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]
ATC Code
L02BB06: Darolutamide
L02BB: Anti-androgens
L02B: HORMONE ANTAGONISTS AND RELATED AGENTS
L02: ENDOCRINE THERAPY
L: ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
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
ChEBI ID
CHEMBL4297185
CAS Number
1297538-32-9
UNII
X05U0N2RCO
DrugBank ID
DB12941
TTD ID
D0DV6D
INTEDE ID
DR0419
ACDINA ID
D00989
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Drug ADMET Endpoint Profile (DAE)NEW Click to Jump to the Detailed DAE Information of This Drug
Combinatorial Drugs (CBD) Click to Jump to the Detailed CBD Information of This Drug

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]

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]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

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) 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 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]
⏷ Show the Full List of 10 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
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
⏷ Show the Full List of 8 Pharmaceutical Excipients of This Drug
Pharmaceutical Formulation
Formulation Name Drug Dosage Dosage Form Route
Darolutamide 300 mg tablet 300 mg Tablet Oral
Jump to Detail Pharmaceutical Formulation Page of This Drug

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.".