Rucaparib

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Chemical compound

title: "Rucaparib" type: doc version: 1 created: 2026-02-28 author: "Wikipedia contributors" status: active scope: public tags: ["benzazepines", "cancer-treatments", "cyp2d6-inhibitors", "n-acyltryptamines", "lactams", "parp-inhibitors", "fluoroarenes", "orphan-drugs"] description: "Chemical compound" topic_path: "general/benzazepines" source: "https://en.wikipedia.org/wiki/Rucaparib" license: "CC BY-SA 4.0" wikipedia_page_id: 0 wikipedia_revision_id: 0

::summary Chemical compound ::

::data[format=table title="Infobox drug"]

Field	Value
image	Rucaparib.svg
image_class	skin-invert-image
caption	Above: molecular structure of rucaparib
image2	Rucaparib 3D.png
image_class2	bg-transparent
pronounce
tradename	Rubraca
Drugs.com
MedlinePlus	a617002
DailyMedID	Rucaparib
pregnancy_AU
pregnancy_category	Not recommended
routes_of_administration	By mouth
ATC_prefix	L01
ATC_suffix	XK03
legal_AU
legal_BR
legal_CA
legal_DE
legal_NZ
legal_UK	POM
legal_UK_comment
legal_US	Rx-only
legal_US_comment
legal_EU	Rx-only
legal_EU_comment
legal_UN
legal_status	Rx-only
bioavailability	30–45% (Tmax = 1.9 hours)
protein_bound	70% (in vitro)
metabolism	Liver (primarily CYP2D6; 1A2 and 3A4 to a lesser extent)
elimination_half-life	17–19 hours
index2_label	as salt
CAS_number	283173-50-2
CAS_number2	1859053-21-6
PubChem	9931954
PubChem2	121490161
IUPHAR_ligand	7736
DrugBank	DB12332
DrugBank2	DBSALT001982
ChemSpiderID	8107584
ChemSpiderID2	57643660
UNII	8237F3U7EH
UNII2	41AX9SJ8KO
KEGG	D10079
KEGG2	D10982
ChEBI	134689
ChEBI2	134692
ChEMBL	1173055
ChEMBL2	3833368
PDB_ligand	RPB
synonyms	CO-338, AG-014699, PF-0136738, PF-01367338
IUPAC_name	8-Fluoro-2-{4-[(methylamino)methyl]phenyl}-1,3,4,5-tetrahydro-6H-azepino[5,4,3-cd]indol-6-one
C	19
H	18
F	1
N	3
O	1
SMILES	CNCc1ccc(cc1)c2[nH]c3cc(F)cc4C(=O)NCCc2c34
StdInChI	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)
StdInChIKey	HMABYWSNWIZPAG-UHFFFAOYSA-N
::

| IUPAC_name = 8-Fluoro-2-{4-[(methylamino)methyl]phenyl}-1,3,4,5-tetrahydro-6H-azepino[5,4,3-cd]indol-6-one | C = 19 | H = 18 | F = 1 | N = 3 | O = 1 | SMILES = CNCc1ccc(cc1)c2[nH]c3cc(F)cc4C(=O)NCCc2c34 | StdInChI = 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) | StdInChI_comment = | StdInChIKey = HMABYWSNWIZPAG-UHFFFAOYSA-N | density = | density_notes = | melting_point = | melting_high = | melting_notes = | boiling_point = | boiling_notes = | solubility = | sol_units = | specific_rotation =

Rucaparib, sold under the brand name Rubraca, is a PARP inhibitor used as an anti-cancer agent. Rucaparib is a first-in-class pharmaceutical drug targeting the DNA repair enzyme poly-ADP ribose polymerase-1 (PARP-1). It is taken by mouth.

The most common side effects include tiredness or weakness, nausea (feeling sick), increased levels of creatinine (which may indicate kidney problems) and liver enzymes in the blood (which may indicate liver damage), vomiting, anaemia (low red blood cell counts), decreased appetite, dysgeusia (taste disturbances), diarrhoea, thrombocytopenia (low levels of platelets) and abdominal pain (belly ache).

Medical uses

Rucaparib is indicated as monotherapy for the maintenance treatment of adults with platinum-sensitive relapsed high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in response (complete or partial) to platinum-based chemotherapy.

In the United States, rucaparib is also indicated for the treatment of prostate cancer. In December 2025, rucaparib received regular approval in the US for the treatment of adults with a deleterious BRCA mutation (BRCAm) (germline and/or somatic)-associated metastatic castration-resistant prostate cancer (mCRPC) previously treated with an androgen receptor-directed therapy.

Pharmacology

Mechanism of action

Rucaparib inhibits "the contraction of isolated vascular smooth muscle, including that from the tumours of cancer patients. It also reduces the migration of some cancer and normal cells in culture."

As a PARP inhibitor, rucaparib is expected to be more effective in the 9% of pancreatic cancers with a BRCA mutation (BRCA1 or BRCA2).

History

It was discovered as part of a collaboration between scientists working at the Northern Institute of Cancer Research and Medical School of Newcastle University and Agouron Pharmaceuticals in San Diego, California. It was being developed by Clovis Oncology until it was sold to Pharmaand GmbH (Pharma&) as part of Clovis's bankruptcy proceedings.

Society and culture

Legal status

In December 2016, the US Food and Drug Administration (FDA) granted an accelerated approval for use in cases of pretreated advanced ovarian cancer.

It was designated an orphan medicinal product in the European Union in October 2012. In March 2018, the Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion, recommending the granting of a conditional marketing authorization, intended for the treatment of relapsed or progressive ovarian cancer. It was approved for medical use in the European Union in May 2018.

Research

Clinical trials

After the FDA approval, TRITON2 and TRITON3 mCRPC studies were initiated in order to determine how patients with prostate cancer will respond to the rucaparib drug. The studies for these two trials are still going on and the estimated dates for the first results are range between 2019 and 2022.

The ARIEL3 and ARIEL4 are two randomized, double-blind phase III studies. The ARIEL3 study was designed to evaluate the effect of the investigational agent as a maintenance treatment for the advanced platinum-sensitive ovarian cancer patients compared placebo after their response to at least two prior chemotherapies. The top-line results from the study were presented at the ESMO 2017 congress and right after that, it was published in the Lancet journal in September 2017. The findings showed significant improvement in progression-free survival (PFS) in patients treated with Rubraca than placebo. Recently, in October 2017, a supplemental sNDA for the rucaparib ARIEL3 maintenance treatment has been submitted to the FDA.

Interim results from the ARIEL4 study to evaluate how patients will best respond to treatment with rucaparib compared with chemotherapy show a decrease in overall survival compared to standard of care. A detrimental effect in terms of overall survival (OS) has been observed for rucaparib compared to the chemotherapy-containing control arm (19.6 months and 27.1 months respectively with a Hazard Ratio (HR) of 1.550 (95% CI: 1.085, 2.214), p=0.0161) following a planned interim analysis (IA) in the post-approval randomized controlled study CO-338-043 (ARIEL4).

References

(19 June 2019). "Rubraca 200mg film-coated tablets - Summary of Product Characteristics (SmPC)".
(6 April 2018). "Rubraca- rucaparib tablet, film coated".
(10 January 2012). "Cancer Research Launches New Drug Trial". Hearst Magazines UK.
(6 April 2018). "FDA approves rucaparib".
(17 December 2025). "FDA grants regular approval to rucaparib for metastatic castration-resistant prostate cancer".
"Does the PARP inhibitor AG014699 act via the nucleotide P2 receptor?". School of Pharmacy - PhD Projects 2009.
"Rucaparib shows clinical benefit in pancreatic cancer patients with BRCA mutation".
(November 2000). "Resistance-modifying agents. 9. Synthesis and biological properties of benzimidazole inhibitors of the DNA repair enzyme poly(ADP-ribose) polymerase". Journal of Medicinal Chemistry.
Bell, Jacob. (2023-04-07). "Navigating bankruptcy, Clovis reaches deal to sell cancer drug Rubraca".
(19 December 2016). "PARP Inhibitor Gets FDA Nod for Ovarian Cancer". MedPage Today, LLC..
(30 January 2017). "Rubraca (rucaparib) Tablets".
(17 September 2018). "EU/3/12/1049: Orphan designation for the treatment of ovarian cancer".
(22 March 2018). "Rubraca". European Medical Agency.
(17 September 2018). "Rubraca EPAR".
"Rucaparib Clinical Overview". Clovis Oncology.
(October 2017). "Rucaparib maintenance treatment for recurrent ovarian carcinoma after response to platinum therapy (ARIEL3): a randomised, double-blind, placebo-controlled, phase 3 trial". Lancet.
(6 May 2022). "Rucaparib (Rubraca): interim data from Study CO-338-043 (ARIEL4) show a decrease in overall survival compared to standard of care".
(November 2017). "ARIEL3: a phase 3, randomised, double-blind study of rucaparib vs placebo following response to platinum-based chemotherapy for recurrent ovarian carcinoma (OC)".

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