19)31(32,26(41-25)24(20)38)12-13-36(22)16-17-8-9-17/h3-7,10-11,17,22,26,37-38,40H,8-9,12-16H2,1-2H3,(H,34,39)/t22-,26+,31+,32-/m1/s1
InChIKey
AXQACEQYCPKDMV-RZAWKFBISA-N
Cross-matching ID
PubChem CID
54732242
CAS Number
916072-89-4
DrugBank ID
DB11691
TTD ID
D0Q3PD
ACDINA ID
D00453

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Opioid receptor (OPR) TTN4QDT NOUNIPROTAC Antagonist [1]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from S-297995 (Comorbidity)
DDI Drug Name DDI Drug ID Severity Mechanism Comorbidity REF
Arn-509 DMT81LZ Major Increased metabolism of S-297995 caused by Arn-509 mediated induction of CYP450 enzyme. Acute myeloid leukaemia [2A60] [2]
Gilteritinib DMTI0ZO Moderate Decreased clearance of S-297995 due to the transporter inhibition by Gilteritinib. Acute myeloid leukaemia [2A60] [3]
Troleandomycin DMUZNIG Moderate Decreased metabolism of S-297995 caused by Troleandomycin mediated inhibition of CYP450 enzyme. Bacterial infection [1A00-1C4Z] [4]
Erdafitinib DMI782S Moderate Decreased clearance of S-297995 due to the transporter inhibition by Erdafitinib. Bladder cancer [2C94] [5]
Pexidartinib DMS2J0Z Moderate Increased metabolism of S-297995 caused by Pexidartinib mediated induction of CYP450 enzyme. Bone/articular cartilage neoplasm [2F7B] [6]
HKI-272 DM6QOVN Moderate Decreased clearance of S-297995 due to the transporter inhibition by HKI-272. Breast cancer [2C60-2C6Y] [4]
PF-04449913 DMSB068 Moderate Decreased clearance of S-297995 due to the transporter inhibition by PF-04449913. Chronic myelomonocytic leukaemia [2A40] [4]
MK-8228 DMOB58Q Moderate Decreased clearance of S-297995 due to the transporter inhibition by MK-8228. Cytomegaloviral disease [1D82] [4]
Ingrezza DMVPLNC Moderate Decreased clearance of S-297995 due to the transporter inhibition by Ingrezza. Dystonic disorder [8A02] [4]
Berotralstat DMWA2DZ Moderate Decreased metabolism of S-297995 caused by Berotralstat mediated inhibition of CYP450 enzyme. Innate/adaptive immunodeficiency [4A00] [7]
PF-06463922 DMKM7EW Moderate Increased metabolism of S-297995 caused by PF-06463922 mediated induction of CYP450 enzyme. Lung cancer [2C25] [4]
Capmatinib DMYCXKL Moderate Decreased clearance of S-297995 due to the transporter inhibition by Capmatinib. Lung cancer [2C25] [8]
Selpercatinib DMZR15V Moderate Decreased metabolism of S-297995 caused by Selpercatinib mediated inhibition of CYP450 enzyme. Lung cancer [2C25] [4]
IPI-145 DMWA24P Moderate Decreased clearance of S-297995 due to the transporter inhibition by IPI-145. Mature B-cell leukaemia [2A82] [4]
Lasmiditan DMXLVDT Moderate Decreased clearance of S-297995 due to the transporter inhibition by Lasmiditan. Migraine [8A80] [9]
Fedratinib DM4ZBK6 Moderate Decreased metabolism of S-297995 caused by Fedratinib mediated inhibition of CYP450 enzyme. Myeloproliferative neoplasm [2A20] [4]
Rucaparib DM9PVX8 Moderate Decreased metabolism of S-297995 caused by Rucaparib mediated inhibition of CYP450 enzyme. Ovarian cancer [2C73] [10]
Abametapir DM2RX0I Moderate Decreased metabolism of S-297995 caused by Abametapir mediated inhibition of CYP450 enzyme. Pediculosis [1G00] [11]
Lefamulin DME6G97 Moderate Decreased metabolism of S-297995 caused by Lefamulin mediated inhibition of CYP450 enzyme. Pneumonia [CA40] [12]
Voxelotor DMCS6M5 Moderate Decreased clearance of S-297995 due to the transporter inhibition by Voxelotor. Sickle-cell disorder [3A51] [4]
Telotristat ethyl DMDIYFZ Moderate Increased metabolism of S-297995 caused by Telotristat ethyl mediated induction of CYP450 enzyme. Small intestine developmental anomaly [DA90] [4]
Larotrectinib DM26CQR Moderate Decreased metabolism of S-297995 caused by Larotrectinib mediated inhibition of CYP450 enzyme. Solid tumour/cancer [2A00-2F9Z] [3]
LEE011 DMMX75K Moderate Decreased metabolism of S-297995 caused by LEE011 mediated inhibition of CYP450 enzyme. Solid tumour/cancer [2A00-2F9Z] [4]
Fostamatinib DM6AUHV Moderate Decreased metabolism of S-297995 caused by Fostamatinib mediated inhibition of CYP450 enzyme. Thrombocytopenia [3B64] [13]
Elagolix DMB2C0E Moderate Decreased clearance of S-297995 due to the transporter inhibition by Elagolix. Uterine fibroid [2E86] [4]
⏷ Show the Full List of 25 DDI Information of This Drug

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

DIG
DIG Name DIG ID PubChem CID Functional Classification
Mannitol E00103 6251 Diluent; Flavoring agent; Lyophilization aid; Plasticizing agent; Tonicity agent
Carmellose sodium E00625 Not Available Disintegrant
Ferric hydroxide oxide yellow E00539 23320441 Colorant
Hypromellose E00634 Not Available Coating agent
Magnesium stearate E00208 11177 lubricant
Talc E00520 16211421 Anticaking agent; Diluent; Glidant; lubricant
⏷ Show the Full List of 6 Pharmaceutical Excipients of This Drug
Pharmaceutical Formulation
Formulation Name Drug Dosage Dosage Form Route
Naldemedine 0.2 mg tablet 0.2 mg Oral Tablet Oral
Naldemedine Tosylate 0.2mg tablet 0.2mg Tablet Oral
Jump to Detail Pharmaceutical Formulation Page of This Drug

References

1 Clinical pipeline report, company report or official report of Shionogi (2011).
2 Product Information. Symproic (naldemedine). Shionogi USA Inc, Florham Park, NJ.
3 Cerner Multum, Inc. "Australian Product Information.".
4 Cerner Multum, Inc. "UK Summary of Product Characteristics.".
5 Product Information. Balversa (erdafitinib). Janssen Products, LP, Horsham, PA.
6 Product Information. Turalio (pexidartinib). Daiichi Sankyo, Inc., Parsippany, NJ.
7 Product Information. Orladeyo (berotralstat). BioCryst Pharmaceuticals Inc, Durham, NC.
8 Product Information. Tabrecta (capmatinib). Novartis Pharmaceuticals, East Hanover, NJ.
9 Product Information. Reyvow (lasmiditan). Lilly, Eli and Company, Indianapolis, IN.
10 EMA. European Medicines Agency. European Union "EMA - List of medicines under additional monitoring.".
11 Product Information. Xeglyze (abametapir topical). Dr. Reddy's Laboratories Inc, Upper Saddle River, NJ.
12 Product Information. Xenleta (lefamulin). Nabriva Therapeutics US, Inc., King of Prussia, PA.
13 Product Information. Tavalisse (fostamatinib). Rigel Pharmaceuticals, South San Francisco, CA.