Identification

Name
Rucaparib
Accession Number
DB12332
Type
Small Molecule
Groups
Approved, Investigational
Description

Rucaparib is a poly (ADP-ribose) polymerase (PARP) inhibitor approved (accelerated ) in December 2016 for the treatment of patients with deleterious BRCA mutation (germline and/or somatic) associated advanced ovarian cancer who have been treated with two or more chemotherapies.

Structure
Thumb
Synonyms
Not Available
External IDs
AG-14447
Product Ingredients
IngredientUNIICASInChI Key
Rucaparib camsylate41AX9SJ8KO1859053-21-6INBJJAFXHQQSRW-STOWLHSFSA-N
Rucaparib phosphateH3M9955244459868-92-9FCCGJTKEKXUBFZ-UHFFFAOYSA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
RubracaTablet, film coated200 mg/1OralClovis Oncology, Inc.2016-12-19Not applicableUs
RubracaTablet, film coated300 mg/1OralClovis Oncology, Inc.2016-12-19Not applicableUs
RubracaTablet, film coated250 mg/1OralClovis Oncology, Inc.2017-05-01Not applicableUs
Categories
UNII
8237F3U7EH
CAS number
283173-50-2
Weight
Average: 323.371
Monoisotopic: 323.143390375
Chemical Formula
C19H18FN3O
InChI Key
HMABYWSNWIZPAG-UHFFFAOYSA-N
InChI
InChI=1S/C19H18FN3O/c1-21-10-11-2-4-12(5-3-11)18-14-6-7-22-19(24)15-8-13(20)9-16(23-18)17(14)15/h2-5,8-9,21,23H,6-7,10H2,1H3,(H,22,24)
IUPAC Name
6-fluoro-2-{4-[(methylamino)methyl]phenyl}-3,10-diazatricyclo[6.4.1.0^{4,13}]trideca-1,4,6,8(13)-tetraen-9-one
SMILES
CNCC1=CC=C(C=C1)C1=C2CCNC(=O)C3=C2C(N1)=CC(F)=C3

Pharmacology

Indication

treatment of ovarian cancer, specifically those with alterations in BRCA1 and BRCA2 genes in the tumor tissue of ovarian cancer.

Structured Indications
Pharmacodynamics

Cardiac Electrophysiology: The effect of multiple doses of rucaparib on QTc interval was evaluated in an open-label single-arm study in 56 patients with solid tumors who were administered continuous doses of rucaparib ranging from 40 mg once daily (0.03 times the approved recommended dosage) to 840 mg twice daily (1.4 times the approved recommended dosage). The mean QTcF increase from baseline (90% confidence interval [CI]) in population pharmacokinetics estimated 95% percentile Cmax (3019 ng/mL) at steady state of 600 mg rucaparib twice daily was 14.9 msec (11.1-18.7 msec)

Mechanism of action

Rucaparib is an inhibitor of poly (ADP-ribose) polymerase (PARP) enzymes, including PARP-1, PARP-2, and PARP-3, which play a role in DNA repair. In vitro studies have shown that rucaparib-induced cytotoxicity may involve inhibition of PARP enzymatic activity and increased formation of PARP-DNA complexes resulting in DNA damage, apoptosis, and cell death. Increased rucaparib-induced cytotoxicity was observed in tumor cell lines with deficiencies in BRCA1/2 and other DNA repair genes. Rucaparib has been shown to decrease tumor growth in mouse xenograft models of human cancer with or without deficiencies in BRCA. Rucaparib sensitise cancer cells to X-radiation or (131)I-meta-iodobenzylguanidine treatment. It is likely that the mechanism of radiosensitisation entails the accumulation of unrepaired radiation-induced DNA damage. The administration of PARP-1 inhibitors and (131)I-meta-iodobenzylguanidine to high risk neuroblastoma patients would be beneficial

TargetActionsOrganism
APoly [ADP-ribose] polymerase 1
antagonist
Human
APoly [ADP-ribose] polymerase 2
antagonist
Human
APoly [ADP-ribose] polymerase 3
antagonist
Human
Absorption

The median T max was 1.9 hours at the approved recommended dosage. The mean absolute bioavailability of rucaparib immediate-release tablet was 36% with a range from 30% to 45%. Following a high-fat meal, the Cmax was increased by 20% and AUC 0-24h was increased by 38%, and T max was delayed by 2.5 hours, as compared to dosing under fasted conditions

Volume of distribution

Rucaparib had a steady-state volume of distribution of 113 L to 262 L following a single intravenous dose of 12 mg to 40 mg rucaparib.

Protein binding

70%

Metabolism

In vitro, rucaparib was metabolized primarily by CYP2D6 and to a lesser extent by CYP1A2 and CYP3A4.

Route of elimination

Fecal excretion was the major route of elimination, accounting for ≥ 79% of the total dose.

Half life

The mean terminal T 1/2 of rucaparib was 17 to 19 hours, following a single oral dose of 600 mg rucaparib.

Clearance

The apparent clearance ranged from 15.3 to 79.2 L/hour, following continuous 600 mg rucaparib orally twice daily. The clearance ranged from 13.9 to 18.4 L/hour, following a single intravenous dose of rucaparib 12 mg to 40 mg.

Toxicity

Not Available

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
AbirateroneThe serum concentration of Rucaparib can be increased when it is combined with Abiraterone.Approved
AcetyldigitoxinAcetyldigitoxin may decrease the cardiotoxic activities of Rucaparib.Approved
AcetyldigoxinAcetyldigoxin may decrease the cardiotoxic activities of Rucaparib.Experimental
AmiodaroneThe metabolism of Rucaparib can be decreased when combined with Amiodarone.Approved, Investigational
AprepitantThe serum concentration of Rucaparib can be increased when it is combined with Aprepitant.Approved, Investigational
ArtemetherThe metabolism of Rucaparib can be decreased when combined with Artemether.Approved
AtazanavirThe metabolism of Rucaparib can be decreased when combined with Atazanavir.Approved, Investigational
AtomoxetineThe metabolism of Rucaparib can be decreased when combined with Atomoxetine.Approved
AzithromycinThe metabolism of Rucaparib can be decreased when combined with Azithromycin.Approved
BetaxololThe metabolism of Rucaparib can be decreased when combined with Betaxolol.Approved
BevacizumabBevacizumab may increase the cardiotoxic activities of Rucaparib.Approved, Investigational
BoceprevirThe metabolism of Rucaparib can be decreased when combined with Boceprevir.Approved, Withdrawn
BortezomibThe metabolism of Rucaparib can be decreased when combined with Bortezomib.Approved, Investigational
BosentanThe serum concentration of Rucaparib can be decreased when it is combined with Bosentan.Approved, Investigational
BupropionThe metabolism of Rucaparib can be decreased when combined with Bupropion.Approved
CabazitaxelThe risk or severity of adverse effects can be increased when Cabazitaxel is combined with Rucaparib.Approved
CaffeineThe metabolism of Rucaparib can be decreased when combined with Caffeine.Approved
CarbamazepineThe metabolism of Rucaparib can be increased when combined with Carbamazepine.Approved, Investigational
CelecoxibThe metabolism of Rucaparib can be decreased when combined with Celecoxib.Approved, Investigational
CeritinibThe serum concentration of Rucaparib can be increased when it is combined with Ceritinib.Approved
ChloroquineThe metabolism of Rucaparib can be decreased when combined with Chloroquine.Approved, Vet Approved
ChlorpromazineThe metabolism of Rucaparib can be decreased when combined with Chlorpromazine.Approved, Vet Approved
CholecalciferolThe metabolism of Rucaparib can be decreased when combined with Cholecalciferol.Approved, Nutraceutical
CimetidineThe metabolism of Rucaparib can be decreased when combined with Cimetidine.Approved
CinacalcetThe metabolism of Rucaparib can be decreased when combined with Cinacalcet.Approved
CitalopramThe metabolism of Rucaparib can be decreased when combined with Citalopram.Approved
ClarithromycinThe metabolism of Rucaparib can be decreased when combined with Clarithromycin.Approved
ClemastineThe metabolism of Rucaparib can be decreased when combined with Clemastine.Approved
ClobazamThe metabolism of Rucaparib can be decreased when combined with Clobazam.Approved, Illicit
ClomipramineThe metabolism of Rucaparib can be decreased when combined with Clomipramine.Approved, Vet Approved
ClotrimazoleThe metabolism of Rucaparib can be decreased when combined with Clotrimazole.Approved, Vet Approved
ClozapineThe metabolism of Rucaparib can be decreased when combined with Clozapine.Approved
CobicistatThe serum concentration of Rucaparib can be increased when it is combined with Cobicistat.Approved
CocaineThe metabolism of Rucaparib can be decreased when combined with Cocaine.Approved, Illicit
ConivaptanThe serum concentration of Rucaparib can be increased when it is combined with Conivaptan.Approved, Investigational
CrizotinibThe metabolism of Rucaparib can be decreased when combined with Crizotinib.Approved
CyclophosphamideCyclophosphamide may increase the cardiotoxic activities of Rucaparib.Approved, Investigational
CyclosporineThe metabolism of Rucaparib can be decreased when combined with Cyclosporine.Approved, Investigational, Vet Approved
CymarinCymarin may decrease the cardiotoxic activities of Rucaparib.Experimental
Cyproterone acetateThe serum concentration of Rucaparib can be decreased when it is combined with Cyproterone acetate.Approved, Investigational
DabrafenibThe serum concentration of Rucaparib can be decreased when it is combined with Dabrafenib.Approved
DarifenacinThe metabolism of Rucaparib can be decreased when combined with Darifenacin.Approved, Investigational
DarunavirThe serum concentration of Rucaparib can be increased when it is combined with Darunavir.Approved
DasatinibThe serum concentration of Rucaparib can be increased when it is combined with Dasatinib.Approved, Investigational
DeferasiroxThe serum concentration of Rucaparib can be decreased when it is combined with Deferasirox.Approved, Investigational
DelavirdineThe metabolism of Rucaparib can be decreased when combined with Delavirdine.Approved
DesipramineThe metabolism of Rucaparib can be decreased when combined with Desipramine.Approved
DeslanosideDeslanoside may decrease the cardiotoxic activities of Rucaparib.Approved
DigitoxinDigitoxin may decrease the cardiotoxic activities of Rucaparib.Approved, Investigational
DigoxinDigoxin may decrease the cardiotoxic activities of Rucaparib.Approved
Digoxin Immune Fab (Ovine)Digoxin Immune Fab (Ovine) may decrease the cardiotoxic activities of Rucaparib.Approved
DihydroergotamineThe metabolism of Rucaparib can be decreased when combined with Dihydroergotamine.Approved
DiltiazemThe metabolism of Rucaparib can be decreased when combined with Diltiazem.Approved
DiphenhydramineThe metabolism of Rucaparib can be decreased when combined with Diphenhydramine.Approved
DocetaxelThe risk or severity of adverse effects can be increased when Docetaxel is combined with Rucaparib.Approved, Investigational
DosulepinThe metabolism of Rucaparib can be decreased when combined with Dosulepin.Approved
DoxycyclineThe metabolism of Rucaparib can be decreased when combined with Doxycycline.Approved, Investigational, Vet Approved
DronedaroneThe metabolism of Rucaparib can be decreased when combined with Dronedarone.Approved
DuloxetineThe metabolism of Rucaparib can be decreased when combined with Duloxetine.Approved
EliglustatThe metabolism of Rucaparib can be decreased when combined with Eliglustat.Approved
EnzalutamideThe serum concentration of Rucaparib can be decreased when it is combined with Enzalutamide.Approved
ErythromycinThe metabolism of Rucaparib can be decreased when combined with Erythromycin.Approved, Vet Approved
FluconazoleThe metabolism of Rucaparib can be decreased when combined with Fluconazole.Approved
FluoxetineThe metabolism of Rucaparib can be decreased when combined with Fluoxetine.Approved, Vet Approved
FluvoxamineThe metabolism of Rucaparib can be decreased when combined with Fluvoxamine.Approved, Investigational
FosamprenavirThe metabolism of Rucaparib can be decreased when combined with Fosamprenavir.Approved
FosaprepitantThe serum concentration of Rucaparib can be increased when it is combined with Fosaprepitant.Approved
FosphenytoinThe metabolism of Rucaparib can be increased when combined with Fosphenytoin.Approved
Fusidic AcidThe serum concentration of Rucaparib can be increased when it is combined with Fusidic Acid.Approved
GitoformateGitoformate may decrease the cardiotoxic activities of Rucaparib.Experimental
HaloperidolThe metabolism of Rucaparib can be decreased when combined with Haloperidol.Approved
IdelalisibThe serum concentration of Rucaparib can be increased when it is combined with Idelalisib.Approved
ImatinibThe metabolism of Rucaparib can be decreased when combined with Imatinib.Approved
ImipramineThe metabolism of Rucaparib can be decreased when combined with Imipramine.Approved
IndinavirThe metabolism of Rucaparib can be decreased when combined with Indinavir.Approved
IsavuconazoniumThe metabolism of Rucaparib can be decreased when combined with Isavuconazonium.Approved, Investigational
IsoniazidThe metabolism of Rucaparib can be decreased when combined with Isoniazid.Approved
IsradipineThe metabolism of Rucaparib can be decreased when combined with Isradipine.Approved
ItraconazoleThe metabolism of Rucaparib can be decreased when combined with Itraconazole.Approved, Investigational
IvacaftorThe serum concentration of Rucaparib can be increased when it is combined with Ivacaftor.Approved
KetoconazoleThe metabolism of Rucaparib can be decreased when combined with Ketoconazole.Approved, Investigational
Lanatoside CLanatoside C may decrease the cardiotoxic activities of Rucaparib.Experimental
LidocaineThe metabolism of Rucaparib can be decreased when combined with Lidocaine.Approved, Vet Approved
LobeglitazoneThe metabolism of Rucaparib can be decreased when combined with Lobeglitazone.Approved, Investigational
LopinavirThe metabolism of Rucaparib can be decreased when combined with Lopinavir.Approved
LorcaserinThe metabolism of Rucaparib can be decreased when combined with Lorcaserin.Approved
LovastatinThe metabolism of Rucaparib can be decreased when combined with Lovastatin.Approved, Investigational
LuliconazoleThe serum concentration of Rucaparib can be increased when it is combined with Luliconazole.Approved
LumacaftorThe metabolism of Rucaparib can be increased when combined with Lumacaftor.Approved
LumefantrineThe metabolism of Rucaparib can be decreased when combined with Lumefantrine.Approved
ManidipineThe metabolism of Rucaparib can be decreased when combined with Manidipine.Approved, Investigational
MethadoneThe metabolism of Rucaparib can be decreased when combined with Methadone.Approved
MethotrimeprazineThe metabolism of Rucaparib can be decreased when combined with Methotrimeprazine.Approved
MetildigoxinMetildigoxin may decrease the cardiotoxic activities of Rucaparib.Experimental
MetoprololThe metabolism of Rucaparib can be decreased when combined with Metoprolol.Approved, Investigational
MexiletineThe metabolism of Rucaparib can be decreased when combined with Mexiletine.Approved
MidostaurinThe metabolism of Rucaparib can be decreased when combined with Midostaurin.Approved
MifepristoneThe serum concentration of Rucaparib can be increased when it is combined with Mifepristone.Approved, Investigational
MirabegronThe metabolism of Rucaparib can be decreased when combined with Mirabegron.Approved
MitotaneThe serum concentration of Rucaparib can be decreased when it is combined with Mitotane.Approved
NefazodoneThe metabolism of Rucaparib can be decreased when combined with Nefazodone.Approved, Withdrawn
NelfinavirThe metabolism of Rucaparib can be decreased when combined with Nelfinavir.Approved
NetupitantThe serum concentration of Rucaparib can be increased when it is combined with Netupitant.Approved
NevirapineThe metabolism of Rucaparib can be increased when combined with Nevirapine.Approved
NicardipineThe metabolism of Rucaparib can be decreased when combined with Nicardipine.Approved
NilotinibThe metabolism of Rucaparib can be decreased when combined with Nilotinib.Approved, Investigational
OlaparibThe metabolism of Rucaparib can be decreased when combined with Olaparib.Approved
OleandrinOleandrin may decrease the cardiotoxic activities of Rucaparib.Experimental, Investigational
OsimertinibThe serum concentration of Rucaparib can be increased when it is combined with Osimertinib.Approved
OuabainOuabain may decrease the cardiotoxic activities of Rucaparib.Approved
PaclitaxelThe risk or severity of adverse effects can be increased when Paclitaxel is combined with Rucaparib.Approved, Vet Approved
PalbociclibThe serum concentration of Rucaparib can be increased when it is combined with Palbociclib.Approved
PanobinostatThe serum concentration of Rucaparib can be increased when it is combined with Panobinostat.Approved, Investigational
ParoxetineThe metabolism of Rucaparib can be decreased when combined with Paroxetine.Approved, Investigational
Peginterferon alfa-2bThe serum concentration of Rucaparib can be decreased when it is combined with Peginterferon alfa-2b.Approved
PentobarbitalThe metabolism of Rucaparib can be increased when combined with Pentobarbital.Approved, Vet Approved
PeruvosidePeruvoside may decrease the cardiotoxic activities of Rucaparib.Experimental
PhenobarbitalThe metabolism of Rucaparib can be increased when combined with Phenobarbital.Approved
PhenytoinThe metabolism of Rucaparib can be increased when combined with Phenytoin.Approved, Vet Approved
PosaconazoleThe metabolism of Rucaparib can be decreased when combined with Posaconazole.Approved, Investigational, Vet Approved
PrimidoneThe metabolism of Rucaparib can be increased when combined with Primidone.Approved, Vet Approved
PromazineThe metabolism of Rucaparib can be decreased when combined with Promazine.Approved, Vet Approved
ProscillaridinProscillaridin may decrease the cardiotoxic activities of Rucaparib.Experimental
QuinidineThe metabolism of Rucaparib can be decreased when combined with Quinidine.Approved
QuinineThe metabolism of Rucaparib can be decreased when combined with Quinine.Approved
RanolazineThe metabolism of Rucaparib can be decreased when combined with Ranolazine.Approved, Investigational
RifabutinThe metabolism of Rucaparib can be increased when combined with Rifabutin.Approved
RifampicinThe metabolism of Rucaparib can be increased when combined with Rifampicin.Approved
RifapentineThe metabolism of Rucaparib can be increased when combined with Rifapentine.Approved
RitonavirThe metabolism of Rucaparib can be decreased when combined with Ritonavir.Approved, Investigational
RolapitantThe metabolism of Rucaparib can be decreased when combined with Rolapitant.Approved
RopiniroleThe metabolism of Rucaparib can be decreased when combined with Ropinirole.Approved, Investigational
SaquinavirThe metabolism of Rucaparib can be decreased when combined with Saquinavir.Approved, Investigational
SertralineThe metabolism of Rucaparib can be decreased when combined with Sertraline.Approved
SildenafilThe metabolism of Rucaparib can be decreased when combined with Sildenafil.Approved, Investigational
SiltuximabThe serum concentration of Rucaparib can be decreased when it is combined with Siltuximab.Approved
SimeprevirThe serum concentration of Rucaparib can be increased when it is combined with Simeprevir.Approved
St. John's WortThe serum concentration of Rucaparib can be decreased when it is combined with St. John's Wort.Investigational, Nutraceutical
StiripentolThe serum concentration of Rucaparib can be increased when it is combined with Stiripentol.Approved
SulfisoxazoleThe metabolism of Rucaparib can be decreased when combined with Sulfisoxazole.Approved, Vet Approved
TelaprevirThe metabolism of Rucaparib can be decreased when combined with Telaprevir.Approved, Withdrawn
TelithromycinThe metabolism of Rucaparib can be decreased when combined with Telithromycin.Approved
Tenofovir disoproxilThe metabolism of Rucaparib can be decreased when combined with Tenofovir disoproxil.Approved, Investigational
TerbinafineThe metabolism of Rucaparib can be decreased when combined with Terbinafine.Approved, Investigational, Vet Approved
TeriflunomideThe serum concentration of Rucaparib can be decreased when it is combined with Teriflunomide.Approved
TheophyllineThe metabolism of Rucaparib can be decreased when combined with Theophylline.Approved
ThioridazineThe metabolism of Rucaparib can be decreased when combined with Thioridazine.Approved, Withdrawn
TiclopidineThe metabolism of Rucaparib can be decreased when combined with Ticlopidine.Approved
TipranavirThe metabolism of Rucaparib can be decreased when combined with Tipranavir.Approved, Investigational
TocilizumabThe serum concentration of Rucaparib can be decreased when it is combined with Tocilizumab.Approved
TranylcypromineThe metabolism of Rucaparib can be decreased when combined with Tranylcypromine.Approved
TrastuzumabTrastuzumab may increase the cardiotoxic activities of Rucaparib.Approved, Investigational
VenlafaxineThe metabolism of Rucaparib can be decreased when combined with Venlafaxine.Approved
VerapamilThe metabolism of Rucaparib can be decreased when combined with Verapamil.Approved
VoriconazoleThe metabolism of Rucaparib can be decreased when combined with Voriconazole.Approved, Investigational
ZiprasidoneThe metabolism of Rucaparib can be decreased when combined with Ziprasidone.Approved
ZucapsaicinThe metabolism of Rucaparib can be decreased when combined with Zucapsaicin.Approved
Food Interactions
Not Available

References

General References
  1. Nile DL, Rae C, Hyndman IJ, Gaze MN, Mairs RJ: An evaluation in vitro of PARP-1 inhibitors, rucaparib and olaparib, as radiosensitisers for the treatment of neuroblastoma. BMC Cancer. 2016 Aug 11;16:621. doi: 10.1186/s12885-016-2656-8. [PubMed:27515310]
  2. Jenner ZB, Sood AK, Coleman RL: Evaluation of rucaparib and companion diagnostics in the PARP inhibitor landscape for recurrent ovarian cancer therapy. Future Oncol. 2016 Jun;12(12):1439-56. doi: 10.2217/fon-2016-0002. Epub 2016 Apr 18. [PubMed:27087632]
  3. Drew Y, Ledermann J, Hall G, Rea D, Glasspool R, Highley M, Jayson G, Sludden J, Murray J, Jamieson D, Halford S, Acton G, Backholer Z, Mangano R, Boddy A, Curtin N, Plummer R: Phase 2 multicentre trial investigating intermittent and continuous dosing schedules of the poly(ADP-ribose) polymerase inhibitor rucaparib in germline BRCA mutation carriers with advanced ovarian and breast cancer. Br J Cancer. 2016 Mar 29;114(7):723-30. doi: 10.1038/bjc.2016.41. Epub 2016 Mar 22. [PubMed:27002934]
  4. CENTER FOR DRUG EVALUATION AND RESEARCH [Link]
  5. Daily med. [Link]
  6. FDA Label [Link]
  7. wikipedia [Link]
External Links
KEGG Drug
D10079
PubChem Compound
9931954
PubChem Substance
347828593
ChemSpider
8107584
BindingDB
50446130
ChEBI
134689
ChEMBL
CHEMBL1173055
PharmGKB
PA166163418
HET
RPB
Wikipedia
Rucaparib
PDB Entries
4bjc / 4rv6

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1Active Not RecruitingOtherNeoplasms1
1CompletedTreatmentAdvanced Solid Tumors1
1Not Yet RecruitingTreatmentSolid Tumor, Unspecified, Adult1
1RecruitingOtherTumors, Solid1
1RecruitingTreatmentNeoplasms, Gynecologic1
1, 2Active Not RecruitingTreatmentAdvanced Solid Tumor With Evidence of Germline or Somatic BRCA / Cancer, Ovarian / Fallopian Tube Cancer / Malignant Peritoneal Neoplasm1
1, 2Not Yet RecruitingTreatmentAdenocarcinomas of the Gastroesophageal Junction / Biliary System Disorder / BRCA1 Gene Mutation / Brca2 Gene Mutation / Homologous Recombination Deficiency / PALB2 Gene Mutation / Pancreatic Adenocarcinoma Metastatic / Stage IV Colorectal Cancer AJCC v7 / Stage IV Pancreatic Cancer AJCC v6 and v7 / Stage IVA Colorectal Cancer AJCC v7 / Stage IVB Colorectal Cancer AJCC v71
2Active Not RecruitingTreatmentCancer, Breast1
2Active Not RecruitingTreatmentCancer, Ovarian / Fallopian Tube Cancer / Malignant Peritoneal Neoplasm / Ovarian Epithelial Cancer1
2CompletedTreatmentBrca1 Mutation Carrier / Brca2 Mutation Carrier / Cancer, Breast / Cancer, Ovarian1
2CompletedTreatmentMalignant Neoplasm of Pancreas / Pancreatic Ductal Adenocarcinoma1
2Not Yet RecruitingTreatmentProstate Cancer1
2RecruitingTreatmentMalignant Neoplasm of Pancreas1
2RecruitingTreatmentMetastatic Breast Cancer (MBC)1
2RecruitingTreatmentMetastatic Castration Resistant Prostate Cancer1
2WithdrawnTreatmentDiabetes Mellitus (DM) / Retinopathy, Diabetic1
3Active Not RecruitingTreatmentCancer, Ovarian / Fallopian Tube Cancer / Malignant Peritoneal Neoplasm1
3RecruitingTreatmentCancer, Ovarian / Fallopian Tube Cancer / Malignant Peritoneal Neoplasm / Ovarian Epithelial Cancer1
3RecruitingTreatmentMetastatic Castration Resistant Prostate Cancer1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
Tablet, film coatedOral200 mg/1
Tablet, film coatedOral250 mg/1
Tablet, film coatedOral300 mg/1
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US8859562No2011-08-042031-08-04Us
US8143241No2007-08-122027-08-12Us
US6495541No2000-01-102020-01-10Us
US8754072No2011-02-102031-02-10Us
US9045487No2011-02-102031-02-10Us
US8071579No2007-08-122027-08-12Us
US7531530No2004-07-232024-07-23Us
US7351701No2004-07-232024-07-23Us

Properties

State
Not Available
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0114 mg/mLALOGPS
logP2.39ALOGPS
logP2.45ChemAxon
logS-4.4ALOGPS
pKa (Strongest Acidic)13.16ChemAxon
pKa (Strongest Basic)9.32ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area56.92 Å2ChemAxon
Rotatable Bond Count3ChemAxon
Refractivity92.91 m3·mol-1ChemAxon
Polarizability35.19 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as 2-phenylindoles. These are indoles substituted at the 2-position with a phenyl group.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Indoles and derivatives
Sub Class
Indoles
Direct Parent
2-phenylindoles
Alternative Parents
Phenylpyrroles / Benzazepines / 3-alkylindoles / Phenylmethylamines / Benzylamines / Aralkylamines / Azepines / Aryl fluorides / Heteroaromatic compounds / Secondary carboxylic acid amides
show 9 more
Substituents
2-phenylindole / Benzazepine / 2-phenylpyrrole / 3-alkylindole / Benzylamine / Phenylmethylamine / Aralkylamine / Azepine / Benzenoid / Aryl fluoride
show 24 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
Zinc ion binding
Specific Function
Involved in the base excision repair (BER) pathway, by catalyzing the poly(ADP-ribosyl)ation of a limited number of acceptor proteins involved in chromatin architecture and in DNA metabolism. This ...
Gene Name
PARP1
Uniprot ID
P09874
Uniprot Name
Poly [ADP-ribose] polymerase 1
Molecular Weight
113082.945 Da
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
Nad+ adp-ribosyltransferase activity
Specific Function
Involved in the base excision repair (BER) pathway, by catalyzing the poly(ADP-ribosyl)ation of a limited number of acceptor proteins involved in chromatin architecture and in DNA metabolism. This ...
Gene Name
PARP2
Uniprot ID
Q9UGN5
Uniprot Name
Poly [ADP-ribose] polymerase 2
Molecular Weight
66205.31 Da
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
Nad+ adp-ribosyltransferase activity
Specific Function
Involved in the base excision repair (BER) pathway, by catalyzing the poly(ADP-ribosyl)ation of a limited number of acceptor proteins involved in chromatin architecture and in DNA metabolism. This ...
Gene Name
PARP3
Uniprot ID
Q9Y6F1
Uniprot Name
Poly [ADP-ribose] polymerase 3
Molecular Weight
60069.7 Da

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 Da
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Substrate
General Function
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP1A2
Uniprot ID
P05177
Uniprot Name
Cytochrome P450 1A2
Molecular Weight
58293.76 Da
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Substrate
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da

Drug created on October 20, 2016 15:59 / Updated on November 09, 2017 05:05