Apalutamide

Summary

Apalutamide (CHEMBL3183409) is an approved small molecule (ATC L02BB05) targeting AR; indicated across 8 conditions including prostate adenocarcinoma and prostate carcinoma; with CIViC clinical evidence for 1 variant-indication association (e.g. AR F877L in prostate cancer).

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: L02BB05
• Targets: 1 (AR)
• Indications: 8 conditions
• Clinical trials: 113
• Precision-oncology evidence (CIViC): 1 variant–indication association
• Chemistry: 477.4 Da · C21H15F4N5O2S

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL3183409
Name	Apalutamide
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	24872560
ATC	L02BB05
Molecular formula	C21H15F4N5O2S
Molecular weight	477.4
InChIKey	HJBWBFZLDZWPHF-UHFFFAOYSA-N

SMILES: CNC(=O)C1=C(C=C(C=C1)N2C(=S)N(C(=O)C23CCC3)C4=CC(=C(N=C4)C#N)C(F)(F)F)F

IUPAC name: 4-[7-[6-cyano-5-(trifluoromethyl)-3-pyridinyl]-8-oxo-6-sulfanylidene-5,7-diazaspiro[3.4]octan-5-yl]-2-fluoro-N-methylbenzamide

Also known as: Apalutamida, Apalutamide, Arn-509, ARN-509, Erleada, JNJ-56021927, SID174007290, APALUTAMIDE, Apatulamide

Parent form; salt/anhydrous children: CHEMBL4062002, CHEMBL4082191, CHEMBL4100200, CHEMBL4105484

Patent coverage: 1,661 distinct patent families (4,076 SureChEMBL compound mentions), from 3 matched compound structure(s). One matched structure accounts for 3,568 (88%) 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	6.7		P10275

Broader ChEMBL bioactivity targets: 3 (assay-derived). Sample: Androgen receptor, GABA-A receptor; anion channel, Androgen receptor.

Bioactivity

ChEMBL activities: 13 potent at pChembl ≥ 5 of 15 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
AR	7.8	IC50	16	nM	CHEMBL_ACT_19293358
AR	7.8	IC50	16	nM	CHEMBL_ACT_25828643
AR	7.79	IC50	16.25	nM	CHEMBL_ACT_18099852
AR	7.46	Ki	34.7	nM	CHEMBL_ACT_15634040
AR	7.03	Ki	93	nM	CHEMBL_ACT_22795674
AR	6.8	IC50	160	nM	CHEMBL_ACT_22432229
AR	6.7	IC50	200	nM	CHEMBL_ACT_22795676
AR	6.46	IC50	348.9	nM	CHEMBL_ACT_25932480
AR	5.84	Ki	1452	nM	CHEMBL_ACT_19293399
P15207	5.84	Ki	1452	nM	CHEMBL_ACT_22432274
GABRP	5.52	IC50	3000	nM	CHEMBL_ACT_24824308
AR	5.51	IC50	3110	nM	CHEMBL_ACT_26775440
AR	5.48	IC50	3280	nM	CHEMBL_ACT_26775434

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

8 indications (6 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 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
salivary gland cancer	2	MONDO:0004669	EFO:0003826
liver disorder	1	MONDO:0005154	EFO:0001421

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

Clinical trials

Total trials: 113.

Phase distribution

Phase	Trials
PHASE2	50
PHASE1	22
PHASE3	20
Not specified	16
PHASE4	2
PHASE1/PHASE2	2
PHASE2/PHASE3	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT04108208	PHASE4	ACTIVE_NOT_RECRUITING	A Study of Apalutamide in Chinese Participants With Non Metastatic Castration Resistant Prostate Cancer (NM-CRPC)
NCT04601441	PHASE4	UNKNOWN	Study to Evaluate ctDNA of mCSPC Patients Receiving Apalutamide in Japan
NCT01946204	PHASE3	ACTIVE_NOT_RECRUITING	A Study of Apalutamide (ARN-509) in Men With Non-Metastatic Castration-Resistant Prostate Cancer
NCT02257736	PHASE3	ACTIVE_NOT_RECRUITING	An Efficacy and Safety Study of Apalutamide (JNJ-56021927) in Combination With Abiraterone Acetate and Prednisone Versus Abiraterone Acetate and Prednisone in Participants With Chemotherapy-naive Metastatic Castration-resistant Prostate Cancer (mCRPC)
NCT02489318	PHASE3	ACTIVE_NOT_RECRUITING	A Study of Apalutamide (JNJ-56021927, ARN-509) Plus Androgen Deprivation Therapy (ADT) Versus ADT in Participants With mHSPC
NCT02531516	PHASE3	ACTIVE_NOT_RECRUITING	An Efficacy and Safety Study of JNJ-56021927 (Apalutamide) in High-risk Prostate Cancer Subjects Receiving Primary Radiation Therapy: ATLAS
NCT03767244	PHASE3	ACTIVE_NOT_RECRUITING	A Study of Apalutamide in Participants With High-Risk, Localized or Locally Advanced Prostate Cancer Who Are Candidates for Radical Prostatectomy
NCT03903835	PHASE3	RECRUITING	ProBio: A Biomarker Driven Study in Patients With Metastatic Prostate Cancer
NCT04134260	PHASE3	RECRUITING	Testing the Addition of the Drug Apalutamide to the Usual Hormone Therapy and Radiation Therapy After Surgery for Prostate Cancer, INNOVATE Trial
NCT04181203	PHASE3	ACTIVE_NOT_RECRUITING	Combined Apalutamide, Radiotherapy, and LHRH Agonist in Prostate Cancer Patients After Prostatectomy
NCT04423211	PHASE3	RECRUITING	Treating Prostate Cancer That Has Come Back After Surgery With Apalutamide and Targeted Radiation Based on PET Imaging
NCT04513717	PHASE3	ACTIVE_NOT_RECRUITING	Two Studies for Patients With High 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 High Gene Risk Score, The PREDICT-RT Trial
NCT04557059	PHASE3	ACTIVE_NOT_RECRUITING	A Study of Adding Apalutamide to Radiotherapy and LHRH Agonist in High-Risk Patients With Hormone-Sensitive Prostate Cancer
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
NCT05884398	PHASE3	ACTIVE_NOT_RECRUITING	A Study of an Intermittent ADT Approach With Apalutamide Monotherapy in Participants With mCSPC
NCT06274047	PHASE3	RECRUITING	PROSTATE-IQ: Parallel RandOmized STudy of Personalized Apalutamide Treatment and Evaluation to Improve Quality of Life in Post-Operative Radiation With Androgen Axis Suppression. A Phase III Multi-center Study for Men With Detectable PSA After Prostatectomy for Prostate Cancer.
NCT06592924	PHASE3	RECRUITING	Docetaxel to Androgen Receptor Pathway Inhibitors in Patients With Metastatic Castration Sensitive Prostate Cancer and Suboptimal PSA Response
NCT06931340	PHASE3	RECRUITING	Testing the Addition of Docetaxel (Chemotherapy) to the Usual Treatment (Hormonal Therapy and Apalutamide) for Metastatic Prostate Cancer, ASPIRE Trial
NCT07611110	PHASE3	RECRUITING	AZD2265 Compared With Standard of Care in PSMA-positive Metastatic Castration-resistant Prostate Cancer (VECTRA-01)
NCT03009981	PHASE3	COMPLETED	A Study of Androgen Annihilation in High-Risk Biochemically Relapsed Prostate Cancer
NCT03488810	PHASE3	WITHDRAWN	Apalutamide With Radiotherapy and Androgen Deprivation Therapy in Prostate Cancer
NCT03777982	PHASE3	TERMINATED	Conventional Androgen Deprivation Therapy (ADT) With or Without Abiraterone Acetate + Prednisone and Apalutamide Following a Detectable PSA After Radiation and ADT
NCT04409288	PHASE3	TERMINATED	Patient Preference of Apalutamide Versus Enzalutamide in Patients With Recurrent or Metastatic Hormone-Sensitive Prostate Cancer
NCT02703623	PHASE2	ACTIVE_NOT_RECRUITING	Abiraterone Acetate, Prednisone, and Apalutamide With or Without Ipilimumab or Cabazitaxel and Carboplatin in Treating Patients With Metastatic Castration-Resistant Prostate Cancer
NCT03080116	PHASE2	ACTIVE_NOT_RECRUITING	Neoadjuvant Degarelix With or Without Apalutamide (ARN-509) Followed by Radical Prostatectomy
NCT03141671	PHASE2	ACTIVE_NOT_RECRUITING	Randomized Phase II Study of Salvage XRT + ADT +/- Abiraterone and Apalutamide for Rising PSA After RP (FORMULA-509)
NCT03371719	PHASE2	ACTIVE_NOT_RECRUITING	Radiation Therapy With or Without Apalutamide in Treating Patients With Recurrent Prostate Cancer, the BALANCE Trial
NCT03412396	PHASE2	ACTIVE_NOT_RECRUITING	Apalutamide in Treating Patients With Prostate Cancer Before Radical Prostatectomy
NCT03436654	PHASE2	ACTIVE_NOT_RECRUITING	Multi-arm Multi-modality Therapy for Very High Risk Localized and Low Volume Metastatic Prostatic Adenocarcinoma
NCT03821792	PHASE2	ACTIVE_NOT_RECRUITING	Abiraterone Acetate, Prednisone, and Apalutamide in Treating Patients With Hormone-Naive Metastatic Prostate Cancer
NCT03902951	PHASE2	ACTIVE_NOT_RECRUITING	Antiandrogen Therapy and SBRT in Treating Patients With Recurrent, Metastatic Prostate Cancer
NCT04267887	PHASE2	ACTIVE_NOT_RECRUITING	Advanced ChemoHormonal Therapy for Treatment Naive Metastatic Prostate Cancer
NCT04325828	PHASE2	ACTIVE_NOT_RECRUITING	A Study of Apalutamide Combined With GnRH Agonist in Participants With Androgen Receptor Positive Salivary Gland Carcinoma
NCT04530552	PHASE2	ACTIVE_NOT_RECRUITING	Testing the Effects of Low Dose Apalutamide on Prostate-Specific Antigen (PSA) Levels in Men Scheduled for Removal of the Prostate Gland
NCT04947254	PHASE2	RECRUITING	Androgen Ablation Therapy With or Without Niraparib After Radiation Therapy for the Treatment of High-Risk Localized or Locally Advanced Prostate Cancer
NCT05159245	PHASE2	RECRUITING	The Finnish National Study to Facilitate Patient Access to Targeted Anti-cancer Drugs
NCT05367440	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Study of AZD5305 When Given in Combination With New Hormonal Agents in Patients With Metastatic Prostate Cancer
NCT05406999	PHASE2	RECRUITING	Neoadjuvant Intense Endocrine Therapy for High Risk and Locally Advanced Prostate Cancer
NCT05422911	PHASE2	NOT_YET_RECRUITING	Abiraterone, Enzalutamide, or Apalutamide in Castrate-sensitive Prostate Cancer.
NCT05534646	PHASE2	RECRUITING	Study of Apalutamide With Carotuximab in Metastatic, Castration-Resistant Prostate Cancer

Clinical evidence (CIViC)

Variant × indication × effect (1 predictive associations from 1 curated evidence items):

Variant	Indication	Effect	Therapy	Level	CIViC
AR F877L	Prostate Cancer	Resistance	Enzalutamide + Apalutamide	CIViC D	EID447

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
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
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