darolutamide 🐶 Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | PK/Tox | Related Drugs | BioActivity |

Stem definitionDrug idCAS RN
non-steroid antiandrogens 5334 1297538-32-9

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • darolutamide
  • nubeqa
  • BAY 1841788
  • ODM-201
Darolutamide is an androgen receptor (AR) inhibitor. Darolutamide competitively inhibits androgen binding, AR nuclear translocation, and AR-mediated transcription. A major metabolite, keto-darolutamide, exhibited similar in vitro activity to darolutamide. In addition, darolutamide functioned as a progesterone receptor (PR) antagonist in vitro (approximately 1% activity compared to AR). Darolutamide decreased prostate cancer cell proliferation in vitro and tumor volume in mouse xenograft models of prostate cancer
  • Molecular weight: 398.85
  • Formula: C19H19ClN6O2
  • CLOGP: 1.98
  • LIPINSKI: 0
  • HAC: 8
  • HDO: 3
  • TPSA: 119.62
  • ALOGS: -3.74
  • ROTB: 6
  • Status: ONP
    • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

DoseUnitRoute
1.20 g O

ADMET properties:

PropertyValueReference
S (Water solubility) 0.01 mg/mL Bocci G, Oprea TI, Benet LZ
BDDCS (Biopharmaceutical Drug Disposition Classification System) 2 Bocci G, Oprea TI, Benet LZ

Predicted pharmacokinetic/toxicological properties (PK-AZ):

PropertyDescriptionValueUnitConfidenceSimilarity
azlogd74 LogD at pH 7.4 2.567 High 0.81
caco2-efflux Caco-2 efflux ratio (BA/AB) 42.462 High 0.81
caco2-intrinsic-papp Caco-2 intrinsic apparent permeability 20.797 10^-6 cm/s High 0.81
dh-clint Dog hepatocyte intrinsic clearance 2.270 uL/min/10^6 cells High 0.81
dppb Dog plasma protein binding (% unbound) 11.910 % High 0.81
fcs-ppb Fetal calf serum protein binding (% unbound) 27.500 % High 0.81
herg hERG pIC50 4.633 pIC50 High 0.81
hh-clint Human hepatocyte intrinsic clearance 1.469 uL/min/10^6 cells High 0.81
hlm-clint Human liver microsomal intrinsic clearance 9.683 uL/min/mg protein High 0.81
hppb Human plasma protein binding (% unbound) 11.620 % High 0.81
kinase-safety-class ACVR2B,AXL,CAMK2D,CDK9,EIF2AK3,GRK2,PDK1,PDK2,PDK4,PRKDC 10
mdck-mdr1-efflux MDCK-MDR1 efflux ratio 29.107 High 0.81
mh-clint Mouse hepatocyte intrinsic clearance 16.293 High 0.81
mppb Mouse plasma protein binding (% unbound) 12.500 High 0.81
nih-mdck-mdr1-efflux NIH MDCK-MDR1 efflux ratio 36.983 High 0.81
pfas-class PFAS structural alert (1 = True, 0 = False) 0
pppb Pig plasma protein binding (% unbound) 21.360 % High 0.81
rh-clint Rat hepatocyte intrinsic clearance 8.241 uL/min/10^6 cells High 0.81
rh-fuinc Rat hepatocyte fraction unbound in incubation 66.100 % High 0.81
rppb Rat plasma protein binding (% unbound) 9.070 % High 0.81
solubility-dd Solubility at pH 7.4 in DMSO 226.986 uM High 0.81

Approvals:

DateAgencyCompanyOrphan
Jan. 23, 2020 PMDA Bayer Yakuhin, Ltd
March 27, 2020 EMA Bayer AG
July 30, 2019 FDA BAYER HEALTHCARE PHARMACEUTICALS INC

FDA Adverse Event Reporting System (Female)

None

FDA Adverse Event Reporting System (Male)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Prostatic specific antigen increased 384.07 24.74 117 4066 16808 42600344
Metastases to bone 242.85 24.74 80 4103 14729 42602423
Hormone-refractory prostate cancer 102.58 24.74 23 4160 981 42616171
Hot flush 102.56 24.74 48 4135 22303 42594849
Interstitial lung disease 86.07 24.74 67 4116 78395 42538757
Neuropathy peripheral 84.63 24.74 74 4109 101779 42515373
Neutrophil count decreased 82.53 24.74 60 4123 63355 42553797
Myelosuppression 68.42 24.74 45 4138 40416 42576736
Fatigue 54.88 24.74 127 4056 435514 42181638
Death 50.42 24.74 129 4054 471056 42146096
Metastases to lymph nodes 47.64 24.74 19 4164 5979 42611173
Alopecia 41.00 24.74 29 4154 29247 42587905
Vasogenic cerebral oedema 40.64 24.74 11 4172 1025 42616127
Prostate cancer 36.10 24.74 32 4151 44611 42572541
Prostatic specific antigen abnormal 32.48 24.74 9 4174 915 42616237
Arnold-Chiari malformation 29.54 24.74 7 4176 381 42616771
Malignant neoplasm progression 29.24 24.74 44 4139 108356 42508796
Pneumonitis 26.21 24.74 26 4157 41692 42575460
Liver function test increased 26.13 24.74 19 4164 19979 42597173
Metastases to spine 25.31 24.74 10 4173 3067 42614085

FDA Adverse Event Reporting System (Geriatric)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Prostatic specific antigen increased 355.48 29.04 80 3031 12431 110573757
Metastases to bone 203.12 29.04 62 3049 31310 110554878
Neutrophil count decreased 90.85 29.04 51 3060 120890 110465298
Neuropathy peripheral 79.46 29.04 54 3057 179223 110406965
Hot flush 78.76 29.04 38 3073 65998 110520190
Hormone-refractory prostate cancer 74.32 29.04 14 3097 896 110585292
Death 68.93 29.04 91 3020 698778 109887410
Interstitial lung disease 66.58 29.04 44 3067 139290 110446898
Prostate cancer 48.94 29.04 23 3088 37618 110548570
Vasogenic cerebral oedema 45.78 29.04 11 3100 2247 110583941
Metastases to lymph nodes 42.60 29.04 16 3095 15016 110571172
Arnold-Chiari malformation 40.82 29.04 7 3104 262 110585926
Prostatic specific antigen abnormal 40.33 29.04 8 3103 671 110585517
Febrile neutropenia 40.30 29.04 47 3064 316720 110269468
Myelosuppression 38.38 29.04 27 3084 94313 110491875
Fatigue 36.85 29.04 95 3016 1215863 109370325
Pneumonitis 33.70 29.04 23 3088 76508 110509680

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

SourceCodeDescription
ATC L02BB06 ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
ENDOCRINE THERAPY
HORMONE ANTAGONISTS AND RELATED AGENTS
Anti-androgens
CHEBI has role CHEBI:35497 androgen antagonist
CHEBI has role CHEBI:35610 antineoplastic agent
CHEBI has role CHEBI:50905 teratogenic agent

Related Drugs by ATC class:

L02BB Anti-androgens 5 drugs
apalutamidebicalutamideenzalutamideflutamidenilutamide

Drug Use | Suggest Off label Use Form| |View source of the data|

DiseaseRelationSNOMED_IDDOID
Metastatic prostate cancer indication 94503003
Hormone refractory prostate cancer indication 427492003




🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 11.99 acidic
pKa2 12.59 acidic
pKa3 1.18 Basic

Orange Book patent data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRoutePatent numberPatent expiration datePatent use
300MG NUBEQA BAYER HEALTHCARE N212099 July 30, 2019 RX TABLET ORAL 9657003 Oct. 27, 2030 TREATMENT OF ADULT PATIENTS WITH METASTATIC CASTRATION-SENSITIVE PROSTATE CANCER (MCSPC)
300MG NUBEQA BAYER HEALTHCARE N212099 July 30, 2019 RX TABLET ORAL 9657003 Oct. 27, 2030 TREATMENT OF ADULT PATIENTS WITH METASTATIC CASTRATION-SENSITIVE PROSTATE CANCER (MCSPC) IN COMBINATION WITH DOCETAXEL
300MG NUBEQA BAYER HEALTHCARE N212099 July 30, 2019 RX TABLET ORAL 9657003 Oct. 27, 2030 TREATMENT OF ADULT PATIENTS WITH NON-METASTATIC CASTRATION RESISTANT PROSTATE CANCER (NMCRPC)
300MG NUBEQA BAYER HEALTHCARE N212099 July 30, 2019 RX TABLET ORAL 8975254 March 25, 2033 TREATMENT OF ADULT PATIENTS WITH METASTATIC CASTRATION-SENSITIVE PROSTATE CANCER (MCSPC)
300MG NUBEQA BAYER HEALTHCARE N212099 July 30, 2019 RX TABLET ORAL 8975254 March 25, 2033 TREATMENT OF ADULT PATIENTS WITH METASTATIC CASTRATION-SENSITIVE PROSTATE CANCER (MCSPC) IN COMBINATION WITH DOCETAXEL
300MG NUBEQA BAYER HEALTHCARE N212099 July 30, 2019 RX TABLET ORAL 8975254 March 25, 2033 TREATMENT OF ADULT PATIENTS WITH NON-METASTATIC CASTRATION RESISTANT PROSTATE CANCER (NMCRPC)
300MG NUBEQA BAYER HEALTHCARE N212099 July 30, 2019 RX TABLET ORAL 10835515 Jan. 28, 2036 TREATMENT OF ADULT PATIENTS WITH METASTATIC CASTRATION-SENSITIVE PROSTATE CANCER (MCSPC)
300MG NUBEQA BAYER HEALTHCARE N212099 July 30, 2019 RX TABLET ORAL 10835515 Jan. 28, 2036 TREATMENT OF ADULT PATIENTS WITH METASTATIC CASTRATION-SENSITIVE PROSTATE CANCER (MCSPC) IN COMBINATION WITH DOCETAXEL
300MG NUBEQA BAYER HEALTHCARE N212099 July 30, 2019 RX TABLET ORAL 10835515 Jan. 28, 2036 TREATMENT OF ADULT PATIENTS WITH NON-METASTATIC CASTRATION RESISTANT PROSTATE CANCER (NMCRPC)
300MG NUBEQA BAYER HEALTHCARE N212099 July 30, 2019 RX TABLET ORAL 10835515 Jan. 28, 2036 TREATMENT OF PATIENTS WITH NON-METASTATIC CASTRATION RESISTANT PROSTATE CANCER

Orange Book exclusivity data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRouteExclusivity dateDescription
300MG NUBEQA BAYER HEALTHCARE N212099 July 30, 2019 RX TABLET ORAL June 3, 2028 DAROLUTAMIDE AS A SINGLE AGENT FOR TREATMENT OF ADULT PATIENTS WITH METASTATIC CASTRATION-SENSITIVE PROSTATE CANCER (MCSPC)

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])		Mechanism
action		Bioact sourceMoA source
Androgen receptor Nuclear hormone receptor INHIBITOR IC50 7.19 SCIENTIFIC LITERATURE DRUG LABEL
Progesterone receptor Nuclear hormone receptor ANTAGONIST DRUG LABEL
Androgen receptor Transcription factor ANTAGONIST Ki 7.96 IUPHAR

External reference:

IDSource
X05U0N2RCO UNII
4038612 VANDF
C4547776 UMLSCUI
CHEBI:747353 CHEBI
CHEMBL4297185 ChEMBL_ID
67171867 PUBCHEM_CID
DB12941 DRUGBANK_ID
D11045 KEGG_DRUG
10227 INN_ID
C000607739 MESH_SUPPLEMENTAL_RECORD_UI
10439 IUPHAR_LIGAND_ID
789148001 SNOMEDCT_US
789166006 SNOMEDCT_US
321167 MMSL
37249 MMSL
d09337 MMSL
018070 NDDF
2180325 RXNORM
X05U0N2RCO INXIGHT DRUGS

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
NUBEQA HUMAN PRESCRIPTION DRUG LABEL 1 50419-395 TABLET, FILM COATED 300 mg ORAL NDA 32 sections
NUBEQA HUMAN PRESCRIPTION DRUG LABEL 1 50419-395 TABLET, FILM COATED 300 mg ORAL NDA 32 sections