Enzalutamide

Summary

Enzalutamide (CHEMBL1082407) is an approved small-molecule antineoplastic agent (ATC L02BB04) targeting AR; indicated across 23 conditions including prostate adenocarcinoma and prostate carcinoma; with CIViC clinical evidence for 13 variant-indication associations (e.g. ATR Loss-of-function in castration-resistant prostate carcinoma).

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: L02BB04
• Targets: 1 (AR)
• Indications: 23 conditions
• Clinical trials: 314
• Precision-oncology evidence (CIViC): 13 variant–indication associations
• Chemistry: 464.4 Da · C21H16F4N4O2S

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL1082407
Name	Enzalutamide
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	15951529
ChEBI	CHEBI:68534
ATC	L02BB04
Molecular formula	C21H16F4N4O2S
Molecular weight	464.4
InChIKey	WXCXUHSOUPDCQV-UHFFFAOYSA-N

SMILES: CC1(C(=O)N(C(=S)N1C2=CC(=C(C=C2)C(=O)NC)F)C3=CC(=C(C=C3)C#N)C(F)(F)F)C

IUPAC name: 4-[3-[4-cyano-3-(trifluoromethyl)phenyl]-5,5-dimethyl-4-oxo-2-sulfanylideneimidazolidin-1-yl]-2-fluoro-N-methylbenzamide

ChEBI definition: A benzamide obtained by formal condensation of the carboxy group of 4-{3-[4-cyano-3-(trifluoromethyl)phenyl]-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl}-2-fluorobenzoic acid with methylamine. Used for the treatment of of metastatic castration-resistant prostate cancer.

Pharmacological roles (ChEBI): antineoplastic agent, androgen antagonist.

Also known as: Enzalutamida, Enzalutamide, Mdv 3100, MDV-3100, MDV3100, Xtandi, ENZALUTAMIDE, SID137275964, enzalutamide, EnzalutamideÊ, EnzalutamideÂ, Enzalatamide

Parent form; salt/anhydrous children: CHEMBL4594421

Patent coverage: 4,044 distinct patent families (9,652 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 8,935 (93%) 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	6.66		P10275

Broader ChEMBL bioactivity targets: 9 (assay-derived). Sample: Androgen receptor, Glucocorticoid receptor, Thromboxane A2 receptor, Progesterone receptor, GABA-A receptor; anion channel, Prostate-specific antigen, Cannabinoid receptor 1, Androgen receptor, Nuclear receptor subfamily 1 group I member 2.

Bioactivity

ChEMBL activities: 87 potent at pChembl ≥ 5 of 96 total. Top 100 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
AR	7.85	IC50	14	nM	CHEMBL_ACT_24518023
AR	7.77	Ki	17	nM	CHEMBL_ACT_23199597
AR	7.68	IC50	21	nM	CHEMBL_ACT_16768432
AR	7.6	IC50	25	nM	CHEMBL_ACT_24697096
AR	7.55	Ki	28.2	nM	CHEMBL_ACT_15634041
AR	7.44	IC50	36	nM	CHEMBL_ACT_22473288
AR	7.44	IC50	36	nM	CHEMBL_ACT_25828642
AR	7.42	IC50	38	nM	CHEMBL_ACT_23199593
AR	7.31	EC50	49	nM	CHEMBL_ACT_13344972
AR	7.3	IC50	50	nM	CHEMBL_ACT_18809240
AR	7.22	AC50	60	nM	CHEMBL_ACT_25203728
AR	7.22	IC50	60	nM	CHEMBL_ACT_29240760
AR	7.21	EC50	61.8	nM	CHEMBL_ACT_23199621
AR	7.16	IC50	70	nM	CHEMBL_ACT_24406846
AR	7.12	IC50	75	nM	CHEMBL_ACT_23238341
AR	7.1	IC50	80	nM	CHEMBL_ACT_24517993
AR	7.07	Ki	86	nM	CHEMBL_ACT_22795673
AR	7.05	IC50	90	nM	CHEMBL_ACT_18809254
AR	7	IC50	99	nM	CHEMBL_ACT_25932433
AR	6.96	IC50	110	nM	CHEMBL_ACT_29211655
AR	6.95	IC50	112.3	nM	CHEMBL_ACT_24747463
AR	6.95	IC50	112.3	nM	CHEMBL_ACT_25514439
AR	6.93	IC50	117	nM	CHEMBL_ACT_23199665
AR	6.93	IC50	117	nM	CHEMBL_ACT_23280986
KLK3	6.89	IC50	130	nM	CHEMBL_ACT_22473293
AR	6.85	IC50	140	nM	CHEMBL_ACT_29241871
AR	6.85	IC50	140	nM	CHEMBL_ACT_29280401
AR	6.75	EC50	180	nM	CHEMBL_ACT_19474719
AR	6.74	IC50	183.4	nM	CHEMBL_ACT_29191560
AR	6.73	IC50	186.4	nM	CHEMBL_ACT_25941858
AR	6.73	IC50	186.4	nM	CHEMBL_ACT_29187013
AR	6.67	IC50	216	nM	CHEMBL_ACT_19293361
AR	6.67	IC50	216	nM	CHEMBL_ACT_22432230
AR	6.67	IC50	216	nM	CHEMBL_ACT_23150027
AR	6.67	IC50	216	nM	CHEMBL_ACT_25528488
AR	6.67	IC50	216	nM	CHEMBL_ACT_28149140
AR	6.67	IC50	216	nM	CHEMBL_ACT_28995983
AR	6.66	IC50	219	nM	CHEMBL_ACT_22795675
AR	6.58	IC50	260	nM	CHEMBL_ACT_29240874
P15207	6.53	IC50	294	nM	CHEMBL_ACT_16772170
AR	6.5	IC50	320	nM	CHEMBL_ACT_29280452
AR	6.47	IC50	340	nM	CHEMBL_ACT_25669121
AR	6.44	IC50	361	nM	CHEMBL_ACT_16653866
P15207	6.44	IC50	361	nM	CHEMBL_ACT_19467348
AR	6.44	IC50	360	nM	CHEMBL_ACT_29280450
AR	6.42	IC50	383.6	nM	CHEMBL_ACT_29191564
AR	6.4	IC50	401	nM	CHEMBL_ACT_29241906
AR	6.38	EC50	420	nM	CHEMBL_ACT_18082132
AR	6.35	IC50	450	nM	CHEMBL_ACT_24836549
AR	6.32	IC50	480	nM	CHEMBL_ACT_24518048
AR	6.31	IC50	492	nM	CHEMBL_ACT_24747428
AR	6.28	IC50	522	nM	CHEMBL_ACT_25514417
AR	6.19	IC50	646.9	nM	CHEMBL_ACT_22487557
AR	6.1	IC50	800	nM	CHEMBL_ACT_25511437
AR	6.1	IC50	800	nM	CHEMBL_ACT_25639172
AR	6.04	EC50	915	nM	CHEMBL_ACT_13344974
AR	5.99	IC50	1031	nM	CHEMBL_ACT_25514431
AR	5.97	EC50	1070	nM	CHEMBL_ACT_24697181
AR	5.96	EC50	1100	nM	CHEMBL_ACT_19447574
AR	5.96	EC50	1100	nM	CHEMBL_ACT_24824291
AR	5.9	IC50	1260	nM	CHEMBL_ACT_18360121
P15207	5.88	IC50	1320	nM	CHEMBL_ACT_18877948
P15207	5.88	IC50	1320	nM	CHEMBL_ACT_19244530
AR	5.71	IC50	1940	nM	CHEMBL_ACT_26775428
AR	5.71	IC50	1970	nM	CHEMBL_ACT_29280496
AR	5.69	IC50	2045	nM	CHEMBL_ACT_29191570
AR	5.68	IC50	2100	nM	CHEMBL_ACT_29241838
AR	5.62	Ki	2370	nM	CHEMBL_ACT_25941971
AR	5.52	IC50	3030	nM	CHEMBL_ACT_22474999
GABRP	5.52	IC50	3000	nM	CHEMBL_ACT_24824307
PGR	5.49	AC50	3210	nM	CHEMBL_ACT_25204661
AR	5.44	Ki	3641	nM	CHEMBL_ACT_19293402
P15207	5.44	Ki	3641	nM	CHEMBL_ACT_22432275
AR	5.44	Ki	3641	nM	CHEMBL_ACT_22877509
P15207	5.44	Ki	3641	nM	CHEMBL_ACT_23150025
AR	5.44	Ki	3641	nM	CHEMBL_ACT_25528541
AR	5.44	Ki	3641	nM	CHEMBL_ACT_28149137
AR	5.44	Ki	3641	nM	CHEMBL_ACT_28598792
AR	5.44	Ki	3641	nM	CHEMBL_ACT_28995980
NR1I2	5.43	AC50	3700	nM	CHEMBL_ACT_25188422
AR	5.4	IC50	3970	nM	CHEMBL_ACT_22473279
AR	5.35	IC50	4460	nM	CHEMBL_ACT_29280461
GABRP	5.32	IC50	4800	nM	CHEMBL_ACT_25514507
AR	5.27	IC50	5336	nM	CHEMBL_ACT_19025714
AR	5.25	IC50	5600	nM	CHEMBL_ACT_13494241
AR	5.19	Kd	6520	nM	CHEMBL_ACT_24697160
AR	5.07	IC50	8610	nM	CHEMBL_ACT_26775431

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

7 approved indications. FDA phase 4, plus an anticancer drug’s labelled cancer uses (which ChEMBL often logs at phase 3).

Indication	Phase	MONDO	EFO
prostate adenocarcinoma	4	MONDO:0005082	EFO:0000673
prostate carcinoma	4	MONDO:0005159	EFO:0001663
metastatic prostate carcinoma	4	MONDO:0004956	EFO:0000196
neoplasm	4	MONDO:0005070	EFO:0000616
prostate cancer	4	MONDO:0008315	MONDO:0008315
breast neoplasm	3	MONDO:0021100	MONDO:0007254
breast carcinoma	3	MONDO:0004989	EFO:0000305

12 diseases in clinical trials (phase 1–3, investigational — not approved indications). Highest ChEMBL trial phase per disease; a non-cancer approved use is occasionally logged at phase 3 here.

Disease (in trials)	Phase	MONDO	EFO
hepatocellular carcinoma	2	MONDO:0007256	EFO:0000182
carcinoma	2	MONDO:0004993	EFO:0000313
mantle cell lymphoma	2	MONDO:0018876	EFO:1001469
ovarian cancer	2	MONDO:0008170	MONDO:0008170
severe acute respiratory syndrome	2	MONDO:0005091	MONDO:0100096
triple-negative breast carcinoma	2	MONDO:0005494	EFO:0005537
uterine corpus cancer	2	MONDO:0006003	EFO:0007532
adenocarcinoma	2	MONDO:0004970	EFO:0000228
tumor of uterus	2	MONDO:0021353	EFO:0003859
kidney disorder	1	MONDO:0005240	EFO:0003086
liver disorder	1	MONDO:0005154	EFO:0001421
exocrine pancreatic carcinoma	1	MONDO:0005192	EFO:0002618

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

Clinical trials

Total trials: 314.

Phase distribution

Phase	Trials
PHASE2	134
PHASE1	58
PHASE3	42
PHASE1/PHASE2	36
Not specified	27
PHASE4	10
PHASE2/PHASE3	5
EARLY_PHASE1	2

Top trials by phase / activity

NCT	Phase	Status	Title
NCT03016741	PHASE4	ACTIVE_NOT_RECRUITING	Cognitive Effects of Androgen Receptor Directed Therapies for Advanced Prostate Cancer
NCT05457257	PHASE4	ACTIVE_NOT_RECRUITING	Clinical Study to Assess the Efficacy and Safety of Olaparib in Chinese Patients With Metastatic Castration-Resistant Prostate Cancer Who Have Failed Prior Treatment With a New Hormonal Agent and Have BRCA1/2 Mutations
NCT01977651	PHASE4	COMPLETED	A Study to Evaluate the Potential Increased Risk of Seizures Among Metastatic Castration-Resistant Prostate Cancer (mCRPC) Patients Treated With Enzalutamide
NCT01995513	PHASE4	COMPLETED	Safety Study of Continued Enzalutamide Treatment In Prostate Cancer Patients
NCT02116582	PHASE4	COMPLETED	A Study to Evaluate Enzalutamide After Abiraterone in Metastatic Castration-Resistant Prostate Cancer
NCT02441517	PHASE4	TERMINATED	A Study of Enzalutamide Re-treatment in Metastatic Castration-resistant Prostate Cancer After Docetaxel and/or Cabazitaxel Treatment
NCT02485691	PHASE4	COMPLETED	Cabazitaxel Versus the Switch to Alternative AR-targeted Agent (Enzalutamide or Abiraterone) in Metastatic Castration-resistant Prostate Cancer (mCRPC) Patients Previously Treated With Docetaxel and Who Rapidly Failed a Prior AR-targeted Agent
NCT02918968	PHASE4	COMPLETED	Study on Enzalutamide and Flutamide in Patients With Castration Resistant Prostate Cancer
NCT03641560	PHASE4	COMPLETED	A Safety and Efficacy Study of Enzalutamide in Indian Patients With Progressive Metastatic Castration-Resistant Prostate Cancer (mCRPC) Previously Treated With Docetaxel-Based Chemotherapy
NCT03927391	PHASE4	COMPLETED	Effect of a Reduced Dose Enzalutamide in Frail (m)CRPC Patients on Cognitive Side Effects
NCT00268476	PHASE2/PHASE3	ACTIVE_NOT_RECRUITING	Systemic Therapy in Advancing or Metastatic Prostate Cancer: Evaluation of Drug Efficacy
NCT02194842	PHASE3	ACTIVE_NOT_RECRUITING	Phase III Radium 223 mCRPC-PEACE III
NCT02319837	PHASE3	ACTIVE_NOT_RECRUITING	Safety and Efficacy Study of Enzalutamide Plus Leuprolide in Patients With Nonmetastatic Prostate Cancer (EMBARK)
NCT02446405	PHASE3	ACTIVE_NOT_RECRUITING	Enzalutamide in First Line Androgen Deprivation Therapy for Metastatic Prostate Cancer
NCT02446444	PHASE3	ACTIVE_NOT_RECRUITING	Enzalutamide in Androgen Deprivation Therapy With Radiation Therapy for High Risk, Clinically Localised, Prostate Cancer
NCT02685397	PHASE2/PHASE3	ACTIVE_NOT_RECRUITING	Management of Castration-Resistant Prostate Cancer with Oligometastases
NCT03768063	PHASE3	ACTIVE_NOT_RECRUITING	A Study in Patients Previously Enrolled in a Genentech and/or F. Hoffmann-La Roche Ltd Sponsored Atezolizumab Study
NCT03834493	PHASE3	ACTIVE_NOT_RECRUITING	Study of Pembrolizumab (MK-3475) Plus Enzalutamide Versus Placebo Plus Enzalutamide in Participants With Metastatic Castration-resistant Prostate Cancer (mCRPC) (MK-3475-641/KEYNOTE-641)
NCT03903835	PHASE3	RECRUITING	ProBio: A Biomarker Driven Study in Patients With Metastatic Prostate Cancer
NCT04076059	PHASE3	ACTIVE_NOT_RECRUITING	An Efficacy and Safety Study of Enzalutamide Plus Androgen Deprivation Therapy (ADT) Versus Placebo Plus ADT in Chinese Patients With Metastatic Hormone Sensitive Prostate Cancer (mHSPC)
NCT04446117	PHASE3	ACTIVE_NOT_RECRUITING	Study of Cabozantinib in Combination With Atezolizumab Versus Second NHT in Subjects With mCRPC
NCT04455750	PHASE3	ACTIVE_NOT_RECRUITING	A Clinical Study Evaluating The Benefit of Adding Rucaparib to Enzalutamide for Men With Metastatic Prostate Cancer That Has Become Resistant To Testosterone-Deprivation Therapy
NCT04647526	PHASE3	ACTIVE_NOT_RECRUITING	Study Evaluating mCRPC Treatment Using PSMA [Lu-177]-PNT2002 Therapy After Second-line Hormonal Treatment
NCT04787744	PHASE2/PHASE3	RECRUITING	Veterans Affairs Seamless Phase II/III Randomized Trial of STAndard Systemic theRapy With or Without PET-directed Local Therapy for Oligometastatic pRosTate Cancer
NCT05112965	PHASE3	ACTIVE_NOT_RECRUITING	An Extension Study in Participants Previously Enrolled in a Genentech and/or F. Hoffmann-La Roche Ltd Sponsored Atezolizumab Study (IMbrella C)
NCT06120491	PHASE3	ACTIVE_NOT_RECRUITING	Saruparib (AZD5305) vs Placebo in Men With Metastatic Castration-Sensitive Prostate Cancer Receiving Physician’s Choice New Hormonal Agents
NCT06136624	PHASE3	RECRUITING	Study of Opevesostat (MK-5684) Versus Alternative NHA in mCRPC (MK-5684-003)
NCT06136650	PHASE3	RECRUITING	A Study of Opevesostat (MK-5684) Versus Alternative Next-generation Hormonal Agent (NHA) in Metastatic Castration-resistant Prostate Cancer (mCRPC) Post One NHA (MK-5684-004)
NCT06520345	PHASE3	RECRUITING	The Study of 177Lu-TLX591 Plus SOC Versus SOC Alone in Patients With mCRPC (ProstACT Global)
NCT06551324	PHASE3	ACTIVE_NOT_RECRUITING	A Study to Learn About the Investigational Medicine Called PF-06821497 (Mevrometostat) in Men With mCRPC Who Were Previously Treated With Abiraterone Acetate for Prostate Cancer (MEVPRO-1).
NCT06592924	PHASE3	RECRUITING	Docetaxel to Androgen Receptor Pathway Inhibitors in Patients With Metastatic Castration Sensitive Prostate Cancer and Suboptimal PSA Response
NCT06629779	PHASE3	RECRUITING	A Study to Learn How PF-06821497 (Mevrometostat) Works in Men With Metastatic Castration-resistant Prostate Cancer.
NCT06691984	PHASE3	ACTIVE_NOT_RECRUITING	Phase 3 Study of Xaluritamig vs Cabazitaxel or Second Androgen Receptor-Directed Therapy in Participants With Progressive Metastatic Castration-Resistant Prostate Cancer (XALute)
NCT06764485	PHASE3	RECRUITING	A Study to Compare the Efficacy and Safety of BMS-986365 Versus the Investigator’s Choice of Therapy in Participants With Metastatic Castration-resistant Prostate Cancer
NCT07028853	PHASE3	RECRUITING	This Study Will Explore Whether a Combination of the Investigational Drug Mevrometostat (PF-06821497) and Enzalutamide Will Work Better Than Taking Enzalutamide Alone in Participants With mCSPC Who Are ARPI naïve.
NCT07241416	PHASE3	RECRUITING	A Phase III Clinical Study of Rezvilutamide in Patients With Metastatic Hormone-Sensitive Prostate Cancer
NCT07611110	PHASE3	RECRUITING	AZD2265 Compared With Standard of Care in PSMA-positive Metastatic Castration-resistant Prostate Cancer (VECTRA-01)
NCT00974311	PHASE3	COMPLETED	Safety and Efficacy Study of MDV3100 in Patients With Castration-Resistant Prostate Cancer Who Have Been Previously Treated With Docetaxel-based Chemotherapy
NCT01212991	PHASE3	COMPLETED	A Safety and Efficacy Study of Oral MDV3100 in Chemotherapy-Naive Patients With Progressive Metastatic Prostate Cancer
NCT01949337	PHASE3	UNKNOWN	Enzalutamide With or Without Abiraterone and Prednisone in Treating Patients With Castration-Resistant Metastatic Prostate Cancer
NCT02003924	PHASE3	COMPLETED	Safety and Efficacy Study of Enzalutamide in Patients With Nonmetastatic Castration-Resistant Prostate Cancer
NCT02288247	PHASE3	COMPLETED	A Study to Assess the Benefit of Treatment Beyond Progression With Enzalutamide in Men Who Are Starting Treatment With Docetaxel After Worsening of Their Prostate Cancer When Taking Enzalutamide Alone
NCT02294461	PHASE3	COMPLETED	An Asian Study to Evaluate Efficacy and Safety of Oral Enzalutamide in Progressive Metastatic Prostate Cancer Participants
NCT02438007	PHASE3	TERMINATED	A Study of Galeterone Compared to Enzalutamide In Men Expressing Androgen Receptor Splice Variant-7 mRNA (AR-V7) Metastatic CRPC
NCT02677896	PHASE3	COMPLETED	A Study of Enzalutamide Plus Androgen Deprivation Therapy (ADT) Versus Placebo Plus ADT in Patients With Metastatic Hormone Sensitive Prostate Cancer (mHSPC)
NCT02929576	PHASE3	WITHDRAWN	Efficacy and Safety Study of Enzalutamide in Combination With Paclitaxel Chemotherapy or as Monotherapy Versus Placebo With Paclitaxel in Patients With Advanced, Diagnostic-Positive, Triple-Negative Breast Cancer
NCT02987543	PHASE3	COMPLETED	Study of Olaparib (Lynparza™) Versus Enzalutamide or Abiraterone Acetate in Men With Metastatic Castration-Resistant Prostate Cancer (PROfound Study)
NCT03016312	PHASE3	COMPLETED	A Study of Atezolizumab (Anti-PD-L1 Antibody) in Combination With Enzalutamide in Participants With Metastatic Castration-Resistant Prostrate Cancer (mCRPC) After Failure of an Androgen Synthesis Inhibitor And Failure of, Ineligibility For, or Refusal of a Taxane Regimen
NCT03295565	PHASE2/PHASE3	COMPLETED	Optimal Sequencing of Treatment Options for Poor Risk mCRPC Previously Treated With Docetaxel
NCT03834519	PHASE3	COMPLETED	Study of Pembrolizumab (MK-3475) Plus Olaparib Versus Abiraterone Acetate or Enzalutamide in Metastatic Castration-resistant Prostate Cancer (mCRPC) (MK-7339-010/KEYLYNK-010)
NCT03850795	PHASE3	TERMINATED	HC-1119 Versus Enzalutamide in Metastatic Castration-Resistant Prostate Cancer (mCRPC)
NCT04191096	PHASE3	COMPLETED	Efficacy and Safety of Pembrolizumab (MK-3475) Plus Enzalutamide Plus Androgen Deprivation Therapy (ADT) Versus Placebo Plus Enzalutamide Plus ADT in Participants With Metastatic Hormone-Sensitive Prostate Cancer (mHSPC) (MK-3475-991/KEYNOTE-991)
NCT04237584	PHASE3	TERMINATED	A Study Comparing ARB With Radium-223 vs ARB Therapy With Placebo and the Effect Upon Survival for mCRPC Patients
NCT04409288	PHASE3	TERMINATED	Patient Preference of Apalutamide Versus Enzalutamide in Patients With Recurrent or Metastatic Hormone-Sensitive Prostate Cancer
NCT04844749	PHASE3	TERMINATED	Efficacy Evaluation of VERU-111 for mCRPC in Patients Who Have Failed at Least One Androgen Receptor Targeting Agent
NCT04934722	PHASE3	COMPLETED	Efficacy and Safety of Pembrolizumab (MK-3475) Plus Enzalutamide Plus Androgen Deprivation Therapy (ADT) Versus Placebo Plus Enzalutamide Plus ADT in Participants With Metastatic Hormone-Sensitive Prostate Cancer (mHSPC) (MK-3475-991/KEYNOTE-991)-China Extension
NCT05627752	PHASE2/PHASE3	UNKNOWN	Docetaxel Alone or in Combination With Enzalutamide for mCRPC Previously Treated With Abiraterone at mHSPC Stage
NCT01990196	PHASE2	ACTIVE_NOT_RECRUITING	Neoadjuvant Phase 2 Study Comparing the Effects of AR Inhibition With/Without SRC or MEK Inhibition in Prostate Cancer
NCT02312557	PHASE2	ACTIVE_NOT_RECRUITING	Pembrolizumab in Treating Patients With Metastatic Castration Resistant Prostate Cancer Previously Treated With Enzalutamide
NCT02452008	PHASE2	ACTIVE_NOT_RECRUITING	Study of TGF-β Receptor Inhibitor Galunisertib (LY2157299) and Enzalutamide in Metastatic Castration-resistant Prostate Cancer
NCT02522715	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Enzalutamide and Cabazitaxel in Treating Patients With Metastatic, Castration-Resistant Prostate Cancer
NCT02749903	PHASE2	ACTIVE_NOT_RECRUITING	Enzalutamide for Patients With Androgen Receptor Positive Salivary Cancers
NCT02750358	PHASE2	ACTIVE_NOT_RECRUITING	Feasibility Study of Adjuvant Enzalutamide for the Treatment of Early Stage AR (+) Triple Negative Breast Cancer
NCT02861573	PHASE1/PHASE2	RECRUITING	Study of Pembrolizumab (MK-3475) Combination Therapies in Metastatic Castration-Resistant Prostate Cancer (MK-3475-365/KEYNOTE-365)
NCT02955394	PHASE2	ACTIVE_NOT_RECRUITING	Preoperative Fulvestrant With or Without Enzalutamide in ER+/Her2- Breast Cancer
NCT02960022	PHASE2	RECRUITING	A Study for Subjects With Prostate Cancer Who Previously Participated in an Enzalutamide Clinical Study
NCT03246347	PHASE2	ACTIVE_NOT_RECRUITING	A Trial of Androgen Deprivation, Docetaxel, and Enzalutamide for Metastatic Prostate Cancer
NCT03344211	PHASE2	ACTIVE_NOT_RECRUITING	Enzalutamide With or Without Radium Ra 223 Dichloride in Patients With Metastatic, Castration-Resistant Prostate Cancer
NCT03753243	PHASE2	RECRUITING	Neoadjuvant Pembrolizumab Plus Androgen Axis Blockade Prior to Prostatectomy for High Risk Localized Prostate Cancer
NCT03809000	PHASE2	ACTIVE_NOT_RECRUITING	A Study of Salvage Radiotherapy With or Without Enzalutamide in Recurrent Prostate Cancer Following Surgery
NCT03899155	PHASE2	RECRUITING	Pan Tumor Rollover Study
NCT04015622	PHASE2	ACTIVE_NOT_RECRUITING	PROstate Cancer TReatment Optimization Via Analysis of Circulating Tumour DNA
NCT04104776	PHASE1/PHASE2	RECRUITING	A Study of Tulmimetostat DZR123 (CPI-0209) in Patients With Advanced Solid Tumors and Lymphomas
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NCT04262154	PHASE2	ACTIVE_NOT_RECRUITING	Study of Abiraterone Acetate or Enzalutamide, Atezolizumab, GnRH Analog and Radiation Therapy in Men With Newly Diagnosed Hormone-sensitive Prostate Cancer
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Clinical evidence (CIViC)

Variant × indication × effect (13 predictive associations from 19 curated evidence items):

Variant	Indication	Effect	Therapy	Level	CIViC
ATR Loss-of-function	Castration-resistant Prostate Carcinoma	Sensitivity/Response	Talazoparib + Enzalutamide	CIViC A	EID12217
BRCA1 Mutation	Castration-resistant Prostate Carcinoma	Sensitivity/Response	Talazoparib + Enzalutamide	CIViC A	EID11734
BRCA2 Mutation	Castration-resistant Prostate Carcinoma	Sensitivity/Response	Talazoparib + Enzalutamide	CIViC A	EID11733
CDK12 Mutation	Castration-resistant Prostate Carcinoma	Sensitivity/Response	Talazoparib + Enzalutamide	CIViC A	EID11735
AR AR-V7	Prostate Cancer	Sensitivity/Response	Galeterone + Enzalutamide	CIViC B	EID9549
ATM Mutation	Castration-resistant Prostate Carcinoma	Sensitivity/Response	Enzalutamide + Talazoparib	CIViC B	EID11736
CHEK2 mutation	Castration-resistant Prostate Carcinoma	Sensitivity/Response	Enzalutamide + Talazoparib	CIViC B	EID11737
AR AR-V7	Prostate Cancer	Resistance	Abiraterone + Enzalutamide	CIViC B	EID12463 +5
AR AR-V7	Prostate Cancer	Resistance	Enzalutamide + Abiraterone	CIViC B	EID12464 +1
AR AR alternative transcripts	Prostate Cancer	Resistance	Abiraterone + Enzalutamide	CIViC B	EID9578
AR AR-V7	Prostate Cancer	Resistance	Enzalutamide	CIViC B	EID9554
PTEN Mutation	Prostate Adenocarcinoma	Sensitivity/Response	PI3Kbeta Inhibitor AZD8186 + Enzalutamide + Alpelisib	CIViC D	EID1522
AR F877L	Prostate Cancer	Resistance	Enzalutamide + Apalutamide	CIViC D	EID447

Pharmacology

Pharmacogenomics

No CPIC/DPWG dosing guideline or drug-level clinical/variant annotations in PharmGKB for this molecule.

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 100 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
DAROLUTAMIDE	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
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
PRANLUKAST	ChEMBL	Phase 4 (approved)	AR
PRASUGREL	ChEMBL	Phase 4 (approved)	AR
PREDNISOLONE	ChEMBL	Phase 4 (approved)	AR
PROGESTERONE	ChEMBL	Phase 4 (approved)	AR
PYRVINIUM	ChEMBL	Phase 4 (approved)	AR
RIFAPENTINE	ChEMBL	Phase 4 (approved)	AR
SERTACONAZOLE	ChEMBL	Phase 4 (approved)	AR
SPIRONOLACTONE	ChEMBL	Phase 4 (approved)	AR
STIRIPENTOL	ChEMBL	Phase 4 (approved)	AR
TESTOSTERONE	ChEMBL	Phase 4 (approved)	AR
TESTOSTERONE PROPIONATE	ChEMBL	Phase 4 (approved)	AR
TRETINOIN	ChEMBL	Phase 4 (approved)	AR
TROGLITAZONE	ChEMBL	Phase 4 (approved)	AR
ULIPRISTAL	ChEMBL	Phase 4 (approved)	AR
ASOPRISNIL	ChEMBL	Phase 3	AR
CYPROTERONE	ChEMBL	Phase 3	AR
ENOBOSARM	ChEMBL	Phase 3	AR
ETHISTERONE	ChEMBL	Phase 3	AR
GALETERONE	ChEMBL	Phase 3	AR
GESTODENE	ChEMBL	Phase 3	AR
GOSSYPOL	ChEMBL	Phase 3	AR
TIRATRICOL	ChEMBL	Phase 3	AR
TIRILAZAD	ChEMBL	Phase 3	AR
ALLYLESTRENOL	ChEMBL	Phase 2	AR
BENTAZEPAM	ChEMBL	Phase 2	AR
CIFENLINE	ChEMBL	Phase 2	AR
CLOFOCTOL	ChEMBL	Phase 2	AR
DICHLORISONE	ChEMBL	Phase 2	AR
DIOXYBENZONE	ChEMBL	Phase 2	AR
FLAVONE	ChEMBL	Phase 2	AR
FLUMETHASONE	ChEMBL	Phase 2	AR
FLUOCORTIN BUTYL	ChEMBL	Phase 2	AR
GUMELUTAMIDE	ChEMBL	Phase 2	AR
HALOMETASONE	ChEMBL	Phase 2	AR
HYDROCORTISONE ACEPONATE	ChEMBL	Phase 2	AR
HYDROXYFLUTAMIDE	ChEMBL	Phase 2	AR
LONAPRISAN	ChEMBL	Phase 2	AR
METRIBOLONE	ChEMBL	Phase 2	AR
MK-0773	ChEMBL	Phase 2	AR
ONAPRISTONE	ChEMBL	Phase 2	AR