Identification

Summary

Rucaparib is a poly (ADP-ribose) polymerase (PARP) inhibitor used to treat recurrent ovarian and prostate cancers in previously treated adults.

Brand Names
Rubraca
Generic Name
Rucaparib
DrugBank Accession Number
DB12332
Background

Rucaparib is an anticancer drug and poly (ADP-ribose) polymerase (PARP) inhibitor. PARP is an enzyme that plays an essential role in DNA repair.1 Rucaparib is proposed to work in several PARP-dependent and PARP-independent mechanisms of action; however, it causes a unique effect of synthetic lethality. By targeting the genetically-mutated cancer cells that lack a DNA repair mechanism, rucaparib causes cancer cell death and reduces tumour growth.1,2

Rucaparib was granted FDA Breakthrough Therapy designation in April 2015 1 and accelerated approval in December 2016.4 The drug was later approved by the European Commission in May 2018.7 It is currently used to treat recurrent ovarian and prostate cancer in adults.6,7

Type
Small Molecule
Groups
Approved, Investigational
Structure
Weight
Average: 323.371
Monoisotopic: 323.143390375
Chemical Formula
C19H18FN3O
Synonyms
  • Rucaparib
External IDs
  • AG-14447

Pharmacology

Indication

Rucaparib is indicated for the maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to platinum-based chemotherapy.6

Under accelerated approval by the FDA, rucaparib is also indicated for the treatment of adult patients with a deleterious BRCA mutation (germline and/or somatic)-associated metastatic castration-resistant prostate cancer (mCRPC) who have been treated with androgen receptor-directed therapy and a taxane-based chemotherapy.6

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Associated Conditions
Associated Therapies
Contraindications & Blackbox Warnings
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Pharmacodynamics

Rucaparib is an anticancer agent that exerts cytotoxic effects against cancer cells. It works by inhibiting poly (ADP-ribose) polymerase (PARP), an enzyme that plays a role in DNA repair. Rucaparib inhibits PARP-1, PARP-2, and PARP-3. It also interacts with PARP-4, PARP-10, PARP-12, PARP-15, and PARP-16, but to a lesser extent.1 In mice, rucaparib accumulated and was retained in tumours, inhibiting PARP enzymes for seven days.4

Rucaparib decreases tumour growth in tumour cell lines with deficiencies in BRCA1/2 and other DNA repair genes.6 In addition to PARP inhibition, rucaparib demonstrated PARP-independent cytotoxic mechanisms in cancer cells. When co-administered with other chemotherapeutic agents, rucaparib contributed to synergistic or additive effects in vitro and in vivo. There is evidence that rucaparib can sensitize cancer cells to chemotherapy. Rucaparib can also cause vasodilation, which may increase tumour perfusion and enhance the accumulation of cytotoxic drugs in cancer cells.4

Mechanism of action

PARPs play a role in DNA repair by activating DNA damage response pathways, such as base excision repair, and facilitating DNA repair. PARPs were evaluated as novel anticancer therapeutic targets after discovering that PARP-1 inhibitors reduce tumour growth in BRCA-deficient cancers.1 BRCA1 and BRCA2 are tumour suppressor genes involved in various cellular processes related to cell growth and death, including DNA repair.3 More specifically, BRCA1 and BRCA2 are involved in homologous recombination (HR) DNA repair. Cancer cells with a deleterious BRCA mutation are HR-deficient, resulting in unregulated and aberrant cell repair and growth.1

Rucaparib inhibits PARP1, PARP2, and PARP3.6 Inhibiting PARP traps the enzyme on damaged DNA, halting the repair process and forming toxic PARP–DNA complexes. Alternatively, other DNA repair processes such as error-prone nonhomologous end joining (NHEJ) or alternative end-joining pathways can be initiated, leading to mutations or chromosomal change.2 Further DNA damage can trigger cancer cell apoptosis and cell death.6

Typically, inhibition of PARP converts single-strand breaks in DNA to double-strand breaks at replication forks. HR DNA repair pathways repair double-strand breaks; however, HR-deficient cancer cells lack this repair mechanism. Because HR-deficient cancer cells are more vulnerable to unsalvageable DNA damage, rucaparib-induced PARP inhibition leads to synthetic lethality. In this phenomenon, two non-lethal defects (HR deficiency and PARP inhibition) combine and cause cell death.1,2

TargetActionsOrganism
APoly [ADP-ribose] polymerase 1
inhibitor
Humans
APoly [ADP-ribose] polymerase 2
inhibitor
Humans
APoly [ADP-ribose] polymerase 3
inhibitor
Humans
Absorption

Rucaparib exhibits a linear pharmacokinetic profile over the dose range from 240 mg to 840 mg twice daily. The mean (coefficient of variation [CV]) steady-state rucaparib Cmax is 1940 ng/mL (54%) and AUC0-12h is 16900 h x ng/mL (54%) at the approved recommended dosage. The mean AUC accumulation ratio is 3.5 to 6.2 fold. The median Tmax at the steady state is 1.9 hours, with a range of 0 to 5.98 hours at the approved recommended dosage. The mean absolute bioavailability is 36%, with a range of 30 to 45%.6

A high-fat meal increased Cmax and AUC0-24h by 20% and 38%, respectively. The Tmax was delayed by 2.5 hours.6

Volume of distribution

The mean (coefficient of variation) apparent volume of distribution is 2300 L (21%).6

Protein binding

Rucaparib is 70% bound to human plasma proteins in vitro. Rucaparib preferentially distributed to red blood cells with a blood-to-plasma concentration ratio of 1.8.6

Metabolism

In vitro, rucaparib is primarily metabolized by CYP2D6 and, to a lesser extent, by CYP1A2 and CYP3A4. In addition to CYP-based oxidation, rucaparib also undergoes N-demethylation, N-methylation, and glucuronidation.6 In one study, seven metabolites of rucaparib were identified in plasma, urine, and feces.5

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Route of elimination

Following a single oral dose of radiolabeled rucaparib, unchanged rucaparib accounted for 64% of the radioactivity. Rucaparib accounted for 45% and 95% of radioactivity in urine and feces, respectively.6

Half-life

The mean (coefficient of variation) terminal elimination half-life is 26 (39%) hours.6

Clearance

The mean (coefficient of variation) apparent total clearance at steady state is 44.2 L/h (45%).6

Adverse Effects
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Toxicity

There is no information regarding the LD50 and overdose of rucaparib.

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.
DrugInteraction
AbametapirThe serum concentration of Rucaparib can be increased when it is combined with Abametapir.
AbataceptThe metabolism of Rucaparib can be increased when combined with Abatacept.
AbemaciclibThe metabolism of Abemaciclib can be decreased when combined with Rucaparib.
AbirateroneThe serum concentration of Rucaparib can be increased when it is combined with Abiraterone.
AbrocitinibThe metabolism of Abrocitinib can be decreased when combined with Rucaparib.
AcalabrutinibThe metabolism of Acalabrutinib can be decreased when combined with Rucaparib.
AcebutololThe metabolism of Acebutolol can be decreased when combined with Rucaparib.
AcenocoumarolThe metabolism of Acenocoumarol can be decreased when combined with Rucaparib.
AcetaminophenThe metabolism of Acetaminophen can be decreased when combined with Rucaparib.
AcetohexamideThe metabolism of Acetohexamide can be decreased when combined with Rucaparib.
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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. A high-fat meals increases drug exposure but not to a clinically significant extent.

Products

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Product Ingredients
IngredientUNIICASInChI Key
Rucaparib camsylate41AX9SJ8KO1859053-21-6INBJJAFXHQQSRW-STOWLHSFSA-N
Rucaparib phosphateH3M9955244459868-92-9FCCGJTKEKXUBFZ-UHFFFAOYSA-N
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
RubracaTablet, film coated300 mg/1OralClovis Oncology, Inc.2016-12-19Not applicableUS flag
RubracaTablet, film coated300 mgOralClovis Oncology Ireland Limited2020-12-16Not applicableEU flag
RubracaTablet, film coated200 mgOralClovis Oncology Ireland Limited2020-12-16Not applicableEU flag
RubracaTablet, film coated200 mg/1OralClovis Oncology, Inc.2016-12-19Not applicableUS flag
RubracaTablet, film coated250 mgOralClovis Oncology Ireland Limited2020-12-16Not applicableEU flag
RubracaTablet, film coated250 mg/1OralClovis Oncology, Inc.2017-05-01Not applicableUS flag

Categories

ATC Codes
L01XX55 — Rucaparib
Drug Categories
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
  1. 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]
  2. 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]
  3. Varol U, Kucukzeybek Y, Alacacioglu A, Somali I, Altun Z, Aktas S, Oktay Tarhan M: BRCA genes: BRCA 1 and BRCA 2. J BUON. 2018 Jul-Aug;23(4):862-866. [Article]
  4. Syed YY: Rucaparib: First Global Approval. Drugs. 2017 Apr;77(5):585-592. doi: 10.1007/s40265-017-0716-2. [Article]
  5. Liao M, Watkins S, Nash E, Isaacson J, Etter J, Beltman J, Fan R, Shen L, Mutlib A, Kemeny V, Papai Z, van Tilburg P, Xiao JJ: Evaluation of absorption, distribution, metabolism, and excretion of [(14)C]-rucaparib, a poly(ADP-ribose) polymerase inhibitor, in patients with advanced solid tumors. Invest New Drugs. 2020 Jun;38(3):765-775. doi: 10.1007/s10637-019-00815-2. Epub 2019 Jun 27. [Article]
  6. FDA Approved Drug Products: RUBRACA (rucaparib) tablets, for oral use (June 2022) [Link]
  7. EMA Approved Drug Products: Rubraca (rucaparib) Oral Tablets [Link]
KEGG Drug
D10079
PubChem Compound
9931954
PubChem Substance
347828593
ChemSpider
8107584
BindingDB
50446130
RxNav
1862579
ChEBI
134689
ChEMBL
CHEMBL1173055
ZINC
ZINC000000025958
PharmGKB
PA166163418
PDBe Ligand
RPB
Wikipedia
Rucaparib
PDB Entries
4bjc / 4rv6 / 6vkk

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
3Active Not RecruitingTreatmentComplete Response / Epithelial Ovarian Cancer / Fallopian Tubes Cancer / FIGO Stage III-IV / Newly Diagnosed / Partial Response / Primary Peritoneal1
3Active Not RecruitingTreatmentEpithelial Ovarian Cancer / Fallopian Tubes Cancer / Malignant Peritoneal Neoplasm / Ovarian Cancer1
3Active Not RecruitingTreatmentFallopian Tubes Cancer / Malignant Peritoneal Neoplasm / Ovarian Cancer1
3Active Not RecruitingTreatmentMetastatic Castration Resistant Prostate Cancer (CRPC)1
3Enrolling by InvitationTreatmentEpithelial Ovarian Cancer / Fallopian Tubes Cancer / Malignant Peritoneal Neoplasm / Metastatic Castration Resistant Prostate Cancer (CRPC) / Other Solid Tumors / Ovarian Cancer1
3RecruitingTreatmentCastration-Resistant Prostate Carcinoma / Metastatic Prostate Adenocarcinoma / Stage IV Prostate Cancer AJCC v8 / Stage IVA Prostate Cancer AJCC v8 / Stage IVB Prostate Cancer AJCC v81
3RecruitingTreatmentClear Cell Carcinoma / Fallopian Tubes Cancer / Ovarian Cancer / Primary Peritoneal Cancer1
2Active Not RecruitingTreatmentAdvanced Gastric Cancer1
2Active Not RecruitingTreatmentCarcinoma, Squamous Cell, Non-small-cell Lung / Deleterious BRCA1 Gene Mutation / Deleterious BRCA2 Gene Mutation / Loss of Heterozygosity / Recurrent Lung Adenocarcinoma / Recurrent Lung Large Cell Carcinoma / Recurrent Non-Small Cell Lung Carcinoma / Recurrent Non-Squamous Non-Small Cell Lung Carcinoma / Stage IV Lung Cancer AJCC v8 / Stage IVA Lung Cancer AJCC v8 / Stage IVB Lung Cancer AJCC v81
2Active Not RecruitingTreatmentCervical Cancer / Endometrial Cancer1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
Tablet, film coatedOral200 mg/1
Tablet, film coatedOral200 MG
Tablet, film coatedOral250 mg/1
Tablet, film coatedOral250 MG
Tablet, film coatedOral300 mg/1
Tablet, film coatedOral300 MG
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US8859562No2014-10-142031-08-04US flag
US8143241No2012-03-272027-08-12US flag
US6495541No2002-12-172020-01-10US flag
US8754072No2014-06-172031-02-10US flag
US9045487No2015-06-022031-02-10US flag
US8071579No2011-12-062027-08-12US flag
US7531530No2009-05-122024-07-23US flag
US7351701No2008-04-012024-07-23US flag
US9861638No2018-01-092031-02-10US flag
US9987285No2018-06-052035-08-17US flag
US10130636No2018-11-202035-08-17US flag
US10278974No2019-05-072031-02-10US flag

Properties

State
Solid
Experimental Properties
PropertyValueSource
water solubility1 mg/mLhttps://www.accessdata.fda.gov/drugsatfda_docs/label/2022/209115s011lbl.pdf
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

Targets

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Use our structured and evidence-based datasets to unlock new
insights and accelerate drug research.
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Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
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
References
  1. 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]
  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. [Article]
  3. FDA Approved Drug Products: RUBRACA (rucaparib) tablets, for oral use (June 2022) [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
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
References
  1. 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]
  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. [Article]
  3. FDA Approved Drug Products: RUBRACA (rucaparib) tablets, for oral use (June 2022) [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
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
References
  1. 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]
  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. [Article]
  3. FDA Approved Drug Products: RUBRACA (rucaparib) tablets, for oral use (June 2022) [Link]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
Inhibitor
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
References
  1. FDA Approved Drug Products: RUBRACA (rucaparib) tablets, for oral use (June 2022) [Link]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
Inhibitor
Inducer
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
  1. 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]
  2. Liao M, Jaw-Tsai S, Beltman J, Simmons AD, Harding TC, Xiao JJ: Evaluation of in vitro absorption, distribution, metabolism, and excretion and assessment of drug-drug interaction of rucaparib, an orally potent poly(ADP-ribose) polymerase inhibitor. Xenobiotica. 2020 Sep;50(9):1032-1042. doi: 10.1080/00498254.2020.1737759. Epub 2020 Mar 18. [Article]
  3. Xiao JJ, Nowak D, Ramlau R, Tomaszewska-Kiecana M, Wysocki PJ, Isaacson J, Beltman J, Nash E, Kaczanowski R, Arold G, Watkins S: Evaluation of Drug-Drug Interactions of Rucaparib and CYP1A2, CYP2C9, CYP2C19, CYP3A, and P-gp Substrates in Patients With an Advanced Solid Tumor. Clin Transl Sci. 2019 Jan;12(1):58-65. doi: 10.1111/cts.12600. Epub 2018 Dec 20. [Article]
  4. Rucaparib - Drug Summary Prescribers Digital Reference [Link]
  5. FDA Approved Drug Products: RUBRACA (rucaparib) tablets, for oral use (June 2022) [Link]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
Inhibitor
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
  1. Xiao JJ, Nowak D, Ramlau R, Tomaszewska-Kiecana M, Wysocki PJ, Isaacson J, Beltman J, Nash E, Kaczanowski R, Arold G, Watkins S: Evaluation of Drug-Drug Interactions of Rucaparib and CYP1A2, CYP2C9, CYP2C19, CYP3A, and P-gp Substrates in Patients With an Advanced Solid Tumor. Clin Transl Sci. 2019 Jan;12(1):58-65. doi: 10.1111/cts.12600. Epub 2018 Dec 20. [Article]
  2. FDA Approved Drug Products: RUBRACA (rucaparib) tablets, for oral use (June 2022) [Link]
Kind
Protein
Organism
Humans
Pharmacological action
No
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
References
  1. Liao M, Jaw-Tsai S, Beltman J, Simmons AD, Harding TC, Xiao JJ: Evaluation of in vitro absorption, distribution, metabolism, and excretion and assessment of drug-drug interaction of rucaparib, an orally potent poly(ADP-ribose) polymerase inhibitor. Xenobiotica. 2020 Sep;50(9):1032-1042. doi: 10.1080/00498254.2020.1737759. Epub 2020 Mar 18. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
No
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
References
  1. Liao M, Jaw-Tsai S, Beltman J, Simmons AD, Harding TC, Xiao JJ: Evaluation of in vitro absorption, distribution, metabolism, and excretion and assessment of drug-drug interaction of rucaparib, an orally potent poly(ADP-ribose) polymerase inhibitor. Xenobiotica. 2020 Sep;50(9):1032-1042. doi: 10.1080/00498254.2020.1737759. Epub 2020 Mar 18. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
No
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
References
  1. Liao M, Jaw-Tsai S, Beltman J, Simmons AD, Harding TC, Xiao JJ: Evaluation of in vitro absorption, distribution, metabolism, and excretion and assessment of drug-drug interaction of rucaparib, an orally potent poly(ADP-ribose) polymerase inhibitor. Xenobiotica. 2020 Sep;50(9):1032-1042. doi: 10.1080/00498254.2020.1737759. Epub 2020 Mar 18. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
No
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
References
  1. Liao M, Jaw-Tsai S, Beltman J, Simmons AD, Harding TC, Xiao JJ: Evaluation of in vitro absorption, distribution, metabolism, and excretion and assessment of drug-drug interaction of rucaparib, an orally potent poly(ADP-ribose) polymerase inhibitor. Xenobiotica. 2020 Sep;50(9):1032-1042. doi: 10.1080/00498254.2020.1737759. Epub 2020 Mar 18. [Article]
  2. Xiao JJ, Nowak D, Ramlau R, Tomaszewska-Kiecana M, Wysocki PJ, Isaacson J, Beltman J, Nash E, Kaczanowski R, Arold G, Watkins S: Evaluation of Drug-Drug Interactions of Rucaparib and CYP1A2, CYP2C9, CYP2C19, CYP3A, and P-gp Substrates in Patients With an Advanced Solid Tumor. Clin Transl Sci. 2019 Jan;12(1):58-65. doi: 10.1111/cts.12600. Epub 2018 Dec 20. [Article]
  3. FDA Approved Drug Products: RUBRACA (rucaparib) tablets, for oral use (June 2022) [Link]
Kind
Protein
Organism
Humans
Pharmacological action
No
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
  1. Liao M, Jaw-Tsai S, Beltman J, Simmons AD, Harding TC, Xiao JJ: Evaluation of in vitro absorption, distribution, metabolism, and excretion and assessment of drug-drug interaction of rucaparib, an orally potent poly(ADP-ribose) polymerase inhibitor. Xenobiotica. 2020 Sep;50(9):1032-1042. doi: 10.1080/00498254.2020.1737759. Epub 2020 Mar 18. [Article]
  2. Xiao JJ, Nowak D, Ramlau R, Tomaszewska-Kiecana M, Wysocki PJ, Isaacson J, Beltman J, Nash E, Kaczanowski R, Arold G, Watkins S: Evaluation of Drug-Drug Interactions of Rucaparib and CYP1A2, CYP2C9, CYP2C19, CYP3A, and P-gp Substrates in Patients With an Advanced Solid Tumor. Clin Transl Sci. 2019 Jan;12(1):58-65. doi: 10.1111/cts.12600. Epub 2018 Dec 20. [Article]
  3. DailyMed Label: RUBRACA (rucaparib) oral tablet, film coated [Link]
  4. EMA Reports [Link]
  5. Rubraca [Link]
Kind
Protein
Organism
Humans
Pharmacological action
No
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
References
  1. FDA Approved Drug Products: RUBRACA (rucaparib) tablets, for oral use (June 2022) [Link]
Kind
Protein
Organism
Humans
Pharmacological action
No
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
References
  1. FDA Approved Drug Products: RUBRACA (rucaparib) tablets, for oral use (June 2022) [Link]

Transporters

Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
Inhibitor
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
References
  1. FDA Approved Drug Products: RUBRACA (rucaparib) tablets, for oral use (June 2022) [Link]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
Inhibitor
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
References
  1. FDA Approved Drug Products: RUBRACA (rucaparib) tablets, for oral use (June 2022) [Link]
Kind
Protein
Organism
Humans
Pharmacological action
No
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
  1. 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]
  2. FDA Approved Drug Products: RUBRACA (rucaparib) tablets, for oral use (June 2022) [Link]
Kind
Protein
Organism
Humans
Pharmacological action
No
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
  1. Colombo I, Lheureux S, Oza AM: Rucaparib: a novel PARP inhibitor for BRCA advanced ovarian cancer. Drug Des Devel Ther. 2018 Mar 21;12:605-617. doi: 10.2147/DDDT.S130809. eCollection 2018. [Article]
  2. FDA Approved Drug Products: RUBRACA (rucaparib) tablets, for oral use (June 2022) [Link]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Inhibitor
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
  1. 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]
  2. 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]
  3. FDA Approved Drug Products: RUBRACA (rucaparib) tablets, for oral use (June 2022) [Link]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Inhibitor
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
References
  1. FDA Approved Drug Products: RUBRACA (rucaparib) tablets, for oral use (June 2022) [Link]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Inhibitor
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
References
  1. FDA Approved Drug Products: RUBRACA (rucaparib) tablets, for oral use (June 2022) [Link]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Inhibitor
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
References
  1. FDA Approved Drug Products: RUBRACA (rucaparib) tablets, for oral use (June 2022) [Link]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Inhibitor
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
References
  1. FDA Approved Drug Products: RUBRACA (rucaparib) tablets, for oral use (June 2022) [Link]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Inhibitor
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
References
  1. FDA Approved Drug Products: RUBRACA (rucaparib) tablets, for oral use (June 2022) [Link]

Drug created at October 20, 2016 21:59 / Updated at June 23, 2022 05:52