Darolutamide

Summary

Darolutamide (CHEMBL4297185) is an approved small molecule (ATC L02BB06) targeting AR; indicated across 11 conditions including prostate carcinoma and prostate adenocarcinoma.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: L02BB06
• Targets: 1 (AR)
• Indications: 11 conditions
• Clinical trials: 83
• Chemistry: 398.8 Da · C19H19ClN6O2

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL4297185
Name	Darolutamide
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	67171867
ATC	L02BB06
Molecular formula	C19H19ClN6O2
Molecular weight	398.8
InChIKey	BLIJXOOIHRSQRB-PXYINDEMSA-N

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

IUPAC name: N-[(2S)-1-[3-(3-chloro-4-cyanophenyl)pyrazol-1-yl]propan-2-yl]-5-(1-hydroxyethyl)-1H-pyrazole-3-carboxamide

Also known as: BAY 1841788, BAY-1841788, BAY1841788, Darolutamida, Darolutamide, Nubeqa, Odm-201, ODM-201, DAROLUTAMIDE

Patent coverage: 858 distinct patent families (1,977 SureChEMBL compound mentions), from 3 matched compound structure(s). One matched structure accounts for 1,912 (97%) of the total. Mentions count patents naming the compound (not distinct inventions), so promiscuous / reference molecules inflate the mention figure — families are the dedup metric.

Targets

Targets

Primary targets (GtoPdb curated mechanism): the Cancer dependency column is the DepMap CRISPR fitness signal (% of screened cell lines dependent on the target).

Gene	Target	Action	pAffinity	Cancer dependency	UniProt
AR	Androgen receptor	Antagonist	7.59		P10275

Broader ChEMBL bioactivity targets: 1 (assay-derived). Sample: Androgen receptor.

Bioactivity

ChEMBL activities: 16 potent at pChembl ≥ 5 of 16 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
AR	7.96	Ki	11	nM	CHEMBL_ACT_22795671
AR	7.85	Ki	14	nM	CHEMBL_ACT_27072752
AR	7.58	IC50	26	nM	CHEMBL_ACT_22795672
AR	7.58	IC50	26	nM	CHEMBL_ACT_25828644
AR	7.4	IC50	40	nM	CHEMBL_ACT_29211752
AR	7.32	IC50	48	nM	CHEMBL_ACT_25528489
AR	7.22	IC50	60	nM	CHEMBL_ACT_29241896
AR	7.02	IC50	96	nM	CHEMBL_ACT_27072755
AR	6.72	IC50	190	nM	CHEMBL_ACT_29240876
AR	6.34	IC50	453.7	nM	CHEMBL_ACT_29187128
AR	6.33	IC50	470	nM	CHEMBL_ACT_29280497
AR	6.16	IC50	696	nM	CHEMBL_ACT_29241901
AR	6.07	IC50	850	nM	CHEMBL_ACT_29211756
AR	6.06	IC50	880	nM	CHEMBL_ACT_29280494
AR	5.98	IC50	1050	nM	CHEMBL_ACT_29240873
AR	5.37	Ki	4231	nM	CHEMBL_ACT_25528542

Target pathways

Aggregated over 1 target gene(s): AR.

Top Reactome pathways

23 total, by targets touching each:

Pathway	Targets	Genes
Signal Transduction	1	AR
Signaling by Rho GTPases	1	AR
RHO GTPase Effectors	1	AR
Generic Transcription Pathway	1	AR
Cellular responses to stress	1	AR
SUMOylation	1	AR
SUMO E3 ligases SUMOylate target proteins	1	AR
HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand	1	AR
Nuclear Receptor transcription pathway	1	AR
Metabolism of proteins	1	AR
SUMOylation of intracellular receptors	1	AR
RHO GTPases activate PKNs	1	AR
Activated PKN1 stimulates transcription of AR (androgen receptor) regulated genes KLK2 and KLK3	1	AR
Deubiquitination	1	AR
Ub-specific processing proteases	1	AR
Post-translational protein modification	1	AR
RNA Polymerase II Transcription	1	AR
Gene expression (Transcription)	1	AR
Transcriptional regulation by RUNX2	1	AR
RUNX2 regulates osteoblast differentiation	1	AR
RUNX2 regulates bone development	1	AR
Cellular responses to stimuli	1	AR
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1	AR

Dominant GO biological processes

GO term	Targets
negative regulation of transcription by RNA polymerase II	1
MAPK cascade	1
in utero embryonic development	1
regulation of systemic arterial blood pressure	1
epithelial cell morphogenesis	1
transcription by RNA polymerase II	1
signal transduction	1
cell-cell signaling	1
spermatogenesis	1
single fertilization	1
positive regulation of cell population proliferation	1
negative regulation of cell population proliferation	1
male gonad development	1
positive regulation of gene expression	1
male somatic sex determination	1

Indications & clinical

Indications

11 indications (7 at ChEMBL trial phase 4). Phase below is the highest clinical-trial phase recorded for this drug against each disease — not the molecule’s overall approval status (that is in the Summary).

Indication	Trial phase	MONDO	EFO
prostate carcinoma	4	MONDO:0005159	EFO:0001663
prostate adenocarcinoma	4	MONDO:0005082	EFO:0000673
metastatic prostate carcinoma	4	MONDO:0004956	EFO:0000196
neoplasm	4	MONDO:0005070	EFO:0000616
prostate cancer	4	MONDO:0008315	MONDO:0008315
breast neoplasm	2	MONDO:0021100	MONDO:0007254
salivary gland cancer	2	MONDO:0004669	MONDO:0000521
granulosa cell tumor	2	MONDO:0006036	MONDO:0020541

3 further indication records had no mapped disease name (EFO/MeSH-only) or were duplicates, and are omitted.

Clinical trials

Total trials: 83.

Phase distribution

Phase	Trials
PHASE2	32
PHASE3	16
PHASE1	16
PHASE1/PHASE2	7
Not specified	7
PHASE4	2
EARLY_PHASE1	2
PHASE2/PHASE3	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT06627530	PHASE4	ACTIVE_NOT_RECRUITING	COACTION Trial - COmbination Androgen bloCkade in inTermediate to hIgh-risk prOstate caNcer
NCT06660862	PHASE4	NOT_YET_RECRUITING	Evaluating Treatment Outcomes Using Darolutamide and Androgen Deprivation Therapy in Patients With Metastatic Hormone-Sensitive Prostate Cancer.
NCT03903835	PHASE3	RECRUITING	ProBio: A Biomarker Driven Study in Patients With Metastatic Prostate Cancer
NCT04136353	PHASE3	ACTIVE_NOT_RECRUITING	Darolutamide Augments Standard Therapy for Localised Very High-Risk Cancer of the Prostate
NCT04484818	PHASE3	ACTIVE_NOT_RECRUITING	Testing the Addition of Darolutamide to Hormonal Therapy (Androgen Deprivation Therapy [ADT]) After Surgery for Men With High-Risk Prostate Cancer, The ERADICATE Study
NCT04916613	PHASE3	RECRUITING	ADT +/- Darolutamide in de Novo Metastatic Prostate Cancer Patients With Vulnerable Functional Ability (PEACE6-Vulnerable)
NCT05050084	PHASE3	ACTIVE_NOT_RECRUITING	Two Studies for Patients With Unfavorable Intermediate Risk Prostate Cancer Testing Less Intense Treatment for Patients With a Low Gene Risk Score and Testing a More Intense Treatment for Patients With a Higher Gene Risk Score, The Guidance Trial
NCT05116475	PHASE3	RECRUITING	Evaluation of dAroLutamide Addition to anDrogen Deprivation Therapy and radIatioN Therapy in Newly Diagnosed Prostate Cancer With Pelvic Lymph Nodes Metastases
NCT05676203	PHASE3	ACTIVE_NOT_RECRUITING	A Trial Comparing Docetaxel 75 mg/m2 (3w) Versus Docetaxel 50 mg/m2 (2w) in Combination With Darolutamide + ADT in mHSPC Patients
NCT05794906	PHASE3	ACTIVE_NOT_RECRUITING	A Study to Compare Darolutamide Given With Androgen Deprivation Therapy (ADT) and Placebo Given With ADT in Men With Hormone Sensitive Prostate Cancer and Raise of Prostate Specific Antigen (PSA) Levels After Local Therapies
NCT06120491	PHASE3	ACTIVE_NOT_RECRUITING	Saruparib (AZD5305) vs Placebo in Men With Metastatic Castration-Sensitive Prostate Cancer Receiving Physician’s Choice New Hormonal Agents
NCT06177015	PHASE3	RECRUITING	Intermittent Darolutamide Treatment in the Triple Therapy of mHSPC
NCT06276465	PHASE3	RECRUITING	Treatment With Darolutamide +/- Radiation Therapy for Patients With a Castration Resistant Cancer and Metastases Detected by Functional Imaging
NCT06282588	PHASE2/PHASE3	RECRUITING	Treatment of High-Risk Prostate Cancer Guided by Novel Diagnostic Radio- and Molecular Tracers
NCT06625970	PHASE3	RECRUITING	Study Evaluating the Efficacy and Safety of Darolutamide and Stereotactic Dose Escalated Radiotherapy in Patients With Localized Prostate Cancer and High-risk Features of Relapse
NCT07611110	PHASE3	RECRUITING	AZD2265 Compared With Standard of Care in PSMA-positive Metastatic Castration-resistant Prostate Cancer (VECTRA-01)
NCT02799602	PHASE3	COMPLETED	Darolutamide in Addition to Standard Androgen Deprivation Therapy and Docetaxel in Metastatic Hormone-Sensitive Prostate Cancer
NCT04237584	PHASE3	TERMINATED	A Study Comparing ARB With Radium-223 vs ARB Therapy With Placebo and the Effect Upon Survival for mCRPC Patients
NCT05771896	PHASE3	WITHDRAWN	Darolutamide With Radium-223 or Placebo and the Effect on Radiological Progression-Free Survival for Patients With mCSPC
NCT02972060	PHASE2	ACTIVE_NOT_RECRUITING	ODM-201 vs Androgen Deprivation Therapy in Hormone naïve Prostate Cancer
NCT03385655	PHASE2	ACTIVE_NOT_RECRUITING	Prostate Cancer Biomarker Enrichment and Treatment Selection
NCT04025372	PHASE2	ACTIVE_NOT_RECRUITING	INTREPId (INTermediate Risk Erection PreservatIon Trial)
NCT04070209	PHASE2	ACTIVE_NOT_RECRUITING	Management of Oligoprogressive Castration Resistant Prostate Cancer (PCS X)
NCT04176081	PHASE2	NOT_YET_RECRUITING	Study of Radiation Therapy in Combination With Darolutamide + Degarelix in Intermediate Risk Prostate Cancer
NCT04319783	PHASE2	ACTIVE_NOT_RECRUITING	Darolutamide + Consolidation Radiotherapy in Advanced Prostate Cancer Detected by PSMA
NCT04335682	PHASE2	ACTIVE_NOT_RECRUITING	Androgen Receptor Directed Therapy on Cognitive Function in Patients Treated With Darolutamide or Enzalutamide
NCT04558866	PHASE2	ACTIVE_NOT_RECRUITING	Extreme Bipolar Androgen Therapy With Darolutamide and Testosterone Cypionate in Patients With Metastatic Castration-Resistant Prostate Cancer (ExBAT Trial)
NCT05059236	PHASE2	ACTIVE_NOT_RECRUITING	A Study to Learn How Well Darolutamide Administered Together With Androgen Deprivation Therapy (ADT) Works in Men With Metastatic Hormone-sensitive Prostate Cancer. Results Will be Compared With ADT Alone From a Previously Conducted Study.
NCT05272709	PHASE1/PHASE2	RECRUITING	TT-702 in Patients With Advanced Solid Tumours.
NCT05367440	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Study of AZD5305 When Given in Combination With New Hormonal Agents in Patients With Metastatic Prostate Cancer
NCT05669664	PHASE2	ACTIVE_NOT_RECRUITING	Testing the Anti-cancer Drug Darolutamide in Patients With Testosterone-Driven Salivary Gland Cancers
NCT05762536	PHASE2	RECRUITING	Docetaxel or Cabazitaxel With or Without Darolutamide in mCRPC
NCT06029036	PHASE2	RECRUITING	A Phase II Neoadjuvant Study of Darolutamide Plus ADT in Men With Localized Prostate Cancer
NCT06169124	PHASE2	ACTIVE_NOT_RECRUITING	Study to Test the Drug Darolutamide Along With the Drugs Leuprolide Acetate and Exemestane in Patients With Recurrent Ovarian Granulosa Cell Tumors
NCT06173362	PHASE2	RECRUITING	Abiraterone and Prednisone or Darolutamide for the Treatment of Advanced Prostate Cancer
NCT06190899	PHASE1/PHASE2	RECRUITING	Gedatolisib in Combination With Darolutamide in Metastatic Castration-Resistant Prostate Cancer
NCT06378866	PHASE2	RECRUITING	Stereotactic Body Radiation Therapy Plus Immediate or Delayed Androgen Receptor Pathway Inhibitor and Androgen Deprivation Therapy or Salvage Radiation Therapy for the Treatment of Prostate Cancer, DIVINE Trial
NCT06401980	PHASE2	RECRUITING	Darolutamide in Metastatic Castration-Resistant Prostate Cancer (mCRPC)
NCT06463457	PHASE2	ACTIVE_NOT_RECRUITING	Comeback From Long coursE Androgen Deprivation Therapy (ADT) With RElugolix and Darolutamide (CLEARED)
NCT06575257	PHASE2	RECRUITING	Neoadjuvant Therapy of Darolutamide Plus ADT for High Risk Prostate Cancer

Clinical evidence (CIViC)

No CIViC predictive evidence (expected for non-precision-medicine drugs).

Pharmacology

Pharmacogenomics

No PharmGKB pharmacogenomic data curated for this drug.

Related molecules

Related molecules

Molecules sharing ≥1 of this drug’s curated primary targets, merged from two biobtree sources and ranked by shared-target count, then clinical phase: ChEMBL clinical-stage candidates (development phase ≥2) and PubChem drug-class bioactivity (approved / known drugs acting on the target). Deduplicated by drug name; the drug’s own salt forms are excluded. Note: for a drug with few primary targets a shared-target match can reflect off-target / promiscuous binding rather than the same therapeutic mechanism — the phase ordering surfaces bona-fide therapeutics first.

129 molecules share ≥1 primary target. Top 60 by shared-target count:

Molecule	Source	Status	Shared targets
MEGESTROL	ChEMBL + PubChem	Phase 4 (approved)	AR
ABIRATERONE	ChEMBL	Phase 4 (approved)	AR
APALUTAMIDE	ChEMBL	Phase 4 (approved)	AR
ARIPIPRAZOLE	ChEMBL	Phase 4 (approved)	AR
BECLOMETHASONE DIPROPIONATE	ChEMBL	Phase 4 (approved)	AR
BETAMETHASONE	ChEMBL	Phase 4 (approved)	AR
BICALUTAMIDE	ChEMBL	Phase 4 (approved)	AR
BITHIONOL	ChEMBL	Phase 4 (approved)	AR
BROMHEXINE	ChEMBL	Phase 4 (approved)	AR
BUDESONIDE	ChEMBL	Phase 4 (approved)	AR
CHLORMADINONE	ChEMBL	Phase 4 (approved)	AR
CLARITHROMYCIN	ChEMBL	Phase 4 (approved)	AR
CLASCOTERONE	ChEMBL	Phase 4 (approved)	AR
CLOCORTOLONE PIVALATE	ChEMBL	Phase 4 (approved)	AR
CLOMIPHENE	ChEMBL	Phase 4 (approved)	AR
CORTISONE	ChEMBL	Phase 4 (approved)	AR
CYCLOFENIL	ChEMBL	Phase 4 (approved)	AR
DESOGESTREL	ChEMBL	Phase 4 (approved)	AR
DESOXIMETASONE	ChEMBL	Phase 4 (approved)	AR
DEXAMETHASONE	ChEMBL	Phase 4 (approved)	AR
DIETHYLSTILBESTROL	ChEMBL	Phase 4 (approved)	AR
DIFLORASONE DIACETATE	ChEMBL	Phase 4 (approved)	AR
DORZOLAMIDE	ChEMBL	Phase 4 (approved)	AR
DROSPIRENONE	ChEMBL	Phase 4 (approved)	AR
DYDROGESTERONE	ChEMBL	Phase 4 (approved)	AR
ENZALUTAMIDE	ChEMBL	Phase 4 (approved)	AR
EPLERENONE	ChEMBL	Phase 4 (approved)	AR
ESTRADIOL	ChEMBL	Phase 4 (approved)	AR
ESTRADIOL CYPIONATE	ChEMBL	Phase 4 (approved)	AR
ESTRADIOL VALERATE	ChEMBL	Phase 4 (approved)	AR
ESTRIOL	ChEMBL	Phase 4 (approved)	AR
ESTRONE	ChEMBL	Phase 4 (approved)	AR
ETHINYL ESTRADIOL	ChEMBL	Phase 4 (approved)	AR
ETHYNODIOL DIACETATE	ChEMBL	Phase 4 (approved)	AR
ETONOGESTREL	ChEMBL	Phase 4 (approved)	AR
FLUMETHASONE PIVALATE	ChEMBL	Phase 4 (approved)	AR
FLUOCINOLONE ACETONIDE	ChEMBL	Phase 4 (approved)	AR
FLUOCINONIDE	ChEMBL	Phase 4 (approved)	AR
FLUOXYMESTERONE	ChEMBL	Phase 4 (approved)	AR
FLURANDRENOLIDE	ChEMBL	Phase 4 (approved)	AR
FLUTAMIDE	ChEMBL	Phase 4 (approved)	AR
FLUTICASONE FUROATE	ChEMBL	Phase 4 (approved)	AR
FLUTICASONE PROPIONATE	ChEMBL	Phase 4 (approved)	AR
HALCINONIDE	ChEMBL	Phase 4 (approved)	AR
HALOBETASOL PROPIONATE	ChEMBL	Phase 4 (approved)	AR
HEXACHLOROPHENE	ChEMBL	Phase 4 (approved)	AR
HEXESTROL	ChEMBL	Phase 4 (approved)	AR
HYDROCORTISONE	ChEMBL	Phase 4 (approved)	AR
INDOMETHACIN	ChEMBL	Phase 4 (approved)	AR
LEVONORGESTREL	ChEMBL	Phase 4 (approved)	AR
MEDROXYPROGESTERONE	ChEMBL	Phase 4 (approved)	AR
METHYLPREDNISOLONE	ChEMBL	Phase 4 (approved)	AR
MIFEPRISTONE	ChEMBL	Phase 4 (approved)	AR
MOMETASONE FUROATE	ChEMBL	Phase 4 (approved)	AR
NILUTAMIDE	ChEMBL	Phase 4 (approved)	AR
NOMEGESTROL	ChEMBL	Phase 4 (approved)	AR
NORETHINDRONE	ChEMBL	Phase 4 (approved)	AR
NORETHYNODREL	ChEMBL	Phase 4 (approved)	AR
OXANDROLONE	ChEMBL	Phase 4 (approved)	AR
OXICONAZOLE	ChEMBL	Phase 4 (approved)	AR