Rucaparib phosphate

Catalog No.S1098 Batch:S109813

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Technical Data

Formula

C19H18FN3O.H3PO4
Molecular Weight 421.36 CAS No. 459868-92-9
Solubility (25°C)* In vitro DMSO 84 mg/mL (199.35 mM)
Water 6 mg/mL (14.23 mM)
Ethanol Insoluble
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

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Biological Activity

Description Rucaparib phosphate is an inhibitor of PARP with Ki of 1.4 nM for PARP1 in a cell-free assay, also showing binding affinity to eight other PARP domains. Phase 3.
Targets
PARP [1]
(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. [1] [2] 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. [3] Rucaparib inhibits PARP-1 activity by 97.1% at a concentration of 1 μM in permeabilised D283Med cells. [4]
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. [4] 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. [5]
Features The first PARP inhibitor used in clinical trials combined with temozolomide.

Protocol (from reference)

Kinase Assay:[1]
  • Ki Determination

    Inhibition of human full-length recombinant PARP-1 by [32P]NAD+ incorporation is measured. The [32P]ADP-ribose incorporated into acid insoluble material is quantified using a PhosphorImager. Ki is calculated by nonlinear regression analysis.
Cell Assay:[4]
  • Cell lines

    D425Med, D283Med and D384Med cells

  • Concentrations

    0.4 μM

  • Incubation Time

    3 or 5 days

  • Method

    Medulloblastoma cell lines are seeded in 96-well plates at a density of 1 × 103, 3 × 103 and 3 × 103, respectively. At 24 hours (D384Med) or 48 hours (D283Med and D425Med) after seeding, the cells are exposed to various concentrations of temozolomide in the presence or absence of 0.4 μM Rucaparib. After 3 days (D425Med and D384Med) or 5 days (D283Med) of culture, cell viability is evaluated by a XTT cell proliferation kit assay. Cell growth is expressed as a percentage in relation to DMSO or 0.4 μM Rucaparib-alone controls. The concentration of temozolomide, alone or in combination with Rucaparib that inhibited growth by 50% (GI50) is calculated. The potentiation factor 50 (PF50) is defined as the ratio of the GI50 of temozolomide in the presence of Rucaparib to the GI50 of temozolomide alone.
Animal Study:[4]
  • Animal Models

    CD-1 nude mice bearing established D283Med xenografts

  • Dosages

    1 mg/kg

  • Administration

    One or four daily by i.p.

Customer Product Validation

Data from [Data independently produced by Eur J Cancer, 2014, 50(15), 2725-34]

Data from [Data independently produced by Eur J Cancer, 2014, 50(15), 2725-34]

Data from [Data independently produced by Oral Oncol, 2014, 50(9), 825-31]

Data from [Data independently produced by Urol Oncol, 2014, 32(5), 720-6]

Selleck's Rucaparib phosphate has been cited by 132 publications

Human Fallopian Tube-Derived Organoids with TP53 and RAD51D Mutations Recapitulate an Early Stage High-Grade Serous Ovarian Cancer Phenotype In Vitro [ Int J Mol Sci, 2024, 25(2)886] PubMed: 38255960
CK2-HTATSF1-TOPBP1 signaling axis modulates tumor chemotherapy response [ J Biol Chem, 2024, 300(6):107377] PubMed: 38762174
BRCA2 Germline Mutations Identify Gastric Cancers Responsive to PARP Inhibitors [ Cancer Res, 2023, 83(10):1699-1710] PubMed: 37129948
Pharmacological depletion of RNA splicing factor RBM39 by indisulam synergizes with PARP inhibitors in high-grade serous ovarian carcinoma [ Cell Rep, 2023, 42(10):113307] PubMed: 37858464
The Sensitization of Triple-Negative Breast Cancers to Poly ADP Ribose Polymerase Inhibition Independent of BRCA1/2 Mutation Status by Chemically Modified microRNA-489 [ Cells, 2023, 13(1)49] PubMed: 38201253
Venadaparib Is a Novel and Selective PARP Inhibitor with Improved Physicochemical Properties, Efficacy, and Safety [ Mol Cancer Ther, 2023, 22(3):333-342] PubMed: 36808277
Establishment and Molecular Characterization of an In Vitro Model for PARPi-Resistant Ovarian Cancer [ Cancers (Basel), 2023, 15(15)3774] PubMed: 37568590
Slow Dissociation from the PARP1-HPF1 Complex Drives Inhibitor Potency [ Biochemistry, 2023, 62(16):2382-2390] PubMed: 37531469
Histone H1. 2 Dependent Translocation of Poly (ADP-ribose) Initiates Parthanatos [ bioRxiv, 2023, 10.1101/2023.06.18.545460] PubMed: none
A site-specific analysis of the ADP-Ribosylome unveils Homogeneous DNA Damage-Induced Serine ADP-Ribosylation across wild-type and BRCA-mutant Breast [ bioRxiv, 2023, 10.1101/2023.12.15.571635] PubMed: none

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

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