Rucaparib
Identification
- Summary
Rucaparib is an anti-cancer agent used to treat recurrent ovarian, fallopian tube, or peritoneal cancer.
- Brand Names
- Rubraca
- Generic Name
- Rucaparib
- DrugBank Accession Number
- DB12332
- Background
Rucaparib is a potent mammalian poly(ADP-ribose) polymerase (PARP) 1, 2 and 3 inhibitor with anticancer properties. PPAR is an enzyme that plays an essential role in DNA repair by activating response pathways and facilitating repair 2, and defects in these repair mechanisms have been demonstrated in various malignancies, including cancer. Regulation of repair pathways is critical in promoting necessary cell death. BRCA genes are tumor suppressor genes mediate several cellular process including DNA replication, transcription regulation, cell cycle checkpoints, apoptosis, chromatin structuring and homologous recombination (HR). Homologous recombination deficiency (HRD), along with PPAR inhibition, is a vulnerability that enhances the cell death pathway when the single mutations alone would permit viability. Ovarian cancer commonly possesses defects in DNA repair pathways such as HRD due to BRCA mutations or otherwise.
There are three main types of ovarian cancer: epithelial (90%), germ cell (5%) and sex cord stromal cell (5%). Epithelial ovarian, being the most common, fifth leading cause of cancer-related deaths in women in the United States. Advanced ovarian cancer particularly poses challenges due to reduced therapeutic response rates from standard platinum-based chemotherapy and overall survival rates. Rucaparib has shown to induce cytotoxicity in tumor cell lines with deficiencies in BRCA1/2 and other DNA repair genes Label. Of all the BRCA1/2 mutations in ovarian cancer, most are due to germline mutations (18%), and approximately 7% represent somatic mutations acquired within the tumor 4.
The indication of rucaparib as an oral monotherapy in patients with deleterious BRCA mutation (germline and/or somatic) associated advanced ovarian cancer was granted accelerated approval in 2016 for selected patients who have previously received greater than two lines of platinum-based therapy. It is currently marketed in the US under the brand name Rubraca that contains rucaparib camsylate as the active ingredient. The identification of patients who are eligible for rucaparib therapy is performed via in vitro diagnostic tests to detect the presence of a deleterious BRCA mutation (germline and/or somatic). The FDA-approved test qualitatively detects sequence alterations in BRCA1 and BRCA2 (BRCA1/2) genes. More information can be found on the FDA Website 8.
While rucaparib is indicated for deleterious BRCA mutation (germline and/or somatic)-associated advanced ovarian cancer, there is evidence that its antitumor activity is also clinically effective against ovarian tumors with high homologous recombination deficiency (HRD) loss of heterozygosity (LOH) 4.
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
Structure for Rucaparib (DB12332)
- Weight
- Average: 323.371
Monoisotopic: 323.143390375 - Chemical Formula
- C19H18FN3O
- Synonyms
- Rucaparib
- External IDs
- AG-14447
Pharmacology
- Indication
Indicated as monotherapy 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. Select patients for therapy based on an FDA-approved companion diagnostic for rucaparib.
Accelerate your drug discovery research with the industry’s only fully connected ADMET dataset, ideal for:Accelerate your drug discovery research with our fully connected ADMET dataset- Associated Conditions
- Contraindications & Blackbox Warnings
Contraindications & Blackbox WarningsWith our commercial data, access important information on dangerous risks, contraindications, and adverse effects.Our Blackbox Warnings cover Risks, Contraindications, and Adverse Effects- Pharmacodynamics
Rucaparib has been shown to decrease tumor growth in mouse xenograft models of human cancer with or without deficiencies in BRCA Label.
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) Label.
- Mechanism of action
Poly (ADP-ribose) polymerase (PARP) enzymes play a role in DNA repair. PPAR-1 is responsible in repairing single stranded breaks (SSBs) in base excision repair (BER). PARP1 also functions in nonhomologous end-joining (NHEJ) regulation, chromatin remodeling and homologous recombination (HR) DNA repair pathways 2. When PARP is inhibited, single-strand breaks become double-strand breaks, which are typically repaired via homologous recombination 2. Pre-existing homologous recombination deficiency (HRD) may occur through mutations in the BRCA1 or BRCA2 genes, which confers persistant cell repair and growth in cancer cells.
Rucaparib is an inhibitor of PARP-1, PARP-2, and PARP-3. Via an inhibitory effect on the PARP enzymatic activity, rucaparib decreases the formation of PARP-DNA complexes resulting in DNA damage, apoptosis, and cell death Label. It is proposed that PARP inhibition specifically targets tumor cells with preexisting HRD, such as those cells possessing mutations in the BRCA1 or BRCA2 genes 4. Rucaparib induces synthetic lethality by disrupting ingle- and double-strand repair pathways leading to tumor cell death. It is also suggested that PARP inhibition can lead to trapping of PARP-1 enzyme on damaged DNA, effectively preventing continuation of the DNA repair process; defective BRCA1 recruitment to damaged DNA; and activation of alternative DNA repair such as error-prone nonhomologous end joining (NHEJ) or alternative end joining pathways leading to mutations or chromosomal changes and ultimately cell death 4.
Target Actions Organism APoly [ADP-ribose] polymerase 1 antagonistHumans APoly [ADP-ribose] polymerase 2 antagonistHumans APoly [ADP-ribose] polymerase 3 antagonistHumans - Absorption
Rucaparib demonstrates a linear pharmacokinetic properties over a dose range from 240 to 840 mg twice daily with time-independence and dose-proportionality. The mean steady-state rucaparib Cmax was 1940 ng/mL (54% coefficient of variation [CV]) and AUC0-12h was 16900 h⋅ng/mL (54% CV) at the approved recommended dosage. The time to reach the steady-state peak plasma concentration (Tmax) was 1.9 hours at the 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 Label.
- Volume of distribution
Following a single intravenous dose of 12mg to 40mg rucaparib, the steady-state volume of distribution was 113L to 262L Label.
- Protein binding
In vitro, the protein binding of rucaparib was 70% in human plasma at therapeutic concentrations. Rucaparib preferentially distributed to red blood cells with a blood-to-plasma concentration ratio of 1.83 Label.
- Metabolism
According to in vitro studies, rucaparib is primarily metabolized by CYP2D6 and to a lesser extent by CYP1A2 and CYP3A4 Label.
- Route of elimination
Fecal excretion was the major route of elimination, accounting for ≥ 79% of the total dose.
- Half-life
Following a single oral dose of 600mg rucaparib, the mean terminal half life (t1/2) was 17-19 hours Label.
- Clearance
Following continuous 600mg rucaparib administration orally twice daily, the apparent clearance ranges from 15.3 to 79.2 L/hour. The clearance ranged from 13.9 to 18.4 L/hour, following a single intravenous dose of rucaparib 12 mg to 40 mg Label.
- Adverse Effects
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According to a bacterial reverse mutation (Ames) test, rucaparib has shown to be mutagenic. It was also clastogenic in an in vitro chromosomal aberration assay in cultured human lymphocytes. Rucaparib has a genotoxic potential. Based on its mechanism of action and findings from animal studies, rucaparib can cause fetal harm when administered to a pregnant woman. Female patients of reproductive potential should be advised to use effective contraception during treatment and for 6 months following the last dose of rucaparib Label.
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAbacavir The metabolism of Abacavir can be decreased when combined with Rucaparib. Abametapir The serum concentration of Rucaparib can be increased when it is combined with Abametapir. Abatacept The metabolism of Rucaparib can be increased when combined with Abatacept. Abemaciclib The metabolism of Abemaciclib can be decreased when combined with Rucaparib. Abiraterone The serum concentration of Rucaparib can be increased when it is combined with Abiraterone. Acalabrutinib The metabolism of Acalabrutinib can be decreased when combined with Rucaparib. Acebutolol The metabolism of Acebutolol can be decreased when combined with Rucaparib. Acenocoumarol The serum concentration of Acenocoumarol can be increased when it is combined with Rucaparib. Acetaminophen The metabolism of Acetaminophen can be decreased when combined with Rucaparib. Acetohexamide The metabolism of Acetohexamide can be decreased when combined with Rucaparib. 
Improve patient outcomesBuild effective decision support tools with the industry’s most comprehensive drug-drug interaction checker.Learn more - Food Interactions
- Exercise caution with grapefruit products. Rucaparib is primarily metabolized through CYP2D6 but is also metabolized by CYP3A4 and CYP1A2. Grapefruit inhibits CYP3A4 metabolism, which may increase rucaparib serum levels.
- Exercise caution with St. John's Wort. Rucaparib is primarily metabolized through CYP2D6 but is also metabolized by CYP3A4 and CYP1A2. St. John's Wort induces CYP3A4 metabolism, which may reduce rucaparib serum levels.
- Take with or without food. High-fat meals may increase the bioavailability and delay the Tmax of rucaparib.
Products
Comprehensive & structured drug product infoFrom application numbers to product codes, connect different identifiers through our commercial datasets.Easily connect various identifiers back to our datasets- Product Ingredients
Ingredient UNII CAS InChI Key Rucaparib camsylate 41AX9SJ8KO 1859053-21-6 INBJJAFXHQQSRW-STOWLHSFSA-N Rucaparib phosphate H3M9955244 459868-92-9 FCCGJTKEKXUBFZ-UHFFFAOYSA-N - Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Rubraca Tablet, film coated 200 mg Oral Clovis Oncology Ireland Limited 2020-12-16 Not applicable EU 
Rubraca Tablet, film coated 300 mg Oral Clovis Oncology Ireland Limited 2020-12-16 Not applicable EU Rubraca Tablet, film coated 200 mg/1 Oral Clovis Oncology, Inc. 2016-12-19 Not applicable US 
Rubraca Tablet, film coated 250 mg/1 Oral Clovis Oncology, Inc. 2017-05-01 Not applicable US Rubraca Tablet, film coated 250 mg Oral Clovis Oncology Ireland Limited 2020-12-16 Not applicable EU Rubraca Tablet, film coated 300 mg/1 Oral Clovis Oncology, Inc. 2016-12-19 Not applicable US
Categories
- ATC Codes
- L01XX55 — Rucaparib
- Drug Categories
- Antineoplastic Agents
- Antineoplastic and Immunomodulating Agents
- BCRP/ABCG2 Inhibitors
- BCRP/ABCG2 Substrates
- Cytochrome P-450 CYP1A2 Inducers
- Cytochrome P-450 CYP1A2 Inducers (moderate)
- Cytochrome P-450 CYP1A2 Inhibitors
- Cytochrome P-450 CYP1A2 Inhibitors (weak)
- Cytochrome P-450 CYP1A2 Substrates
- Cytochrome P-450 CYP1A2 Substrates with a Narrow Therapeutic Index
- Cytochrome P-450 CYP2C19 Inhibitors
- Cytochrome P-450 CYP2C19 Inhibitors (weak)
- Cytochrome P-450 CYP2C8 Inhibitors
- Cytochrome P-450 CYP2C8 Inhibitors (weak)
- Cytochrome P-450 CYP2C9 Inhibitors
- Cytochrome P-450 CYP2C9 Inhibitors (strength unknown)
- Cytochrome P-450 CYP2D6 Inhibitors
- Cytochrome P-450 CYP2D6 Inhibitors (moderate)
- Cytochrome P-450 CYP2D6 Substrates
- Cytochrome P-450 CYP2D6 Substrates with a Narrow Therapeutic Index
- Cytochrome P-450 CYP3A Inhibitors
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Inhibitors
- Cytochrome P-450 CYP3A4 Inhibitors (weak)
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 CYP3A4 Substrates with a Narrow Therapeutic Index
- Cytochrome P-450 CYP3A5 Inhibitors
- Cytochrome P-450 CYP3A5 Inhibitors (strength unknown)
- Cytochrome P-450 CYP3A7 Inhibitors
- Cytochrome P-450 CYP3A7 Inhibitors (strength unknown)
- Cytochrome P-450 Enzyme Inducers
- Cytochrome P-450 Enzyme Inhibitors
- Cytochrome P-450 Substrates
- Enzyme Inhibitors
- Heterocyclic Compounds, Fused-Ring
- MATE 1 Inhibitors
- MATE 2 Inhibitors
- MATE inhibitors
- Narrow Therapeutic Index Drugs
- OAT1/SLC22A6 inhibitors
- OAT3/SLC22A8 Inhibitors
- OATP1B1/SLCO1B1 Inhibitors
- OATP1B3 inhibitors
- OCT1 inhibitors
- P-glycoprotein inhibitors
- P-glycoprotein substrates
- P-glycoprotein substrates with a Narrow Therapeutic Index
- Poly(ADP-ribose) Polymerase Inhibitors
- UGT1A1 Inhibitors
- Chemical TaxonomyProvided by Classyfire
- 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 / 2-phenylpyrrole / 3-alkylindole / Amine / Amino acid or derivatives / Aralkylamine / Aromatic heteropolycyclic compound / Aryl fluoride / Aryl halide / Azacycle show 24 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- 8237F3U7EH
- CAS number
- 283173-50-2
- 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
References
- General References
- 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. [Article]
- 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. [Article]
- 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. [Article]
- Dockery LE, Gunderson CC, Moore KN: Rucaparib: the past, present, and future of a newly approved PARP inhibitor for ovarian cancer. Onco Targets Ther. 2017 Jun 19;10:3029-3037. doi: 10.2147/OTT.S114714. eCollection 2017. [Article]
- CENTER FOR DRUG EVALUATION AND RESEARCH [Link]
- Daily med. [Link]
- FDA Label [Link]
- FDA List of Cleared or Approved Companion Diagnostic Devices (In Vitro and Imaging Tools) [Link]
- External Links
- KEGG Drug
- D10079
- PubChem Compound
- 9931954
- PubChem Substance
- 347828593
- ChemSpider
- 8107584
- BindingDB
- 50446130
- 1862579
- ChEBI
- 134689
- ChEMBL
- CHEMBL1173055
- ZINC
- ZINC000000025958
- PharmGKB
- PA166163418
- PDBe Ligand
- RPB
- Wikipedia
- Rucaparib
- PDB Entries
- 4bjc / 4rv6 / 6vkk
- FDA label
- Download (344 KB)
Clinical Trials
- Clinical Trials
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Tablet, film coated Oral Tablet, film coated Oral 200 mg/1 Tablet, film coated Oral 200 mg Tablet, film coated Oral 250 mg Tablet, film coated Oral 250 mg/1 Tablet, film coated Oral 300 mg Tablet, film coated Oral 300 mg/1 - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US8859562 No 2014-10-14 2031-08-04 US US8143241 No 2012-03-27 2027-08-12 US US6495541 No 2002-12-17 2020-01-10 US US8754072 No 2014-06-17 2031-02-10 US US9045487 No 2015-06-02 2031-02-10 US US8071579 No 2011-12-06 2027-08-12 US US7531530 No 2009-05-12 2024-07-23 US US7351701 No 2008-04-01 2024-07-23 US US9861638 No 2018-01-09 2031-02-10 US US9987285 No 2018-06-05 2035-08-17 US US10130636 No 2018-11-20 2035-08-17 US US10278974 No 2019-05-07 2031-02-10 US
Properties
- State
- Solid
- Experimental Properties
Property Value Source water solubility 1 mg/mL FDA Label - Predicted Properties
Property Value Source Water Solubility 0.0114 mg/mL ALOGPS logP 2.39 ALOGPS logP 2.45 ChemAxon logS -4.4 ALOGPS pKa (Strongest Acidic) 13.16 ChemAxon pKa (Strongest Basic) 9.32 ChemAxon Physiological Charge 1 ChemAxon Hydrogen Acceptor Count 2 ChemAxon Hydrogen Donor Count 3 ChemAxon Polar Surface Area 56.92 Å2 ChemAxon Rotatable Bond Count 3 ChemAxon Refractivity 92.91 m3·mol-1 ChemAxon Polarizability 35.19 Å3 ChemAxon Number of Rings 4 ChemAxon Bioavailability 1 ChemAxon Rule of Five Yes ChemAxon Ghose Filter Yes ChemAxon Veber's Rule No ChemAxon MDDR-like Rule No ChemAxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS Not Available
Targets
- Kind
- Protein
- Organism
- Humans
- 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
- Humans
- 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
- Humans
- 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
- Humans
- Pharmacological action
- Yes
- Actions
- SubstrateInhibitor
- 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
- Humans
- Pharmacological action
- Yes
- Actions
- SubstrateInhibitorInducer
- Curator comments
- Inhibition of the enzyme is reversible.
- 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
References
- Dockery LE, Gunderson CC, Moore KN: Rucaparib: the past, present, and future of a newly approved PARP inhibitor for ovarian cancer. Onco Targets Ther. 2017 Jun 19;10:3029-3037. doi: 10.2147/OTT.S114714. eCollection 2017. [Article]
- Rucaparib - Drug Summary Prescribers Digital Reference [Link]
- Rupacarib [File]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- SubstrateInhibitorDownregulator
- 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
References
- Rucaparib - Drug Summary Prescribers Digital Reference [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- Curator comments
- Inhibition is reversible.
- General Function
- Oxygen binding
- 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
- CYP3A5
- Uniprot ID
- P20815
- Uniprot Name
- Cytochrome P450 3A5
- Molecular Weight
- 57108.065 Da
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- Curator comments
- Inhibition is reversible.
- General Function
- Oxygen binding
- 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
- CYP3A7
- Uniprot ID
- P24462
- Uniprot Name
- Cytochrome P450 3A7
- Molecular Weight
- 57525.03 Da
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- Curator comments
- Inhibition is reversible.
- General Function
- Monooxygenase activity
- Specific Function
- Exhibits low testosterone 6-beta-hydroxylase activity.
- Gene Name
- CYP3A43
- Uniprot ID
- Q9HB55
- Uniprot Name
- Cytochrome P450 3A43
- Molecular Weight
- 57669.21 Da
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Steroid hydroxylase activity
- Specific Function
- Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and im...
- Gene Name
- CYP2C19
- Uniprot ID
- P33261
- Uniprot Name
- Cytochrome P450 2C19
- Molecular Weight
- 55930.545 Da
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- Curator comments
- Inhibition is reversible.
- General Function
- Steroid 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 oxidizes a variety of structurally un...
- Gene Name
- CYP2C9
- Uniprot ID
- P11712
- Uniprot Name
- Cytochrome P450 2C9
- Molecular Weight
- 55627.365 Da
References
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Steroid 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 oxidizes a variety of structurally un...
- Gene Name
- CYP2C8
- Uniprot ID
- P10632
- Uniprot Name
- Cytochrome P450 2C8
- Molecular Weight
- 55824.275 Da
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Steroid binding
- Specific Function
- UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform glucuronidates bilirubin IX-alpha to form both the...
- Gene Name
- UGT1A1
- Uniprot ID
- P22309
- Uniprot Name
- UDP-glucuronosyltransferase 1-1
- Molecular Weight
- 59590.91 Da
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- SubstrateInhibitor
- Curator comments
- Rucaparib is an inhibitos of P-gp efflux transporters with an IC50 value of 283 uM [FDA Label].
- General Function
- Xenobiotic-transporting atpase activity
- Specific Function
- Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
- Gene Name
- ABCB1
- Uniprot ID
- P08183
- Uniprot Name
- Multidrug resistance protein 1
- Molecular Weight
- 141477.255 Da
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- SubstrateInhibitor
- Curator comments
- Rucaparib is an inhibitor of BCRP with an IC50 value of 55uM [FDA Label].
- General Function
- Xenobiotic-transporting atpase activity
- Specific Function
- High-capacity urate exporter functioning in both renal and extrarenal urate excretion. Plays a role in porphyrin homeostasis as it is able to mediates the export of protoporhyrin IX (PPIX) both fro...
- Gene Name
- ABCG2
- Uniprot ID
- Q9UNQ0
- Uniprot Name
- ATP-binding cassette sub-family G member 2
- Molecular Weight
- 72313.47 Da
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Monovalent cation:proton antiporter activity
- Specific Function
- Solute transporter for tetraethylammonium (TEA), 1-methyl-4-phenylpyridinium (MPP), cimetidine, N-methylnicotinamide (NMN), metformin, creatinine, guanidine, procainamide, topotecan, estrone sulfat...
- Gene Name
- SLC47A1
- Uniprot ID
- Q96FL8
- Uniprot Name
- Multidrug and toxin extrusion protein 1
- Molecular Weight
- 61921.585 Da
References
- Kristeleit R, Shapiro GI, Burris HA, Oza AM, LoRusso P, Patel MR, Domchek SM, Balmana J, Drew Y, Chen LM, Safra T, Montes A, Giordano H, Maloney L, Goble S, Isaacson J, Xiao J, Borrow J, Rolfe L, Shapira-Frommer R: A Phase I-II Study of the Oral PARP Inhibitor Rucaparib in Patients with Germline BRCA1/2-Mutated Ovarian Carcinoma or Other Solid Tumors. Clin Cancer Res. 2017 Aug 1;23(15):4095-4106. doi: 10.1158/1078-0432.CCR-16-2796. Epub 2017 Mar 6. [Article]
- Rucaparib FDA label [File]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- Curator comments
- Rucaparib has been shown to only inhibit the MATE-2K transporter.
- General Function
- Drug transmembrane transporter activity
- Specific Function
- Solute transporter for tetraethylammonium (TEA), 1-methyl-4-phenylpyridinium (MPP), cimetidine, N-methylnicotinamide, metformin, creatinine, guanidine, procainamide, topotecan, estrone sulfate, acy...
- Gene Name
- SLC47A2
- Uniprot ID
- Q86VL8
- Uniprot Name
- Multidrug and toxin extrusion protein 2
- Molecular Weight
- 65083.915 Da
References
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- Curator comments
- The inhibition is moderate.
- General Function
- Secondary active organic cation transmembrane transporter activity
- Specific Function
- Translocates a broad array of organic cations with various structures and molecular weights including the model compounds 1-methyl-4-phenylpyridinium (MPP), tetraethylammonium (TEA), N-1-methylnico...
- Gene Name
- SLC22A1
- Uniprot ID
- O15245
- Uniprot Name
- Solute carrier family 22 member 1
- Molecular Weight
- 61153.345 Da
References
- 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. [Article]
- Dockery LE, Gunderson CC, Moore KN: Rucaparib: the past, present, and future of a newly approved PARP inhibitor for ovarian cancer. Onco Targets Ther. 2017 Jun 19;10:3029-3037. doi: 10.2147/OTT.S114714. eCollection 2017. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- Curator comments
- Weak inhibition was observed at ultra-therapeutic concentration (300 µM) of rucaparib [FDA Label].
- General Function
- Atpase activity, coupled to transmembrane movement of substances
- Specific Function
- May be an organic anion pump relevant to cellular detoxification.
- Gene Name
- ABCC4
- Uniprot ID
- O15439
- Uniprot Name
- Multidrug resistance-associated protein 4
- Molecular Weight
- 149525.33 Da
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- Curator comments
- Weak inhibition was observed at ultra-therapeutic concentration (300 µM) of rucaparib [FDA Label].
- General Function
- Sodium-independent organic anion transmembrane transporter activity
- Specific Function
- Mediates the Na(+)-independent uptake of organic anions such as pravastatin, taurocholate, methotrexate, dehydroepiandrosterone sulfate, 17-beta-glucuronosyl estradiol, estrone sulfate, prostagland...
- Gene Name
- SLCO1B1
- Uniprot ID
- Q9Y6L6
- Uniprot Name
- Solute carrier organic anion transporter family member 1B1
- Molecular Weight
- 76447.99 Da
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- Curator comments
- Weak inhibition was observed at ultra-therapeutic concentration (300 µM) of rucaparib [FDA Label].
- General Function
- Sodium-independent organic anion transmembrane transporter activity
- Specific Function
- Mediates the Na(+)-independent uptake of organic anions such as 17-beta-glucuronosyl estradiol, taurocholate, triiodothyronine (T3), leukotriene C4, dehydroepiandrosterone sulfate (DHEAS), methotre...
- Gene Name
- SLCO1B3
- Uniprot ID
- Q9NPD5
- Uniprot Name
- Solute carrier organic anion transporter family member 1B3
- Molecular Weight
- 77402.175 Da
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- Curator comments
- Weak inhibition was observed at ultra-therapeutic concentration (300 µM) of rucaparib [FDA Label].
- General Function
- Sodium-independent organic anion transmembrane transporter activity
- Specific Function
- Involved in the renal elimination of endogenous and exogenous organic anions. Functions as organic anion exchanger when the uptake of one molecule of organic anion is coupled with an efflux of one ...
- Gene Name
- SLC22A6
- Uniprot ID
- Q4U2R8
- Uniprot Name
- Solute carrier family 22 member 6
- Molecular Weight
- 61815.78 Da
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- Curator comments
- Weak inhibition was observed at ultra-therapeutic concentration (300 µM) of rucaparib [FDA Label].
- General Function
- Sodium-independent organic anion transmembrane transporter activity
- Specific Function
- Plays an important role in the excretion/detoxification of endogenous and exogenous organic anions, especially from the brain and kidney. Involved in the transport basolateral of steviol, fexofenad...
- Gene Name
- SLC22A8
- Uniprot ID
- Q8TCC7
- Uniprot Name
- Solute carrier family 22 member 8
- Molecular Weight
- 59855.585 Da
Drug created on October 20, 2016 21:59 / Updated on April 20, 2021 00:38