Details of the Drug

General Information of Drug (ID: DM8XP26)

Drug Name

Rolapitant

Synonyms

Rolapitant; 552292-08-7; Sch 619734; Varubi; UNII-NLE429IZUC; SCH-619734; NLE429IZUC; 914462-92-3; (5S,8S)-8-(((R)-1-(3,5-bis(trifluoromethyl)phenyl)ethoxy)methyl)-8-phenyl-1,7-diazaspiro[4.5]decan-2-one; (5S,8S)-8-[[(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethoxy]methyl]-8-phenyl-1,9-diazaspiro[4.5]decan-2-one; Rolapitant [USAN:INN]; Varuby; Varubi (TN); Rolapitant (USAN/INN); Rolapitant(sch619734); SCHEMBL354305; GTPL5749; CHEMBL3707331; CHEBI:90908; DTXSID90203740; MolPort-035-942-975; EX-A1288; BCP09609; ZINC3816514

Indication

Disease Entry	ICD 11	Status	REF
Chemotherapy-induced nausea	MD90	Approved	[1]
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Drug Type

Small molecular drug

Structure

3D MOL is unavailable

2D MOL

#Ro5 Violations (Lipinski): 1

Molecular Weight (mw)

500.5

Logarithm of the Partition Coefficient (xlogp)

4.4

Rotatable Bond Count (rotbonds)

Hydrogen Bond Donor Count (hbonddonor)

Hydrogen Bond Acceptor Count (hbondacc)

ADMET Property

Clearance: The clearance of drug is 0.96 L/h []
Half-life: The concentration or amount of drug in body reduced by one-half in 169 - 183 hours [2]
Metabolism: The drug is metabolized via the cytochrome P450 enzyme 3A4 (CYP3A4) to its major active and circulating metabolite M19 (C4-pyrrolidine-hydroxylated rolapitant) []
Unbound Fraction: The unbound fraction of drug in plasma is 0.002% [2]
Vd: The volume of distribution (Vd) of drug is 460 L []

Chemical Identifiers

Formula: C25H26F6N2O2
IUPAC Name: (5S,8S)-8-[[(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethoxy]methyl]-8-phenyl-1,9-diazaspiro[4.5]decan-2-one
Canonical SMILES: C[C@H](C1=CC(=CC(=C1)C(F)(F)F)C(F)(F)F)OC[C@]2(CC[C@]3(CCC(=O)N3)CN2)C4=CC=CC=C4
InChI: InChI=1S/C25H26F6N2O2/c1-16(17-11-19(24(26,27)28)13-20(12-17)25(29,30)31)35-15-23(18-5-3-2-4-6-18)10-9-22(14-32-23)8-7-21(34)33-22/h2-6,11-13,16,32H,7-10,14-15H2,1H3,(H,33,34)/t16-,22-,23-/m1/s1
InChIKey: FIVSJYGQAIEMOC-ZGNKEGEESA-N

Cross-matching ID

PubChem CID: 10311306
ChEBI ID: CHEBI:90908
CAS Number: 552292-08-7
DrugBank ID: DB09291
TTD ID: D0CF0Y
INTEDE ID: DR1437
ACDINA ID: D00605

Combinatorial Drugs (CBD)

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Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Substance-P receptor (TACR1)	TTZPO1L	NK1R_HUMAN	Antagonist	[3]

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Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 3A4 (CYP3A4)_{Main DME}	DE4LYSA	CP3A4_HUMAN	Substrate	[4]

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Molecular Interaction Atlas (MIA)

MIA Detail

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Molecular Expression Atlas of This Drug

The Studied Disease

Chemotherapy-induced nausea

ICD Disease Classification

MD90

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Substance-P receptor (TACR1)	DTT	TACR1	7.40E-01	0.02	0.07
Substance-P receptor (TACR1)	DTT	TACR1	8.57E-01	-0.02	-0.18
Cytochrome P450 3A4 (CYP3A4)	DME	CYP3A4	4.66E-01	4.25E-02	1.20E-01
Cytochrome P450 3A4 (CYP3A4)	DME	CYP3A4	4.75E-01	5.15E-02	3.64E-01

Molecular Expression Atlas (MEA)

MEA Detail

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Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Rolapitant (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Ivosidenib	DM8S6T7	Moderate	Increased metabolism of Rolapitant caused by Ivosidenib mediated induction of CYP450 enzyme.	Acute myeloid leukaemia [2A60]	[5]
Arn-509	DMT81LZ	Major	Increased metabolism of Rolapitant caused by Arn-509 mediated induction of CYP450 enzyme.	Acute myeloid leukaemia [2A60]	[6]
Gilteritinib	DMTI0ZO	Moderate	Decreased clearance of Rolapitant due to the transporter inhibition by Gilteritinib.	Acute myeloid leukaemia [2A60]	[5]
Oliceridine	DM6MDCF	Major	Decreased metabolism of Rolapitant caused by Oliceridine mediated inhibition of CYP450 enzyme.	Acute pain [MG31]	[7]
Pexidartinib	DMS2J0Z	Moderate	Increased metabolism of Rolapitant caused by Pexidartinib mediated induction of CYP450 enzyme.	Bone/articular cartilage neoplasm [2F7B]	[5]
Talazoparib	DM1KS78	Moderate	Decreased clearance of Rolapitant due to the transporter inhibition by Talazoparib.	Breast cancer [2C60-2C6Y]	[5]
Eslicarbazepine	DMZREFQ	Moderate	Increased metabolism of Rolapitant caused by Eslicarbazepine mediated induction of CYP450 enzyme.	Epilepsy/seizure [8A61-8A6Z]	[6]
Tazemetostat	DMWP1BH	Moderate	Increased metabolism of Rolapitant caused by Tazemetostat mediated induction of CYP450 enzyme.	Follicular lymphoma [2A80]	[5]
Ripretinib	DM958QB	Moderate	Decreased clearance of Rolapitant due to the transporter inhibition by Ripretinib.	Gastrointestinal stromal tumour [2B5B]	[5]
Berotralstat	DMWA2DZ	Major	Decreased clearance of Rolapitant due to the transporter inhibition by Berotralstat.	Innate/adaptive immunodeficiency [4A00]	[8]
PF-06463922	DMKM7EW	Moderate	Increased metabolism of Rolapitant caused by PF-06463922 mediated induction of CYP450 enzyme.	Lung cancer [2C25]	[5]
GDC-0199	DMH0QKA	Major	Decreased clearance of Rolapitant due to the transporter inhibition by GDC-0199.	Mature B-cell leukaemia [2A82]	[9]
Arry-162	DM1P6FR	Moderate	Decreased clearance of Rolapitant due to the transporter inhibition by Arry-162.	Melanoma [2C30]	[5]
Ubrogepant	DM749I3	Moderate	Decreased clearance of Rolapitant due to the transporter inhibition by Ubrogepant.	Migraine [8A80]	[10]
Rimegepant	DMHOAUG	Moderate	Decreased clearance of Rolapitant due to the transporter inhibition by Rimegepant.	Migraine [8A80]	[11]
S-297995	DM26IH8	Moderate	Decreased clearance of Rolapitant due to the transporter inhibition by S-297995.	Opioid use disorder [6C43]	[5]
MK-4827	DMLYGH4	Moderate	Decreased clearance of Rolapitant due to the transporter inhibition by MK-4827.	Ovarian cancer [2C73]	[5]
Abametapir	DM2RX0I	Moderate	Decreased metabolism of Rolapitant caused by Abametapir mediated inhibition of CYP450 enzyme.	Pediculosis [1G00]	[12]
Lefamulin	DME6G97	Moderate	Decreased metabolism of Rolapitant caused by Lefamulin mediated inhibition of CYP450 enzyme.	Pneumonia [CA40]	[13]
Relugolix	DMK7IWL	Major	Decreased clearance of Rolapitant due to the transporter inhibition by Relugolix.	Prostate cancer [2C82]	[14]
Telotristat ethyl	DMDIYFZ	Moderate	Increased metabolism of Rolapitant caused by Telotristat ethyl mediated induction of CYP450 enzyme.	Small intestine developmental anomaly [DA90]	[6]
Larotrectinib	DM26CQR	Moderate	Decreased clearance of Rolapitant due to the transporter inhibition by Larotrectinib.	Solid tumour/cancer [2A00-2F9Z]	[5]
Pitolisant	DM8RFNJ	Moderate	Decreased metabolism of Rolapitant caused by Pitolisant mediated inhibition of CYP450 enzyme.	Somnolence [MG42]	[6]
Fostamatinib	DM6AUHV	Moderate	Decreased metabolism of Rolapitant caused by Fostamatinib mediated inhibition of CYP450 enzyme.	Thrombocytopenia [3B64]	[15]
Lusutrombopag	DMH6IKO	Moderate	Decreased clearance of Rolapitant due to the transporter inhibition by Lusutrombopag.	Thrombocytopenia [3B64]	[5]
Elagolix	DMB2C0E	Moderate	Increased metabolism of Rolapitant caused by Elagolix mediated induction of CYP450 enzyme.	Uterine fibroid [2E86]	[5]
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Drug Inactive Ingredient(s) (DIG) and Formulation(s) of This Drug

DIG

DIG Name	DIG ID	PubChem CID	Functional Classification
FD&C blue no. 2	E00446	2723854	Colorant
Carmellose sodium	E00625	Not Available	Disintegrant
Disodium hydrogenorthophosphate	E00283	24203	Buffering agent; Complexing agent
Lactose monohydrate	E00393	104938	Binding agent; Diluent; Dry powder inhaler carrier; Lyophilization aid
Magnesium stearate	E00208	11177	lubricant
Medium-chain triglyceride	E00640	Not Available	Emollient; Lubricant; Surfactant
Polyethylene glycol 4000	E00654	Not Available	Coating agent; Diluent; Ointment base; Plasticizing agent; Solvent; Suppository base; lubricant
Polysorbate 80	E00665	Not Available	Dispersing agent; Emollient; Emulsifying agent; Plasticizing agent; Solubilizing agent; Surfactant; Suspending agent
Polyvinyl alcohol	E00666	Not Available	Coating agent; Emulsion stabilizing agent; Film/Membrane-forming agent
Povidone	E00667	Not Available	Binding agent; Coating agent; Disintegrant; Film/membrane-forming agent; Solubilizing agent; Suspending agent
Silicon dioxide	E00670	Not Available	Anticaking agent; Opacifying agent; Viscosity-controlling agent
Sodium chloride	E00077	5234	Diluent; Tonicity agent
Talc	E00520	16211421	Anticaking agent; Diluent; Glidant; lubricant
Titanium dioxide	E00322	26042	Coating agent; Colorant; Opacifying agent
Water	E00035	962	Solvent
Hydrophobic colloidal silica	E00285	24261	Anticaking agent; Emulsion stabilizing agent; Glidant; Suspending agent; Viscosity-controlling agent
Cellulose microcrystalline	E00698	Not Available	Adsorbent; Suspending agent; Diluent
Glyceryl monolinoleate	E00639	Not Available	Other agent
Polyoxyl 15 hydroxystearate	E00659	Not Available	Emulsifying agent; Solubilizing agent; Surfactant
Pregelatinized starch	E00674	Not Available	Binding agent; Diluent; Disintegrant
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Pharmaceutical Formulation

Formulation Name	Drug Dosage	Dosage Form	Route
Rolapitant Hydrochloride eq 90mg base tablet	eq 90mg base	Tablet	Oral
Rolapitant 90 mg tablet	90 mg	Oral Tablet	Oral
Rolapitant Hydrochloride eq 166.5mg base/92.5ml Emulsion	eq 166.5mg base/92.5ml	Emulsion	Intravenous

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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: 5749).
2	Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
3	Netupitant and palonosetron trigger NK1 receptor internalization in NG108-15 cells. Exp Brain Res. 2014 Aug;232(8):2637-44.
4	Pharmacokinetic interactions of rolapitant with cytochrome P450 3A substrates in healthy subjects. J Clin Pharmacol. 2019 Apr;59(4):488-499.
5	Product Information. Varubi (rolapitant). Tesaro Inc., Waltham, MA.
6	Cerner Multum, Inc. "UK Summary of Product Characteristics.".
7	Product Information. Olinvyk (oliceridine). Trevena Inc, Chesterbrook, PA.
8	Product Information. Orladeyo (berotralstat). BioCryst Pharmaceuticals Inc, Durham, NC.
9	Cerner Multum, Inc. "Australian Product Information.".
10	Product Information. Ubrelvy (ubrogepant). Allergan Inc, Irvine, CA.
11	Product Information. Nurtec ODT (rimegepant). Biohaven Pharmaceuticals, New Haven, CT.
12	Product Information. Xeglyze (abametapir topical). Dr. Reddy's Laboratories Inc, Upper Saddle River, NJ.
13	Product Information. Fycompa (perampanel). Eisai Inc, Teaneck, NJ.
14	Product Information. Orgovyx (relugolix). Myovant Sciences, Inc., Brisbane, CA.
15	Product Information. Tavalisse (fostamatinib). Rigel Pharmaceuticals, South San Francisco, CA.