General
Preferred name
RUCAPARIB
Synonyms
AG014699 (monocamsylate) ()
PF-01367338 (monocamsylate) ()
AG-014699 (phosphate) ()
PF-01367338 (phosphate) ()
AG014699 ()
PF-01367338 ()
AG-014699 ()
PF-01367338 phosphate ()
AG-014699 phosphate ()
AG-14447 ()
RUCAPARIB PHOSPHATE ()
RUCAPARIB CAMSYLATE ()
AG 014699 ()
A-6053 ()
S1098 ()
Rucaparib (monocamsylate) ()
Rucaparib (phosphate) ()
Rucaparib (AG-014699) phosphate ()
Rubraca, AG014699, PF01367338 ()
Rubraca, AG014699 Camsylate, PF01367338 Camsylate ()
AG-14699 ()
PF01367338 ()
CO-338 ()
Rubraca ()
C0-338 ()
PF-1367338-BW ()
Rucaparib (camsylate) ()
P&D ID
PD018527
CAS
459868-92-9
283173-50-2
1859053-21-6
Tags
available
drug
drug candidate
Approved by
FDA
EMA
First approval
2016
Drug indication
Ovarian cancer
Drug Status
approved
investigational
Max Phase
1.0
4.0
Probe control
Probe control not defined
Orthogonal probes
0
No orthogonal probes found
Similar probes
0
No structurally similar probes found
Structure
P&D probe-likeness score
Structure formats
[[ format ]]
[[ compound[format === 'MOL' ? 'molblock' : format.toLowerCase()] ]]
Description
(extracted from source data)
PHARMACODYNAMICS
Rucaparib has been shown to decrease tumor growth in mouse xenograft models of human cancer with or without deficiencies in BRCA [FDA 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) [FDA Label].
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 hâ
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 [FDA Label].
DESCRIPTION
Rucaparib is an orally active poly(ADP-ribose)polymerase (PARP) inhibitor with anti-cancer activity . It was developed by Clovis Oncology.
PARP inhibitors are known to enhance efficacy of anti-cancer therapies such as DNA alkylating agents, topoisomerase I poisons, and ionizing radiation.
Note that in the Thomas et al. paper , AG014699 refers to the phosphate salt and AG14447 to the parent molecule.
Rucaparib was accepted for FDA priority review for the treatment of advanced ovarian cancer harbouring mutant BRCA (August 2016).
Note: was the first PARP inhibitor to be approved for clinical use. (GtoPdb)
PARP inhibitors are known to enhance efficacy of anti-cancer therapies such as DNA alkylating agents, topoisomerase I poisons, and ionizing radiation.
Note that in the Thomas et al. paper , AG014699 refers to the phosphate salt and AG14447 to the parent molecule.
Rucaparib was accepted for FDA priority review for the treatment of advanced ovarian cancer harbouring mutant BRCA (August 2016).
Note: was the first PARP inhibitor to be approved for clinical use. (GtoPdb)
MOA
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 [A18745]. When PARP is inhibited, single-strand breaks become double-strand breaks, which are typically repaired via homologous recombination [A18745]. 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 [FDA 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 [A31354]. 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 [A31354].
DESCRIPTION
Rucaparib Phosphate is a selective PARP inhibitor that suppresses the PARP1-mediated DNA repair via binding to PARP1 (Ki = <5 nM). It can be used to sensitize cancer cells to chemotherapy as an antineoplastic agent.
(BOC Sciences Bioactive Compounds)
DESCRIPTION
Potent irreversible pan ErbB inhibitor
(Tocris Bioactive Compound Library)
[[ p.pathway_name ]]
[[ compound.targets[tid].gene_name ]]
Cell lines
300
Organisms
0
Compound Sets
28
BOC Sciences Bioactive Compounds
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CZ-OPENSCREEN Bioactive Library
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DrugMAP Approved Drugs
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Welcome Trust Cancer Drugs
[[ a.name ]]
[[ ligand_id ]]
free of charge
External IDs
75
Molecular Weight
323.14
Hydrogen Bond Acceptors
2
Hydrogen Bond Donors
3
Rotatable Bonds
3
Ring Count
4
Aromatic Ring Count
3
cLogP
2.98
TPSA
56.92
Fraction CSP3
0.21
Chiral centers
0.0
Largest ring
7.0
QED
0.69
Structural alerts
0
No structural alerts detected
Related compounds
Custom attributes
(extracted from source data)
Pathway
Genome integrity
Chromatin/Epigenetic
DNA Damage/DNA Repair
Cell Cycle/DNA Damage
Epigenetics
Target
PARP1, PARP2
PARP
PARP1
PARP1 inhibitor
Primary Target
Poly(ADP-ribose) Polymerase
MOA
Inhibitor
Poly(ADP-ribose)polymerase-1 (PARP-1) Inhibitors
Poly(ADP-ribose)polymerase-2 (PARP-2) Inhibitors
DNA Repair Inhibitors
PARP inhibitor
Member status
member
Source data
