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Details

Stereochemistry EPIMERIC
Molecular Formula C19H19ClN6O2
Molecular Weight 398.8468
Optical Activity UNSPECIFIED
Defined Stereocenters 1 / 2
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of DAROLUTAMIDE

SMILES

C[C@@]([H])(Cn1ccc(-c2ccc(C#N)c(c2)Cl)n1)NC(=O)c3cc(C([H])(C)O)[nH]n3

InChI

InChIKey=BLIJXOOIHRSQRB-PXYINDEMSA-N
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

HIDE SMILES / InChI

Description
Curator's Comment:: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/26137992 | https://www.ncbi.nlm.nih.gov/pubmed/26313416

ODM-201 (also known as BAY-1841788) is a non-steroidal antiandrogen, specifically, a full and high-affinity antagonist of the androgen receptor (AR), that is under development by Orion and Bayer HealthCare for the treatment of advanced, castration-resistant prostate cancer (CRPC). ODM-201 appears to negligibly cross the blood-brain-barrier. This is beneficial due to the reduced risk of seizures and other central side effects from off-target GABAA receptor inhibition that tends to occur in non-steroidal antiandrogens that are structurally similar to enzalutamide. Moreover, in accordance with its lack of central penetration, ODM-201 does not seem to increase testosterone levels in mice or humans, unlike other non-steroidal antiandrogens. Another advantage is that ODM-201 has been found to block the activity of all tested/well-known mutant ARs in prostate cancer, including the recently-identified clinically-relevant F876L mutation. ODM-201 has been studied in phase I and phase II clinical trials and has thus far been found to be effective and well-tolerated, with the most commonly reported side effects including fatigue, nausea, and diarrhea. No seizures have been observed.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
65.0 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
4.79 mg/L
600 mg 2 times / day steady-state, oral
dose: 600 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
ODM-201 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
52.82 μg × h/mL
600 mg 2 times / day steady-state, oral
dose: 600 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
ODM-201 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
20 h
600 mg 2 times / day steady-state, oral
dose: 600 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
ODM-201 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
600 mg 2 times / day steady, oral
Recommended
Dose: 600 mg, 2 times / day
Route: oral
Route: steady
Dose: 600 mg, 2 times / day
Sources:
unhealthy, 74 years (range: 48–95 years)
n = 954
Health Status: unhealthy
Condition: non-metastatic castration-resistant prostate cancer
Age Group: 74 years (range: 48–95 years)
Sex: M
Population Size: 954
Sources:
Disc. AE: Cardiac failure, Hypertension...
AEs leading to
discontinuation/dose reduction:
Cardiac failure (0.4%)
Hypertension (0.6%)
Diarrhea (0.5%)
Pneumonia (0.5%)
Fatigue (0.7%)
Hypertension (0.3%)
Nausea (0.3%)
Sources:
900 mg 2 times / day steady, oral
Highest studied dose
Dose: 900 mg, 2 times / day
Route: oral
Route: steady
Dose: 900 mg, 2 times / day
Sources:
unhealthy
n = 3
Health Status: unhealthy
Condition: non-metastatic castration-resistant prostate cancer
Population Size: 3
Sources:
AEs

AEs

AESignificanceDosePopulation
Hypertension 0.3%
Disc. AE
600 mg 2 times / day steady, oral
Recommended
Dose: 600 mg, 2 times / day
Route: oral
Route: steady
Dose: 600 mg, 2 times / day
Sources:
unhealthy, 74 years (range: 48–95 years)
n = 954
Health Status: unhealthy
Condition: non-metastatic castration-resistant prostate cancer
Age Group: 74 years (range: 48–95 years)
Sex: M
Population Size: 954
Sources:
Nausea 0.3%
Disc. AE
600 mg 2 times / day steady, oral
Recommended
Dose: 600 mg, 2 times / day
Route: oral
Route: steady
Dose: 600 mg, 2 times / day
Sources:
unhealthy, 74 years (range: 48–95 years)
n = 954
Health Status: unhealthy
Condition: non-metastatic castration-resistant prostate cancer
Age Group: 74 years (range: 48–95 years)
Sex: M
Population Size: 954
Sources:
Cardiac failure 0.4%
Disc. AE
600 mg 2 times / day steady, oral
Recommended
Dose: 600 mg, 2 times / day
Route: oral
Route: steady
Dose: 600 mg, 2 times / day
Sources:
unhealthy, 74 years (range: 48–95 years)
n = 954
Health Status: unhealthy
Condition: non-metastatic castration-resistant prostate cancer
Age Group: 74 years (range: 48–95 years)
Sex: M
Population Size: 954
Sources:
Diarrhea 0.5%
Disc. AE
600 mg 2 times / day steady, oral
Recommended
Dose: 600 mg, 2 times / day
Route: oral
Route: steady
Dose: 600 mg, 2 times / day
Sources:
unhealthy, 74 years (range: 48–95 years)
n = 954
Health Status: unhealthy
Condition: non-metastatic castration-resistant prostate cancer
Age Group: 74 years (range: 48–95 years)
Sex: M
Population Size: 954
Sources:
Pneumonia 0.5%
Disc. AE
600 mg 2 times / day steady, oral
Recommended
Dose: 600 mg, 2 times / day
Route: oral
Route: steady
Dose: 600 mg, 2 times / day
Sources:
unhealthy, 74 years (range: 48–95 years)
n = 954
Health Status: unhealthy
Condition: non-metastatic castration-resistant prostate cancer
Age Group: 74 years (range: 48–95 years)
Sex: M
Population Size: 954
Sources:
Hypertension 0.6%
Disc. AE
600 mg 2 times / day steady, oral
Recommended
Dose: 600 mg, 2 times / day
Route: oral
Route: steady
Dose: 600 mg, 2 times / day
Sources:
unhealthy, 74 years (range: 48–95 years)
n = 954
Health Status: unhealthy
Condition: non-metastatic castration-resistant prostate cancer
Age Group: 74 years (range: 48–95 years)
Sex: M
Population Size: 954
Sources:
Fatigue 0.7%
Disc. AE
600 mg 2 times / day steady, oral
Recommended
Dose: 600 mg, 2 times / day
Route: oral
Route: steady
Dose: 600 mg, 2 times / day
Sources:
unhealthy, 74 years (range: 48–95 years)
n = 954
Health Status: unhealthy
Condition: non-metastatic castration-resistant prostate cancer
Age Group: 74 years (range: 48–95 years)
Sex: M
Population Size: 954
Sources:
OverviewDrug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
no [IC50 4.46 uM]
unlikely (co-administration study)
Comment: no change in the total and renal clearance of rosuvastatin by darolutamide
Page: 72.0
no [IC50 >10 uM]
no [IC50 >10 uM]
no [IC50 >10 uM]
no [IC50 >2 uM]
no [IC50 >2 uM]
no [IC50 >2 uM]
no [IC50 >300 uM]
no [IC50 >50 uM]
no [IC50 >50 uM]
no [IC50 >50 uM]
no [IC50 >50 uM]
no [IC50 >50 uM]
no [IC50 >60 uM]
no
no
no
no
no
no
no
no
no
weak
weak (co-administration study)
Comment: decreased the mean exposure (AUC) and Cmax of midazolam by 29% and 32%, respectively; did not show any increase but a mean decrease of less than 20% in the mean exposure (AUC) and Cmax of non-conjugated or total dabigatran
Page: 71.0
yes [IC50 0.567 uM]
yes [IC50 1.33 uM]
yes (co-administration study)
Comment: showed a 5.2-fold increase in AUC and a 4.9-fold increase in Cmax of rosuvastatin
Page: 72.0
yes [IC50 16.4 uM]
yes [IC50 16.8 uM]
unlikely (co-administration study)
Comment: no change in the total and renal clearance of rosuvastatin by darolutamide
Page: 72.0
yes [IC50 2.57 uM]
yes [IC50 2.96 uM]
yes [IC50 32.3 uM]
yes [IC50 39.3 uM]
unlikely (co-administration study)
Comment: no change in the total and renal clearance of rosuvastatin by darolutamide
Page: 72.0
yes [IC50 9.5 uM]
yes [IC50 >10 uM]
yes [IC50 >10 uM]
yes [IC50 >10 uM]
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
yes
yes
yes
yes
yes
yes
yes
yes (co-administration study)
Comment: significant reduction in darolutamide exposure (72% reduction in darolutamide AUC72) when it is concomitantly used with rifampin; Inhibition of CYP3A4 and P-gp by itraconazole increased darolutamide exposure (AUC72) by 1.7­ fold
Page: 72.0
yes
yes (co-administration study)
Comment: significant reduction in darolutamide exposure (72% reduction in darolutamide AUC72) when it is concomitantly used with rifampin; Inhibition of CYP3A4 and P-gp by itraconazole increased darolutamide exposure (AUC72) by 1.7­ fold
Page: 72.0
Tox targets
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
ODM-201: a new-generation androgen receptor inhibitor in castration-resistant prostate cancer.
2015
ODM-201 tablets complete phase I.
2015 Dec
Patents

Sample Use Guides

In the Phase II patients were treated orally with 200 mg/day, 400 mg/day or 1400 mg/day of ODM-201.
Route of Administration: Oral
Antagonism to wtAR was determined using AR-HEK293 cells treated with ODM-201 up to 1 uM. The cells were treated with test compounds and 0.45 nM testosterone in steroid-free assay medium. After 24 hours cells were lysed and luciferase activity was measured.
Name Type Language
DAROLUTAMIDE
INN   WHO-DD  
INN  
Official Name English
NUBEQA
Brand Name English
1H-PYRAZOLE-3-CARBOXAMIDE, N-((1S)-2-(3-(3-CHLORO-4-CYANOPHENYL)-1H-PYRAZOL-1-YL)-1-METHYLETHYL)-5-(1-HYDROXYETHYL)-
Systematic Name English
N-((2S)-1-(3-(3-CHLORO-4-CYANOPHENYL)-1H-PYRAZOL- 1-YL)PROPAN-2-YL)-5-((1RS)-1-HYDROXYETHYL)-1H-PYRAZOLE- 3-CARBOXAMIDE
Systematic Name English
ODM-201
Code English
DAROLUTAMIDE [WHO-DD]
Common Name English
DAROLUTAMIDE [MI]
Common Name English
DAROLUTAMIDE [ORANGE BOOK]
Common Name English
DAROLUTAMIDE [INN]
Common Name English
BAY1841788
Code English
DAROLUTAMIDE [USAN]
Common Name English
BAY-1841788
Code English
Classification Tree Code System Code
NCI_THESAURUS C146993
Created by admin on Sat Jun 26 15:37:26 UTC 2021 , Edited by admin on Sat Jun 26 15:37:26 UTC 2021
Code System Code Type Description
MERCK INDEX
M12159
Created by admin on Sat Jun 26 15:37:26 UTC 2021 , Edited by admin on Sat Jun 26 15:37:26 UTC 2021
PRIMARY
DRUG BANK
DB12941
Created by admin on Sat Jun 26 15:37:26 UTC 2021 , Edited by admin on Sat Jun 26 15:37:26 UTC 2021
PRIMARY
INN
10227
Created by admin on Sat Jun 26 15:37:26 UTC 2021 , Edited by admin on Sat Jun 26 15:37:26 UTC 2021
PRIMARY
EVMPD
SUB185326
Created by admin on Sat Jun 26 15:37:26 UTC 2021 , Edited by admin on Sat Jun 26 15:37:26 UTC 2021
PRIMARY
DRUG CENTRAL
5334
Created by admin on Sat Jun 26 15:37:26 UTC 2021 , Edited by admin on Sat Jun 26 15:37:26 UTC 2021
PRIMARY
CAS
1598419-57-8
Created by admin on Sat Jun 26 15:37:26 UTC 2021 , Edited by admin on Sat Jun 26 15:37:26 UTC 2021
NO STRUCTURE GIVEN
ChEMBL
CHEMBL3545294
Created by admin on Sat Jun 26 15:37:26 UTC 2021 , Edited by admin on Sat Jun 26 15:37:26 UTC 2021
PRIMARY
FDA UNII
X05U0N2RCO
Created by admin on Sat Jun 26 15:37:26 UTC 2021 , Edited by admin on Sat Jun 26 15:37:26 UTC 2021
PRIMARY
RXCUI
2180325
Created by admin on Sat Jun 26 15:37:26 UTC 2021 , Edited by admin on Sat Jun 26 15:37:26 UTC 2021
PRIMARY
NCI_THESAURUS
C104748
Created by admin on Sat Jun 26 15:37:26 UTC 2021 , Edited by admin on Sat Jun 26 15:37:26 UTC 2021
PRIMARY
CAS
1297538-32-9
Created by admin on Sat Jun 26 15:37:26 UTC 2021 , Edited by admin on Sat Jun 26 15:37:26 UTC 2021
PRIMARY
WIKIPEDIA
ODM-201
Created by admin on Sat Jun 26 15:37:26 UTC 2021 , Edited by admin on Sat Jun 26 15:37:26 UTC 2021
PRIMARY
PUBCHEM
67171867
Created by admin on Sat Jun 26 15:37:26 UTC 2021 , Edited by admin on Sat Jun 26 15:37:26 UTC 2021
PRIMARY