Ligand id: 7736

Name: rucaparib

Structure and Physico-chemical Properties

2D Structure
Calculated Physico-chemical Properties
Hydrogen bond acceptors 4
Hydrogen bond donors 3
Rotatable bonds 3
Topological polar surface area 56.92
Molecular weight 323.14
XLogP 2.71
No. Lipinski's rules broken 0

Molecular properties generated using the CDK

No information available.
Summary of Clinical Use
In December 2016, the US FDA granted accelerated approval to rucaparib for treatment of patients with deleterious germline and/or somatic BRCA mutation associated advanced ovarian cancer who have been treated with two or more chemotherapies. Link here to a list of clinical trials assessing rucaparib registered with Phase 2 trial results are published in [5]. In April 2017, the FDA expanded approval to include use of rucaparib as maintenance treatment for recurrent ovarian, fallopian tube, or primary peritoneal cancer for patients who are in a complete or partial response to platinum-based chemotherapy. This desision was based on results from clinical trial NCT01968213 which were published in October 2017 [2]. Approval was further expanded by the FDA in April 2018, to include use as a maintenance treatment for epithelial ovarian cancer, fallopian tube, or primary peritoneal cancer that is in complete or partial response to platinum-based chemotherapy (based on results from the ARIEL3 study NCT01968213).
The EMA granted approval in May 2018, for the treatment of high-grade, BRCA mutation +ve cancers of the ovary, fallopian tubes and peritoneum that has been responsive to previous platinum-based chemotherapy [4].
Mechanism Of Action and Pharmacodynamic Effects
PARP-1 (poly(ADP-ribose) polymerase 1) inhibitors enhance the efficacy of drugs/therapies which cause DNA damage (eg alkylating agents such as temozolomide , topoisomerase poisons such as topotecan and irinotecan and ionizing radiation) [1,3]. This action helps to promote cancer cell death, by preventing the DNA repair which is required for cell survival. Cells with mutations in other DNA repair enzymes such as BRCA become more dependent on PARP for DNA repair. In such malignant cells, inhibition of PARP may therefore result in cell death due to accumulated therapy-induced DNA damage.
External links