abiraterone acetate Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |

Stem definitionDrug idCAS RN
antiandrogens 4176 154229-18-2

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • abiraterone acetate
  • zytiga
  • CB-7630
  • CB7630
Abiraterone acetate is converted in vivo to abiraterone, an androgen biosynthesis inhibitor, that inhibits 17 alpha-hydroxylase/C17,20-lyase (CYP17). This enzyme is expressed in testicular, adrenal, and prostatic tumor tissues and is required for androgen biosynthesis. CYP17 catalyzes two sequential reactions: 1) the conversion of pregnenolone and progesterone to their 17alpha-hydroxy derivatives by 17alpha-hydroxylase activity and 2) the subsequent formation of dehydroepiandrosterone (DHEA) and androstenedione, respectively, by C17,20 lyase activity. DHEA and androstenedione are androgens and are precursors of testosterone. Inhibition of CYP17 by abiraterone can also result in increased mineralocorticoid production by the adrenals. Androgen sensitive prostatic carcinoma responds to treatment that decreases androgen levels. Androgen deprivation therapies, such as treatment with GnRH agonists or orchiectomy, decrease androgen production in the testes but do not affect androgen production by the adrenals or in the tumor. Abiraterone acetate decreased serum testosterone and other androgens in patients in the placebo-controlled clinical trial. It is not necessary to monitor the effect of abiraterone acetate on serum testosterone levels.
  • Molecular weight: 391.56
  • Formula: C26H33NO2
  • CLOGP: 6.11
  • LIPINSKI: 1
  • HAC: 3
  • HDO: 0
  • TPSA: 39.19
  • ALOGS: -5.59
  • ROTB: 3

  • Status: OFP

  • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

DoseUnitRoute
1 g O

ADMET properties:

None

Approvals:

DateAgencyCompanyOrphan
Sept. 5, 2011 EMA
April 28, 2011 FDA JANSSEN BIOTECH

FDA Adverse Event Reporting System (Female)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Prostatic specific antigen increased 50.00 41.55 4 62 0 46685996

FDA Adverse Event Reporting System (Male)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Prostatic specific antigen increased 1748.95 16.20 603 30772 11401 29909702
Death 1716.23 16.20 1969 29406 355314 29565789
Therapy cessation 716.70 16.20 339 31036 14798 29906305
Prostate cancer 668.87 16.20 376 30999 23581 29897522
Disease progression 648.25 16.20 589 30786 79285 29841818
Prostate cancer metastatic 646.75 16.20 231 31144 4836 29916267
Hot flush 601.99 16.20 298 31077 14382 29906721
Hospitalisation 374.82 16.20 335 31040 43984 29877119
Hypokalaemia 361.78 16.20 347 31028 49845 29871258
Metastases to bone 251.48 16.20 145 31230 9513 29911590
Osteonecrosis of jaw 244.42 16.20 182 31193 18436 29902667
Fatigue 238.05 16.20 805 30570 319868 29601235
Product size issue 169.33 16.20 50 31325 552 29920551
Urinary tract infection 140.94 16.20 266 31109 73393 29847710
Product use complaint 137.45 16.20 50 31325 1102 29920001
Hospice care 118.95 16.20 68 31307 4384 29916719
Adverse event 100.84 16.20 101 31274 15240 29905863
Toxicity to various agents 95.98 16.20 33 31342 177150 29743953
Incorrect dose administered 92.01 16.20 138 31237 31548 29889555
Prescribed underdose 88.92 16.20 70 31305 7689 29913414
Bone pain 84.58 16.20 102 31273 18924 29902179
Completed suicide 84.19 16.20 5 31370 99487 29821616
Product dose omission issue 83.77 16.20 248 31127 91383 29829720
Hypertension 65.45 16.20 276 31099 121078 29800025
Prostatic specific antigen abnormal 63.29 16.20 21 31354 348 29920755
Dysphagia 61.13 16.20 163 31212 56535 29864568
Decreased appetite 58.93 16.20 311 31064 149599 29771504
Hepatic function abnormal 52.92 16.20 128 31247 41817 29879286
Malignant neoplasm progression 52.63 16.20 181 31194 72106 29848997
Spinal cord compression 50.68 16.20 37 31338 3629 29917474
Oedema peripheral 49.68 16.20 231 31144 105601 29815502
Fluid retention 48.61 16.20 91 31284 24907 29896196
Urinary tract obstruction 48.55 16.20 35 31340 3366 29917737
Chemotherapy 48.34 16.20 19 31356 521 29920582
Hormone-refractory prostate cancer 47.85 16.20 20 31355 645 29920458
Muscular weakness 47.76 16.20 161 31214 63484 29857619
Blood potassium decreased 47.54 16.20 72 31303 16590 29904513
Pyrexia 46.49 16.20 156 31219 294333 29626770
Therapy change 44.62 16.20 30 31345 2579 29918524
Therapy interrupted 43.76 16.20 37 31338 4492 29916611
Acquired apparent mineralocorticoid excess 42.57 16.20 9 31366 19 29921084
Wrong technique in product usage process 42.46 16.20 98 31277 31057 29890046
Metastases to liver 41.90 16.20 57 31318 11908 29909195
Plasma cell myeloma 41.49 16.20 4 31371 53458 29867645
Blood alkaline phosphatase increased 39.61 16.20 96 31279 31391 29889712
Asthenia 38.99 16.20 378 30997 220912 29700191
Drug hypersensitivity 38.37 16.20 12 31363 68507 29852596
Liver function test abnormal 37.48 16.20 93 31282 30857 29890246
Back pain 36.98 16.20 208 31167 102388 29818715
Metastases to spine 36.32 16.20 25 31350 2233 29918870
Diabetes mellitus 35.08 16.20 110 31265 41755 29879348
Acute coronary syndrome 35.01 16.20 56 31319 13517 29907586
Oedema 34.24 16.20 111 31264 42882 29878221
Overdose 33.13 16.20 24 31351 84313 29836790
Haematuria 32.37 16.20 112 31263 44722 29876381
Cardiac failure 31.98 16.20 172 31203 83246 29837857
Prostate cancer stage IV 31.85 16.20 11 31364 207 29920896
Pruritus 31.39 16.20 47 31328 118157 29802946
Cystitis 31.01 16.20 41 31334 8333 29912770
Haemorrhage urinary tract 30.50 16.20 20 31355 1649 29919454
Acute biphenotypic leukaemia 30.45 16.20 8 31367 55 29921048
Hypotension 30.39 16.20 108 31267 200457 29720646
Blood urine present 29.98 16.20 44 31331 9856 29911247
Metastasis 29.94 16.20 26 31349 3272 29917831
Prostate cancer recurrent 29.93 16.20 15 31360 740 29920363
Acquired haemophilia 29.35 16.20 15 31360 772 29920331
Infusion related reaction 29.06 16.20 4 31371 40560 29880543
Prostatic specific antigen decreased 27.89 16.20 8 31367 79 29921024
Adverse drug reaction 27.45 16.20 69 31306 23076 29898027
Drug ineffective 27.34 16.20 504 30871 339883 29581220
Metabolic acidosis 26.13 16.20 4 31371 37457 29883646
Aggression 25.61 16.20 4 31371 36903 29884200
Peripheral swelling 25.51 16.20 129 31246 60945 29860158
Asthma 24.92 16.20 4 31371 36170 29884933
Liver disorder 24.81 16.20 78 31297 29644 29891459
Coma 24.66 16.20 6 31369 40443 29880660
Anxiety 24.57 16.20 35 31340 89836 29831267
Hydronephrosis 24.47 16.20 38 31337 8945 29912158
Neuropathy peripheral 24.04 16.20 23 31352 70452 29850651
Cardiac disorder 24.04 16.20 94 31281 39799 29881304
Intentional product misuse 23.51 16.20 4 31371 34663 29886440
Agitation 23.10 16.20 14 31361 54059 29867044
Condition aggravated 23.09 16.20 71 31304 137795 29783308
Suicidal ideation 22.73 16.20 5 31370 36109 29884994
Hepatotoxicity 22.47 16.20 55 31320 18090 29903013
Metastases to lung 22.35 16.20 34 31341 7861 29913242
Wheezing 22.28 16.20 3 31372 30935 29890168
Metastases to lymph nodes 22.20 16.20 24 31351 3953 29917150
Radiotherapy 22.03 16.20 10 31365 395 29920708
Constipation 21.89 16.20 197 31178 112709 29808394
Pelvic pain 21.82 16.20 18 31357 2111 29918992
Adrenal insufficiency 21.48 16.20 39 31336 10424 29910679
Coronary artery disease 21.06 16.20 13 31362 49699 29871404
Hypoxia 20.99 16.20 12 31363 47842 29873261
Acute kidney injury 20.87 16.20 185 31190 273657 29647446
White blood cell count increased 20.39 16.20 8 31367 39665 29881438
Cardio-respiratory arrest 20.38 16.20 18 31357 57288 29863815
Metastases to soft tissue 20.37 16.20 8 31367 219 29920884
Lactic acidosis 20.31 16.20 4 31371 31209 29889894
Neutropenia 20.26 16.20 68 31307 128472 29792631
Cardiac arrest 20.04 16.20 42 31333 92808 29828295
Transaminases increased 19.98 16.20 62 31313 23395 29897708
Fall 19.64 16.20 283 31092 181589 29739514
Injection site pain 19.48 16.20 4 31371 30306 29890797
Bradycardia 19.45 16.20 24 31351 65502 29855601
Febrile neutropenia 19.27 16.20 53 31322 106640 29814463
Hypersensitivity 19.17 16.20 17 31358 54011 29867092
Depressed level of consciousness 19.17 16.20 8 31367 38214 29882889
Blood creatinine increased 19.17 16.20 42 31333 91333 29829770
Haemorrhage subcutaneous 19.04 16.20 17 31358 2220 29918883
Fracture 18.63 16.20 27 31348 5979 29915124
Groin pain 18.60 16.20 24 31351 4762 29916341
Urosepsis 18.33 16.20 37 31338 10695 29910408
Mucosal inflammation 17.68 16.20 5 31370 30489 29890614
Apparent mineralocorticoid excess 17.68 16.20 4 31371 13 29921090
Free prostate-specific antigen increased 17.59 16.20 3 31372 0 29921103
Pollakiuria 17.59 16.20 48 31327 16858 29904245
Angioedema 17.56 16.20 7 31368 34377 29886726
Staphylococcal infection 17.44 16.20 5 31370 30219 29890884
Ophthalmic herpes zoster 17.30 16.20 10 31365 658 29920445
Hepatic enzyme increased 17.09 16.20 75 31300 33419 29887684
Investigation 16.85 16.20 11 31364 900 29920203
Respiratory arrest 16.59 16.20 5 31370 29253 29891850
Oxygen saturation decreased 16.23 16.20 13 31362 43427 29877676
Tachycardia 16.21 16.20 33 31342 73706 29847397

Pharmacologic Action:

SourceCodeDescription
ATC L02BX03 ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
ENDOCRINE THERAPY
HORMONE ANTAGONISTS AND RELATED AGENTS
Other hormone antagonists and related agents
MeSH PA D000970 Antineoplastic Agents
MeSH PA D065607 Cytochrome P-450 Enzyme Inhibitors
MeSH PA D004791 Enzyme Inhibitors
MeSH PA D006727 Hormone Antagonists
MeSH PA D065606 Metabolic Side Effects of Drugs and Substances
MeSH PA D065088 Steroid Synthesis Inhibitors
FDA MoA N0000182632 Cytochrome P450 17A1 Inhibitors
FDA EPC N0000182633 Cytochrome P450 17A1 Inhibitor
FDA MoA N0000182137 Cytochrome P450 2D6 Inhibitors
FDA MoA N0000187062 Cytochrome P450 2C8 Inhibitors
CHEBI has role CHEBI:35610 cytostatic
CHEBI has role CHEBI:50266 prodrugs
CHEBI has role CHEBI:68640 cyp17a1 inhibitors

Drug Use (View source of the data)

DiseaseRelationSNOMED_IDDOID
Malignant tumor of prostate indication 399068003 DOID:10283
Metastatic castration-resistant prostate cancer indication 427492003
Hyperbilirubinemia contraindication 14783006 DOID:2741
Hypertensive disorder contraindication 38341003 DOID:10763
Hypokalemia contraindication 43339004
Body fluid retention contraindication 43498006
Chronic heart failure contraindication 48447003
Liver function tests abnormal contraindication 166603001
Disease of liver contraindication 235856003 DOID:409
Pregnancy, function contraindication 289908002
Breastfeeding (mother) contraindication 413712001

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 3.68 Basic

Orange Book patent data (new drug applications)

None

Orange Book exclusivity data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRouteExclusivity dateDescription
250MG ZYTIGA JANSSEN BIOTECH N202379 April 28, 2011 RX TABLET ORAL Feb. 7, 2021 ABIRATERONE ACETATE IN COMBINULLTION WITH PREDNISONE FOR THE TREATMENT OF PATIENTS WITH METASTATIC HIGH-RISK CASTRATION-SENSITIVE PROSTATE CANCER
500MG ZYTIGA JANSSEN BIOTECH N202379 April 14, 2017 RX TABLET ORAL Feb. 7, 2021 ABIRATERONE ACETATE IN COMBINULLTION WITH PREDNISONE FOR THE TREATMENT OF PATIENTS WITH METASTATIC HIGH-RISK CASTRATION-SENSITIVE PROSTATE CANCER

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])
Mechanism
action
Bioact sourceMoA source
Steroid 17-alpha-hydroxylase/17,20 lyase Enzyme INHIBITOR IC50 8.54 CHEMBL IUPHAR
Cytochrome P450 3A4 Enzyme IC50 5.57 CHEMBL
Cytochrome P450 11B1, mitochondrial Enzyme IC50 5.79 CHEMBL
Cytochrome P450 11B2, mitochondrial Enzyme IC50 5.76 CHEMBL
Cytochrome P450 17A1 Enzyme IC50 7.90 CHEMBL

External reference:

IDSource
EM5OCB9YJ6 UNII
4030721 VUID
N0000182731 NUI
D09701 KEGG_DRUG
154229-19-3 SECONDARY_CAS_RN
4030720 VANDF
4030721 VANDF
C2607886 UMLSCUI
C0754011 UMLSCUI
CHEBI:68639 CHEBI
CHEBI:68642 CHEBI
AER PDB_CHEM_ID
CHEMBL271227 ChEMBL_ID
9821849 PUBCHEM_CID
CHEMBL254328 ChEMBL_ID
D000069501 MESH_DESCRIPTOR_UI
9288 IUPHAR_LIGAND_ID
C089740 MESH_SUPPLEMENTAL_RECORD_UI
7375 INN_ID
G819A456D0 UNII
132971 PUBCHEM_CID
6745 IUPHAR_LIGAND_ID
DB05812 DRUGBANK_ID
1100071 RXNORM
181225 MMSL
27860 MMSL
299803 MMSL
d07766 MMSL
013720 NDDF
013721 NDDF
699678007 SNOMEDCT_US
699679004 SNOMEDCT_US
767857007 SNOMEDCT_US

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
Abiraterone Acetate HUMAN PRESCRIPTION DRUG LABEL 1 0093-1125 TABLET, FILM COATED 250 mg ORAL ANDA 27 sections
Abiraterone HUMAN PRESCRIPTION DRUG LABEL 1 0143-9597 TABLET 250 mg ORAL ANDA 25 sections
Abiraterone Acetate HUMAN PRESCRIPTION DRUG LABEL 1 0378-6920 TABLET 250 mg ORAL ANDA 29 sections
Abiraterone Acetate HUMAN PRESCRIPTION DRUG LABEL 1 0378-6921 TABLET, FILM COATED 500 mg ORAL ANDA 29 sections
Abiraterone Acetate HUMAN PRESCRIPTION DRUG LABEL 1 0378-6924 TABLET, FILM COATED 250 mg ORAL ANDA 29 sections
Abiraterone Acetate HUMAN PRESCRIPTION DRUG LABEL 1 0904-6948 TABLET 250 mg ORAL ANDA 28 sections
Abiraterone Acetate HUMAN PRESCRIPTION DRUG LABEL 1 16714-963 TABLET 250 mg ORAL ANDA 27 sections
Abiraterone Acetate HUMAN PRESCRIPTION DRUG LABEL 1 42291-024 TABLET 250 mg ORAL ANDA 27 sections
ABIRATERONE ACETATE HUMAN PRESCRIPTION DRUG LABEL 1 42291-073 TABLET 500 mg ORAL ANDA 27 sections
Abiraterone Acetate HUMAN PRESCRIPTION DRUG LABEL 1 42292-057 TABLET 250 mg ORAL ANDA 29 sections
Abiraterone Acetate HUMAN PRESCRIPTION DRUG LABEL 1 43598-358 TABLET 250 mg ORAL ANDA 27 sections
YONSA HUMAN PRESCRIPTION DRUG LABEL 1 47335-401 TABLET 125 mg ORAL NDA 28 sections
Abiraterone Acetate HUMAN PRESCRIPTION DRUG LABEL 1 51407-181 TABLET 250 mg ORAL ANDA 29 sections
Zytiga HUMAN PRESCRIPTION DRUG LABEL 1 57894-150 TABLET 250 mg ORAL NDA 32 sections
Abiraterone acetate HUMAN PRESCRIPTION DRUG LABEL 1 57894-155 TABLET 250 mg ORAL NDA AUTHORIZED GENERIC 30 sections
Zytiga HUMAN PRESCRIPTION DRUG LABEL 1 57894-195 TABLET, FILM COATED 500 mg ORAL NDA 32 sections
Abiraterone acetate HUMAN PRESCRIPTION DRUG LABEL 1 57894-199 TABLET, FILM COATED 500 mg ORAL NDA 30 sections
Abiraterone Acetate HUMAN PRESCRIPTION DRUG LABEL 1 60505-4327 TABLET 250 mg ORAL ANDA 28 sections
Abiraterone Acetate HUMAN PRESCRIPTION DRUG LABEL 1 60687-455 TABLET 250 mg ORAL ANDA 29 sections
Abiraterone acetate HUMAN PRESCRIPTION DRUG LABEL 1 64679-021 TABLET 250 mg ORAL ANDA 26 sections
Abiraterone acetate Human Prescription Drug Label 1 64980-418 TABLET 250 mg ORAL ANDA 25 sections
Abiraterone HUMAN PRESCRIPTION DRUG LABEL 1 68001-489 TABLET 250 mg ORAL ANDA 25 sections
abiraterone acetate HUMAN PRESCRIPTION DRUG LABEL 1 68462-135 TABLET 250 mg ORAL ANDA 30 sections
Abiraterone Acetate HUMAN PRESCRIPTION DRUG LABEL 1 69238-1165 TABLET 250 mg ORAL ANDA 27 sections
ABIRATERONE ACETATE HUMAN PRESCRIPTION DRUG LABEL 1 69238-1754 TABLET 500 mg ORAL ANDA 27 sections
Abiraterone Human Prescription Drug Label 1 69539-049 TABLET 250 mg ORAL ANDA 25 sections
Abiraterone Human Prescription Drug Label 1 72205-030 TABLET 250 mg ORAL ANDA 25 sections
Abiraterone acetate HUMAN PRESCRIPTION DRUG LABEL 1 72606-566 TABLET 250 mg ORAL ANDA 31 sections