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Details

Stereochemistry EPIMERIC
Molecular Formula C19H19ClN6O2
Molecular Weight 398.846
Optical Activity UNSPECIFIED
Defined Stereocenters 1 / 2
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of DAROLUTAMIDE

SMILES

C[C@@H](CN1C=CC(=N1)C2=CC(Cl)=C(C=C2)C#N)NC(=O)C3=NNC(=C3)C(C)O

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

Molecular Formula C19H19ClN6O2
Molecular Weight 398.846
Charge 0
Count
Stereochemistry EPIMERIC
Additional Stereochemistry
Defined Stereocenters 1 / 2
E/Z Centers 0
Optical Activity UNSPECIFIED

Description

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.

CNS Activity

Originator

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
65.0 nM [IC50]
Conditions
PubMed

PubMed

TitleDatePubMed
Patents

Sample Use Guides

In Vivo Use Guide
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
In Vitro Use Guide
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.
Substance Class Chemical
Created
by admin
on Mon Oct 21 20:18:36 UTC 2019
Edited
by admin
on Mon Oct 21 20:18:36 UTC 2019
Record UNII
X05U0N2RCO
Record Status Validated (UNII)
Record Version
  • Download
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 [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 Mon Oct 21 20:18:36 UTC 2019 , Edited by admin on Mon Oct 21 20:18:36 UTC 2019
Code System Code Type Description
INN
10227
Created by admin on Mon Oct 21 20:18:36 UTC 2019 , Edited by admin on Mon Oct 21 20:18:36 UTC 2019
PRIMARY
EVMPD
SUB185326
Created by admin on Mon Oct 21 20:18:36 UTC 2019 , Edited by admin on Mon Oct 21 20:18:36 UTC 2019
PRIMARY
CAS
1598419-57-8
Created by admin on Mon Oct 21 20:18:36 UTC 2019 , Edited by admin on Mon Oct 21 20:18:36 UTC 2019
NO STRUCTURE GIVEN
ChEMBL
CHEMBL3545294
Created by admin on Mon Oct 21 20:18:36 UTC 2019 , Edited by admin on Mon Oct 21 20:18:36 UTC 2019
PRIMARY
CAS
1297538-32-9
Created by admin on Mon Oct 21 20:18:36 UTC 2019 , Edited by admin on Mon Oct 21 20:18:36 UTC 2019
PRIMARY
WIKIPEDIA
ODM-201
Created by admin on Mon Oct 21 20:18:36 UTC 2019 , Edited by admin on Mon Oct 21 20:18:36 UTC 2019
PRIMARY
PUBCHEM
67171867
Created by admin on Mon Oct 21 20:18:36 UTC 2019 , Edited by admin on Mon Oct 21 20:18:36 UTC 2019
PRIMARY
Related Record Type Details
TRANSPORTER -> SUBSTRATE
MAJOR
METABOLIC ENZYME -> SUBSTRATE
EXCRETED UNCHANGED
AMOUNT EXCRETED
URINE
METABOLIC ENZYME -> SUBSTRATE
METABOLIC ENZYME -> SUBSTRATE
BINDER->LIGAND
BINDING
TRANSPORTER -> SUBSTRATE
MINOR
METABOLIC ENZYME -> SUBSTRATE
TARGET -> AGONIST
BINDING
METABOLIC ENZYME -> SUBSTRATE
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Tmax PHARMACOKINETIC MULTIPLE ORAL ADMINISTRATION

blood-to-plasma ratio PHARMACOKINETIC
Biological Half-life PHARMACOKINETIC
Volume of Distribution PHARMACOKINETIC