Rucaparib camsylateProduct ingredient for Rucaparib

Name
Rucaparib camsylate
Drug Entry
Rucaparib

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 9.

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.

Accession Number
DBSALT001982
Structure
Thumb
Synonyms
Not Available
External IDs
C0-338 / PF-1367338-BW
UNII
41AX9SJ8KO
CAS Number
1859053-21-6
Weight
Average: 555.67
Monoisotopic: 555.220320544
Chemical Formula
C29H34FN3O5S
InChI Key
INBJJAFXHQQSRW-STOWLHSFSA-N
InChI
InChI=1S/C19H18FN3O.C10H16O4S/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;1-9(2)7-3-4-10(9,8(11)5-7)6-15(12,13)14/h2-5,8-9,21,23H,6-7,10H2,1H3,(H,22,24);7H,3-6H2,1-2H3,(H,12,13,14)/t;7-,10-/m.1/s1
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; [(1S,4R)-7,7-dimethyl-2-oxobicyclo[2.2.1]heptan-1-yl]methanesulfonic acid
SMILES
CC1(C)[C@@H]2CC[C@@]1(CS(O)(=O)=O)C(=O)C2.CNCC1=CC=C(C=C1)C1=C2CCNC(=O)C3=C2C(N1)=CC(F)=C3
External Links
ChemSpider
57643660
ChEBI
134692
ChEMBL
CHEMBL3833368
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 Count5ChemAxon
Refractivity92.91 m3·mol-1ChemAxon
Polarizability35.15 Å3ChemAxon
Number of Rings6ChemAxon
Bioavailability1ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon