Details of the Drug

General Information of Drug (ID: DMV7YFT)

Drug Name

Darolutamide

Synonyms

1297538-32-9; BAY-1841788; N-((S)-1-(3-(3-Chloro-4-cyanophenyl)-1H-pyrazol-1-yl)propan-2-yl)-5-(1-hydroxyethyl)-1H-pyrazole-3-carboxamide; Darolutamide [USAN]; Darolutamide (JAN/USAN/INN); SCHEMBL1814935; SCHEMBL13733117; KS-00000TSX; EX-A759; BLIJXOOIHRSQRB-PXYINDEMSA-N; MolPort-046-033-692; MolPort-044-560-277; AKOS030526387; CS-5174; BAY1841788; DB12941; BAY 1841788; HY-16985; S7559; FT-0700158; J3.501.129C; D11045; J-690121; 1H-Pyrazole-3-carboxamide, N-((1S)-2-(3-(3-chloro-4-cyanophen

Indication

Disease Entry	ICD 11	Status	REF
Prostate cancer	2C82.0	Approved	[1]
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Structure

3D MOL

2D MOL

#Ro5 Violations (Lipinski): 0

Molecular Weight (mw)

398.8

Logarithm of the Partition Coefficient (xlogp)

1.8

Rotatable Bond Count (rotbonds)

6

Hydrogen Bond Donor Count (hbonddonor)

3

Hydrogen Bond Acceptor Count (hbondacc)

5

ADMET Property

Absorption AUC: The area under the plot of plasma concentration (AUC) of drug is 52.82 mgh/L [2]
Absorption Cmax: The maximum plasma concentration (Cmax) of drug is 4.79 mg/L [2]
Absorption Tmax: The time to maximum plasma concentration (Tmax) is 3-6 h [2]
Clearance: The clearance of drug is 116 mL/min [2]
Elimination: In a pharmacokinetic study, a radiolabeled dose of darolutamide in an oral solution showed that 63.4% of darolutamide-related material was excreted in the urine (7% of which was unchanged drug) and 32.4% in the feces (with 30% unchanged drug) [2]
Half-life: The concentration or amount of drug in body reduced by one-half in 20 hours [2]
Metabolism: The drug is metabolized via the CYP3A4 hepatic microsomal enzyme in addition to UGT1A9 and UGT1A1 [3]
Vd: The volume of distribution (Vd) of drug is 119 L [2]

Chemical Identifiers

Formula: C19H19ClN6O2
IUPAC Name: N-[(2S)-1-[3-(3-chloro-4-cyanophenyl)pyrazol-1-yl]propan-2-yl]-5-(1-hydroxyethyl)-1H-pyrazole-3-carboxamide
Canonical SMILES: C[C@@H](CN1C=CC(=N1)C2=CC(=C(C=C2)C#N)Cl)NC(=O)C3=NNC(=C3)C(C)O
InChI: InChI=1S/C19H19ClN6O2/c1-11(22-19(28)18-8-17(12(2)27)23-24-18)10-26-6-5-16(25-26)13-3-4-14(9-21)15(20)7-13/h3-8,11-12,27H,10H2,1-2H3,(H,22,28)(H,23,24)/t11-,12?/m0/s1
InChIKey: BLIJXOOIHRSQRB-PXYINDEMSA-N

Cross-matching ID

PubChem CID: 67171867
CAS Number: 1297538-32-9
DrugBank ID: DB12941
TTD ID: D0DV6D
INTEDE ID: DR0419
ACDINA ID: D00989

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
Androgen receptor (AR)	TTS64P2	ANDR_HUMAN	Antagonist	[1]

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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]
UDP-glucuronosyltransferase 1A1 (UGT1A1)	DEYGVN4	UD11_HUMAN	Substrate	[4]
UDP-glucuronosyltransferase 1A9 (UGT1A9)	DE85D2P	UD19_HUMAN	Substrate	[4]
UDP-glucuronosyltransferase 1A3 (UGT1A3)	DEF2WXN	UD13_HUMAN	Substrate	[4]
UDP-glucuronosyltransferase 1A8 (UGT1A8)	DE2GB8N	UD18_HUMAN	Substrate	[4]
UDP-glucuronosyltransferase 2B17 (UGT2B17)	DEAZDL8	UDB17_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

Prostate cancer

ICD Disease Classification

2C82.0

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Androgen receptor (AR)	DTT	AR	2.13E-01	-0.07	-0.11
UDP-glucuronosyltransferase 1A1 (UGT1A1)	DME	UGT1A1	6.96E-03	-1.95E-01	-8.72E-01
UDP-glucuronosyltransferase 2B17 (UGT2B17)	DME	UGT2B17	7.62E-01	1.33E-02	9.61E-02
Cytochrome P450 3A4 (CYP3A4)	DME	CYP3A4	7.93E-02	-8.20E-02	-8.93E-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 Darolutamide (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Ivosidenib	DM8S6T7	Moderate	Increased metabolism of Darolutamide caused by Ivosidenib mediated induction of CYP450 enzyme.	Acute myeloid leukaemia [2A60]	[5]
Troleandomycin	DMUZNIG	Minor	Decreased metabolism of Darolutamide caused by Troleandomycin mediated inhibition of CYP450 enzyme.	Bacterial infection [1A00-1C4Z]	[5]
Pexidartinib	DMS2J0Z	Moderate	Increased metabolism of Darolutamide caused by Pexidartinib mediated induction of CYP450 enzyme.	Bone/articular cartilage neoplasm [2F7B]	[5]
Eslicarbazepine	DMZREFQ	Moderate	Increased metabolism of Darolutamide caused by Eslicarbazepine mediated induction of CYP450 enzyme.	Epilepsy/seizure [8A61-8A6Z]	[5]
Berotralstat	DMWA2DZ	Major	Decreased clearance of Darolutamide due to the transporter inhibition by Berotralstat.	Innate/adaptive immunodeficiency [4A00]	[6]
Selpercatinib	DMZR15V	Minor	Decreased metabolism of Darolutamide caused by Selpercatinib mediated inhibition of CYP450 enzyme.	Lung cancer [2C25]	[5]
Ubrogepant	DM749I3	Moderate	Decreased clearance of Darolutamide due to the transporter inhibition by Ubrogepant.	Migraine [8A80]	[7]
Voxelotor	DMCS6M5	Minor	Decreased clearance of Darolutamide due to the transporter inhibition by Voxelotor.	Sickle-cell disorder [3A51]	[5]
Larotrectinib	DM26CQR	Minor	Decreased metabolism of Darolutamide caused by Larotrectinib mediated inhibition of CYP450 enzyme.	Solid tumour/cancer [2A00-2F9Z]	[5]
Lusutrombopag	DMH6IKO	Moderate	Decreased clearance of Darolutamide due to the transporter inhibition by Lusutrombopag.	Thrombocytopenia [3B64]	[8]
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Drug Inactive Ingredient(s) (DIG) and Formulation(s) of This Drug

DIG

DIG Name	DIG ID	PubChem CID	Functional Classification
Calcium hydrogenphosphate	E00294	24441	Diluent
Carmellose sodium	E00625	Not Available	Disintegrant
Hypromellose	E00634	Not Available	Coating agent
Lactose monohydrate	E00393	104938	Binding agent; Diluent; Dry powder inhaler carrier; Lyophilization aid
Magnesium stearate	E00208	11177	lubricant
Polyethylene glycol 3350	E00652	Not Available	Coating agent; Diluent; Ointment base; Plasticizing agent; Solvent; Suppository base; lubricant
Povidone	E00667	Not Available	Binding agent; Coating agent; Disintegrant; Film/membrane-forming agent; Solubilizing agent; Suspending agent
Titanium dioxide	E00322	26042	Coating agent; Colorant; Opacifying agent
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Pharmaceutical Formulation

Formulation Name	Drug Dosage	Dosage Form	Route
Darolutamide 300 mg tablet	300 mg	Tablet	Oral

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References

1	Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2019
2	FDA Approved Drug Products: NUBEQA (darolutamide) tablets, for oral use
3	Murayama N, Imai N, Nakane T, Shimizu M, Yamazaki H: Roles of CYP3A4 and CYP2C19 in methyl hydroxylated and N-oxidized metabolite formation from voriconazole, a new anti-fungal agent, in human liver microsomes. Biochem Pharmacol. 2007 Jun 15;73(12):2020-6. doi: 10.1016/j.bcp.2007.03.012. Epub 2007 Mar 19.
4	Drug-drug interaction potential of darolutamide: in vitro and clinical studies. Eur J Drug Metab Pharmacokinet. 2019 Dec;44(6):747-759.
5	Product Information. Nubeqa (darolutamide). Bayer HealthCare Pharmaceuticals Inc., Whippany, NJ.
6	Product Information. Orladeyo (berotralstat). BioCryst Pharmaceuticals Inc, Durham, NC.
7	Product Information. Ubrelvy (ubrogepant). Allergan Inc, Irvine, CA.
8	EMA. European Medicines Agency. European Union "EMA - List of medicines under additional monitoring.".