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

Topological Polar Surface Area (xlogp)

3.2

Rotatable Bond Count (rotbonds)

Hydrogen Bond Donor Count (hbonddonor)

Hydrogen Bond Acceptor Count (hbondacc)

ADMET Property

Absorption Tmax: The time to maximum plasma concentration (Tmax) is 0.75 h [2]
Elimination: 57% of naldemedine is excreted in the urine with 16-18% as the parent compound and 35% is excreted in the feces [3]
Half-life: The concentration or amount of drug in body reduced by one-half in 11 hours [2]
Metabolism: The drug is metabolized via the CYP3A [2]
Vd: The volume of distribution (Vd) of drug is 155 L [3]

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)

MIA Detail

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]	[14]
Gilteritinib	DMWQ4MZ	Moderate	Decreased clearance of S-297995 due to the transporter inhibition by Gilteritinib.	Acute myeloid leukaemia [2A60]	[15]
Troleandomycin	DMUZNIG	Moderate	Decreased metabolism of S-297995 caused by Troleandomycin mediated inhibition of CYP450 enzyme.	Bacterial infection [1A00-1C4Z]	[16]
Erdafitinib	DMI782S	Moderate	Decreased clearance of S-297995 due to the transporter inhibition by Erdafitinib.	Bladder cancer [2C94]	[17]
Pexidartinib	DMS2J0Z	Moderate	Increased metabolism of S-297995 caused by Pexidartinib mediated induction of CYP450 enzyme.	Bone/articular cartilage neoplasm [2F7B]	[18]
HKI-272	DM6QOVN	Moderate	Decreased clearance of S-297995 due to the transporter inhibition by HKI-272.	Breast cancer [2C60-2C6Y]	[16]
PF-04449913	DMSB068	Moderate	Decreased clearance of S-297995 due to the transporter inhibition by PF-04449913.	Chronic myelomonocytic leukaemia [2A40]	[16]
MK-8228	DMOB58Q	Moderate	Decreased clearance of S-297995 due to the transporter inhibition by MK-8228.	Cytomegaloviral disease [1D82]	[16]
Ingrezza	DMVPLNC	Moderate	Decreased clearance of S-297995 due to the transporter inhibition by Ingrezza.	Dystonic disorder [8A02]	[16]
Berotralstat	DMWA2DZ	Moderate	Decreased metabolism of S-297995 caused by Berotralstat mediated inhibition of CYP450 enzyme.	Innate/adaptive immunodeficiency [4A00]	[19]
PF-06463922	DMKM7EW	Moderate	Increased metabolism of S-297995 caused by PF-06463922 mediated induction of CYP450 enzyme.	Lung cancer [2C25]	[16]
Capmatinib	DMYCXKL	Moderate	Decreased clearance of S-297995 due to the transporter inhibition by Capmatinib.	Lung cancer [2C25]	[20]
Selpercatinib	DMZR15V	Moderate	Decreased metabolism of S-297995 caused by Selpercatinib mediated inhibition of CYP450 enzyme.	Lung cancer [2C25]	[16]
IPI-145	DMWA24P	Moderate	Decreased clearance of S-297995 due to the transporter inhibition by IPI-145.	Mature B-cell leukaemia [2A82]	[16]
Lasmiditan	DMXLVDT	Moderate	Decreased clearance of S-297995 due to the transporter inhibition by Lasmiditan.	Migraine [8A80]	[21]
Fedratinib	DM4ZBK6	Moderate	Decreased metabolism of S-297995 caused by Fedratinib mediated inhibition of CYP450 enzyme.	Myeloproliferative neoplasm [2A20]	[16]
Rucaparib	DM9PVX8	Moderate	Decreased metabolism of S-297995 caused by Rucaparib mediated inhibition of CYP450 enzyme.	Ovarian cancer [2C73]	[22]
Abametapir	DM2RX0I	Moderate	Decreased metabolism of S-297995 caused by Abametapir mediated inhibition of CYP450 enzyme.	Pediculosis [1G00]	[23]
Lefamulin	DME6G97	Moderate	Decreased metabolism of S-297995 caused by Lefamulin mediated inhibition of CYP450 enzyme.	Pneumonia [CA40]	[24]
Voxelotor	DMCS6M5	Moderate	Decreased clearance of S-297995 due to the transporter inhibition by Voxelotor.	Sickle-cell disorder [3A51]	[16]
Telotristat ethyl	DMDIYFZ	Moderate	Increased metabolism of S-297995 caused by Telotristat ethyl mediated induction of CYP450 enzyme.	Small intestine developmental anomaly [DA90]	[16]
Larotrectinib	DM26CQR	Moderate	Decreased metabolism of S-297995 caused by Larotrectinib mediated inhibition of CYP450 enzyme.	Solid tumour/cancer [2A00-2F9Z]	[15]
LEE011	DMMX75K	Moderate	Decreased metabolism of S-297995 caused by LEE011 mediated inhibition of CYP450 enzyme.	Solid tumour/cancer [2A00-2F9Z]	[16]
Fostamatinib	DM6AUHV	Moderate	Decreased metabolism of S-297995 caused by Fostamatinib mediated inhibition of CYP450 enzyme.	Thrombocytopenia [3B64]	[25]
Elagolix	DMB2C0E	Moderate	Decreased clearance of S-297995 due to the transporter inhibition by Elagolix.	Uterine fibroid [2E86]	[16]
-----------


⏷ 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	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.
3	An FDA phase I clinical trial of quinacrine sterilization (QS). Int J Gynaecol Obstet. 2003 Oct;83 Suppl 2:S45-9.
4	Methadone treatment and its dangers. Medicina (Kaunas). 2009;45(5):419-25.
5	The mu1 and mu2 opioid receptor binding of ketobemidone, norketobemidone and 3-dimethylamino-1,1-diphenylbutene. Pharmacol Toxicol. 1996 Aug;79(2):103-4.
6	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: 7094).
7	Retrospective diagnosis of an adverse drug reaction in a breastfed neonate: liquid chromatography-tandem mass spectrometry quantification of dextropropoxyphene and norpropoxyphene in newborn and maternal hair. J Anal Toxicol. 2008 Nov-Dec;39(9):787-9.
8	mu-opioid receptor-stimulated synthesis of reactive oxygen species is mediated via phospholipase D2. J Neurochem. 2009 Aug;110(4):1288-96.
9	An evaluation of mu-opioid receptor (OPRM1) as a predictor of naltrexone response in the treatment of alcohol dependence: results from the Combined Pharmacotherapies and Behavioral Interventions for Alcohol Dependence (COMBINE) study. Arch Gen Psychiatry. 2008 Feb;65(2):135-44.
10	Comparison of the effects of dextromethorphan, dextrorphan, and levorphanol on the hypothalamo-pituitary-adrenal axis. J Pharmacol Exp Ther. 2004 May;309(2):515-22.
11	Functional characterization of a sigma receptor and its gene expression by haloperidol. Nippon Yakurigaku Zasshi. 1999 Jul;114(1):61-8.
12	Unconditioned behavioral effects of the powerful kappa-opioid hallucinogen salvinorin A in nonhuman primates: fast onset and entry into cerebrospin... J Pharmacol Exp Ther. 2009 Feb;328(2):588-97.
13	Actions of tilidine and nortilidine on cloned opioid receptors. Eur J Pharmacol. 2005 Jan 4;506(3):205-8.
14	Product Information. Symproic (naldemedine). Shionogi USA Inc, Florham Park, NJ.
15	Cerner Multum, Inc. "Australian Product Information.".
16	Cerner Multum, Inc. "UK Summary of Product Characteristics.".
17	Product Information. Balversa (erdafitinib). Janssen Products, LP, Horsham, PA.
18	Product Information. Turalio (pexidartinib). Daiichi Sankyo, Inc., Parsippany, NJ.
19	Product Information. Orladeyo (berotralstat). BioCryst Pharmaceuticals Inc, Durham, NC.
20	Product Information. Tabrecta (capmatinib). Novartis Pharmaceuticals, East Hanover, NJ.
21	Product Information. Reyvow (lasmiditan). Lilly, Eli and Company, Indianapolis, IN.
22	EMA. European Medicines Agency. European Union "EMA - List of medicines under additional monitoring.".
23	Product Information. Xeglyze (abametapir topical). Dr. Reddy's Laboratories Inc, Upper Saddle River, NJ.
24	Product Information. Xenleta (lefamulin). Nabriva Therapeutics US, Inc., King of Prussia, PA.
25	Product Information. Tavalisse (fostamatinib). Rigel Pharmaceuticals, South San Francisco, CA.