Home DNA Damage/DNA Repair PARP Inhibitor Rucaparib phosphate

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Rucaparib phosphate PARP Inhibitor

Kat.-Nr.: S1098

Rucaparib phosphate ist ein Inhibitor von PARP mit einem Ki von 1,4 nM für PARP1 in einem zellfreien Assay und zeigt auch eine Bindungsaffinität zu acht anderen PARP-Domänen. Phase 3.
Rucaparib phosphate PARP Inhibitor Chemical Structure

Chemische Struktur

Molekulargewicht: 421.36

Springe zu

Qualitätskontrolle (Quality Control)

Charge: Reinheit: 99.89%
99.89

Zellkultur, Behandlung & Arbeitskonzentration
(Cell Culture, Treatment & Working Concentration)

Zelllinien Assay-Typ Konzentration Inkubationszeit Formulierung Aktivitätsbeschreibung PMID
BT-474 Function Assay 0.1/1/500/1000 nM inhibits PARP activity at starting concerntration of 500 nM 25128455
BT474 Growth Inhibition Assay 500 nM 10–15 d reduces cell growth in the four lines and significantly 25128455
SKBR3 Growth Inhibition Assay 500 nM 10–15 d reduces cell growth in the four lines and significantly 25128455
AU565 Growth Inhibition Assay 500 nM 10–15 d reduces cell growth in the four lines and significantly 25128455
EFM192A Growth Inhibition Assay 500 nM 10–15 d reduces cell growth in the four lines and significantly 25128455
MDA-MB-231 Function Assay 10/20/40 μM 24 h increases p-AKT levels in a dose-dependent manner 24420152
MDA-MB-231 Cell Viability Assay 0.1-40 μM 24 h IC50 = 17.77 μM 24420152
MDA-MB-231 Apoptosis Assay 10/20/40 μM 24 h induces apoptosis dose dependently 24420152
MDA-MB-231 Growth Inhibition Assay 10/20/40 μM 24 h blocks cell cycle progression in G2/M phase 24420152
H460 Growth Inhibition Assay 400 nM 24 h increases cellular radiosensitivity 24411611
A549  Growth Inhibition Assay 400 nM 24 h increases cellular radiosensitivity 24411611
DT40 Growth Inhibition Assay IC50=21 nM 24356813
DU145 Growth Inhibition Assay IC50=18 nM 24356813
COLO704 Growth Inhibition Assay IC50=2.52 ± 0.67 μM 23729402
OVMANAb Growth Inhibition Assay IC50=2.58 ± 0.38 μM 23729402
OV177 Growth Inhibition Assay IC50=2.78 ± 0.71 μM 23729402
OAW28 Growth Inhibition Assay IC50=3.61 ± 0.28 μM 23729402
OVSAHO Growth Inhibition Assay IC50=3.64 ± 0.33 μM 23729402
OVKATE Growth Inhibition Assay IC50=3.64 ± 1.79 μM 23729402
OVCAR3 Growth Inhibition Assay IC50=3.74 ± 0.40 μM 23729402
PEO14 Growth Inhibition Assay IC50=3.84 ± 0.76 μM 23729402
A2780 Growth Inhibition Assay IC50=3.94 ± 0.25 μM 23729402
OVTOKO Growth Inhibition Assay IC50=4.14 ± 1.53 μM 23729402
KURAMOCHIb Growth Inhibition Assay IC50=4.34 ± 0.29 μM 23729402
TOV21G Growth Inhibition Assay IC50=5.07 ± 1.30 μM 23729402
OVISE Growth Inhibition Assay IC50=5.68 ± 0.23 μM 23729402
KK Growth Inhibition Assay IC50=6.15 ± 1.42 μM 23729402
RMUGS Growth Inhibition Assay IC50=7.03 ± 1.83 μM 23729402
PEO6 Growth Inhibition Assay IC50=7.06 ± 0.74 μM 23729402
OVCA429 Growth Inhibition Assay IC50=8.29 ± 1.64 μM 23729402
OV167 Growth Inhibition Assay IC50=8.33 ± 1.18 μM 23729402
RMG1 Growth Inhibition Assay IC50=9.32 ± 2.36 μM 23729402
OVCAR5 Growth Inhibition Assay IC50=9.50 ± 2.59 μM 23729402
EFO21 Growth Inhibition Assay IC50=9.92 ± 1.87 μM 23729402
ES2 Growth Inhibition Assay IC50=10.12 ± 1.23 μM 23729402
Tyk-nu Growth Inhibition Assay IC50=10.20 ± 1.12 μM 23729402
CAOV3 Growth Inhibition Assay IC50=10.37 ± 0.87 μM 23729402
OV207 Growth Inhibition Assay IC50=12.27 ± 0.32 μM 23729402
HEY Growth Inhibition Assay IC50=13.01 ± 0.75 μM 23729402
DOV13 Growth Inhibition Assay IC50>15 μM 23729402
EFO27 Growth Inhibition Assay IC50>15 μM 23729402
HEY C2 Growth Inhibition Assay IC50>15 μM 23729402
KOC-7cc Growth Inhibition Assay IC50>15 μM 23729402
MCASb Growth Inhibition Assay IC50>15 μM 23729402
OAW42 Growth Inhibition Assay IC50>15 μM 23729402
OV2008 Growth Inhibition Assay IC50>15 μM 23729402
OV90 Growth Inhibition Assay IC50>15 μM 23729402
OVCA420b Growth Inhibition Assay IC50>15 μM 23729402
OVCA432 Growth Inhibition Assay IC50>15 μM 23729402
PEA2 Growth Inhibition Assay IC50>15 μM 23729402
SKOV3 Growth Inhibition Assay IC50>15 μM 23729402
TOV112D Growth Inhibition Assay 0-3 μM IC50>15 μM 23729402
C4-2 Growth Inhibition Assay 0-3 μM 14 d DMSO decreases colony number dose dependently 23565244
PC3 Growth Inhibition Assay 0-3 μM 14 d DMSO decreases colony number dose dependently 23565244
DU145 Growth Inhibition Assay 0-3 μM 14 d DMSO decreases colony number dose dependently 23565244
VCaP  Growth Inhibition Assay 0-3 μM 14 d DMSO decreases colony number dose dependently 23565244
LNCaP  Growth Inhibition Assay 0-3 μM 14 d DMSO decreases colony number dose dependently 23565244
MDA-MB-468 Cell Viability Assay IC50=9.7 μM 22678161
MDA-MB-231 Cell Viability Assay IC50=13 μM 22678161
Cal-51 Cell Viability Assay IC50=8.6 μM 22678161
LoVo Function assay 30 mins Inhibition of PARP in human LoVo cells assessed as inhibition of poly(ADP)-ribose polymerization for 30 mins by fluorescence assay, EC50 = 0.00469 μM. 26652717
MX1 Cytotoxicity assay Cytotoxicity against BRCA1-deficient human MX1 cells, EC50 = 0.0053 μM. 26652717
Rosetta2 (DE3) Function assay Inhibition of human N-terminal 6xhis-tagged ARTD6 (873 to 1161) expressed in Escherichia coli Rosetta2 (DE3) cells using NAD+ as substrate by fluorescence assay, IC50 = 0.014 μM. 24900770
Rosetta2 (DE3) Function assay Inhibition of human 6xhis-tagged ARTD5 (1030 to 1317) expressed in Escherichia coli Rosetta2 (DE3) cells using NAD+ as substrate by fluorescence assay, IC50 = 0.025 μM. 24900770
LoVo Cytotoxicity assay 0.4 uM 5 days Potentiation of temozolomide-induced cytotoxicity in human LoVo cells assessed as temozolomide GI50 at 0.4 uM after 5 days by Celltiter-Glo assay, GI50 = 0.144 μM. 26652717
Capan1 Cytotoxicity assay Cytotoxicity against BRCA2-deficient human Capan1 cells, EC50 = 0.609 μM. 26652717
MDA-MB-436 Anticancer assay 96 hrs Anticancer activity against human BRCA1-deficient MDA-MB-436 cells after 96 hrs by MTT assay, CC50 = 3 μM. 26342868
OVCAR3 Antiproliferative assay 24 hrs Antiproliferative activity against human OVCAR3 cells after 24 hrs by MTT assay, IC50 = 3.31 μM. 29456106
MRC5 Cytotoxicity assay Cytotoxicity against human MRC5 cells, EC50 = 8.53 μM. 26652717
MCF7 Anticancer assay 96 hrs Anticancer activity against human MCF7 cells after 96 hrs by MTT assay, CC50 = 19.47 μM. 26342868
A673 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for A673 cells 29435139
A673 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for A673 cells) 29435139
Rh41 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for Rh41 cells 29435139
SK-N-MC qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for SK-N-MC cells 29435139
TC32 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for TC32 cells 29435139
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Chemische Informationen, Lagerung & Stabilität (Chemical Information, Storage & Stability)

Molekulargewicht 421.36 Formel

C19H18FN3O.H3PO4

 Lagerung (Ab dem Eingangsdatum)
CAS-Nr. 459868-92-9 SDF herunterladen Lagerung von Stammlösungen

Synonyme AG-014699 phosphate, PF-01367338 phosphate Smiles CNCC1=CC=C(C=C1)C2=C3CCNC(=O)C4=C3C(=CC(=C4)F)N2.OP(=O)(O)O

Löslichkeit (Solubility)

In vitro
Charge:

DMSO : 85 mg/mL (201.72 mM)
(Feuchtigkeitskontaminiertes DMSO kann die Löslichkeit verringern. Verwenden Sie frisches, wasserfreies DMSO.)

Water : 7 mg/mL

Ethanol : Insoluble

Molaritätsrechner

Masse Konzentration Volumen Molekulargewicht
Verdünnungsrechner Molekulargewichtsrechner

In vivo
Charge:

In-vivo-Formulierungsrechner (Klare Lösung)

Schritt 1: Geben Sie die untenstehenden Informationen ein (Empfohlen: Ein zusätzliches Tier zur Berücksichtigung von Verlusten während des Experiments)

mg/kg g μL

Schritt 2: Geben Sie die In-vivo-Formulierung ein (Dies ist nur der Rechner, keine Formulierung. Bitte kontaktieren Sie uns zuerst, wenn es im Abschnitt "Löslichkeit" keine In-vivo-Formulierung gibt.)

% DMSO % % Tween 80 % ddH2O
%DMSO %

Berechnungsergebnisse:

Arbeitskonzentration: mg/ml;

Methode zur Herstellung der DMSO-Stammlösung: mg Wirkstoff vorgelöst in μL DMSO ( Konzentration der Stammlösung mg/mL, Bitte kontaktieren Sie uns zuerst, wenn die Konzentration die DMSO-Löslichkeit der Wirkstoffcharge überschreitet. )

Methode zur Herstellung der In-vivo-Formulierung: Nehmen Sie μL DMSO Stammlösung, dann hinzufügenμL PEG300, mischen und klären, dann hinzufügenμL Tween 80, mischen und klären, dann hinzufügen μL ddH2O, mischen und klären.

Methode zur Herstellung der In-vivo-Formulierung: Nehmen Sie μL DMSO Stammlösung, dann hinzufügen μL Maisöl, mischen und klären.

Hinweis: 1. Bitte stellen Sie sicher, dass die Flüssigkeit klar ist, bevor Sie das nächste Lösungsmittel hinzufügen.
2. Achten Sie darauf, das/die Lösungsmittel der Reihe nach hinzuzufügen. Sie müssen sicherstellen, dass die bei der vorherigen Zugabe erhaltene Lösung eine klare Lösung ist, bevor Sie mit der Zugabe des nächsten Lösungsmittels fortfahren. Physikalische Methoden wie Vortex, Ultraschall oder ein heißes Wasserbad können zur Unterstützung des Lösens verwendet werden.

Wirkmechanismus (Mechanism of Action)

Merkmale
The first PARP inhibitor used in clinical trials combined with temozolomide.
Targets/IC50/Ki
PARP
(Cell-free assay)
1.4 nM(Ki)
In vitro
Rucaparib is a potent inhibitor of purified full-length human PARP-1 and shows higher inhibition of cellular PARP in LoVo and SW620 cells. Besides, Rucaparib binds detectably to eight other PARP domains, including PARP2, 3, 4, 10, 15, 16, TNKS1 and TNKS2. The radio-sensitization by Rucaparib is due to downstream inhibition of activation of NF-κB, and is independent of SSB repair inhibition. Rucaparib could target NF-κB activated by DNA damage and overcome toxicity observed with classical NF-κB inhibitors without compromising other vital inflammatory functions. Rucaparib inhibits PARP-1 activity by 97.1% at a concentration of 1 μM in permeabilised D283Med cells.
Kinase-Assay
Ki-Bestimmung
Die Hemmung der humanen rekombinanten PARP-1 in voller Länge durch den Einbau von [32P]NAD+ wird gemessen. Das in säureunlösliches Material eingebaute [32P]ADP-Ribose wird mit einem PhosphorImager quantifiziert. Ki wird mittels nichtlinearer Regressionsanalyse berechnet.
In vivo
Rucaparib is not toxic but significantly enhances temozolomide-induced TGD in the DNA repair protein-competent D384Med xenografts. Pharmacokinetics studies also show that Rucaparib is detected in the brain tissue, which indicates that Rucaparib has potential in intra-cranial malignancy therapy. Rucaparib significantly potentiates the cytotoxicity of topotecan and temozolomide in NB-1691, SH-SY-5Y, and SKNBE (2c) cells. Rucaparib enhances the antitumor activity of temozolomide and indicates complete and sustained tumor regression in NB1691 and SHSY5Y xenografts.
Literatur
  • [4] https://pubmed.ncbi.nlm.nih.gov/20978505/
  • [5] https://pubmed.ncbi.nlm.nih.gov/19174487/

Anwendungen (Applications)

Methoden Biomarker Bilder PMID
Western blot PAR BRCA1
S1098-WB1
27960087
Growth inhibition assay Cell viability
S1098-viability1
31119062
Immunofluorescence α-tubulin PAR γH2AX 53BP1
S1098-IF1
30589644

Klinische Studieninformationen (Clinical Trial Information)

(Daten von https://clinicaltrials.gov, aktualisiert am 2026-07-29)

NCT-Nummer Rekrutierung Erkrankungen Sponsor/Kooperationspartner Startdatum Phasen
NCT03899155 RECRUITING
Cancer
Bristol-Myers Squibb
 2019-08-09 PHASE2
NCT03768063 ACTIVE_NOT_RECRUITING
Cancer
Hoffmann-La Roche
 2019-02-28 PHASE3
NCT02925234 RECRUITING
Cancer; Tumors; Neoplasm; Neoplasia
The Netherlands Cancer Institute
 2016-08 PHASE2
NCT04455750 ACTIVE_NOT_RECRUITING
Castration-Resistant Prostate Carcinoma; Metastatic Prostate Adenocarcinoma; Stage IV Prostate Cancer AJCC v8; Stage IVA Prostate Cancer AJCC v8; Stage IVB Prostate Cancer AJCC v8
Alliance for Clinical Trials in Oncology
 2021-10-14 PHASE3
NCT04253262 ACTIVE_NOT_RECRUITING
Metastatic Castration-resistant Prostate Cancer
Brown University
 2020-04-03 PHASE1; PHASE2
NCT04624178 ACTIVE_NOT_RECRUITING
Leiomyosarcoma
Memorial Sloan Kettering Cancer Center
 2020-11-05 PHASE2