Rucaparib (AG-014699)

Alias: AG014699; PF-01367338; AG 14447; AG 014699; PF 01367338; AG-014699,PF01367338; AG-14447; AG14447; Trade name: Rubraca

Cat No.:V3935 Purity: ≥98%

COA Product Data Instructions for use SDS

Rucaparib (formerly known as AG-14447; AG-014699; PF-01367338;Rubraca) is an inhibitor of PARP [(poly(ADP-Ribose) polymerase)] with anticancer effects.

Rucaparib (AG-014699) Chemical Structure CAS No.: 283173-50-2
Product category: PARP

This product is for research use only, not for human use. We do not sell to patients.

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Top Publications Citing lnvivochem Products

Nature 2021, 597(7874):119-125.

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Cancer Cell 2021,39(4):529-547.e7.

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Immunity 2023,56(3):620-634.e11.

J Am Chem Soc 2022,144:21831-21836.

Cell 2020,183:1202-1218.e25.

Science Adv 2022:8,eabm9427.

Nature 2021,597(7874):119-125.

Cell 2020,183:1202-1218.e25.

PNAS Nexus 2022,1(3):pgac063.

ACS Nano 2023,17(10):9110-9125.

Biomaterial 2023 Sep16:302:122333.

Purity & Quality Control Documentation

Current batch：

Purity: ≥98%

COA

MSDS

Instructions

Product Description
Bioactivity & Protocols
Physicochemical Properties
Solubility Data
Calculators
Clinical Trial Information
Biological Data

Product Description

Rucaparib (formerly known as AG-14447; AG-014699; PF-01367338; Rubraca) is an inhibitor of PARP [ (poly(ADP-Ribose) polymerase)] with anticancer effects. In a cell-free assay, it inhibits PARP1 with a Ki of 1.4 nM. The FDA approved rucaparib in 2016 for the treatment of ovarian cancer in female patients. Rucaparib binds specifically to PARP1 and prevents PARP1 from repairing damaged DNA, which increases the number of breaks in DNA strands and encourages apoptosis and genomic instability. This could reverse tumor cell resistance to chemotherapy and radiation therapy and increase the cytotoxicity of agents that damage DNA.

Biological Activity I Assay Protocols (From Reference)

Targets

PARP-1 ( Ki = 1.4 nM ); PARP-2; PARP-3

ln Vitro

Rucaparib (AG014699) is a potential AG14644 N-demethylation metabolite[1].
Rucaparib (0.1, 1, 10, 100 μM; 24 hours) is cytotoxic; in Capan-1 (BRCA2 mutant) cells, its LC50 is 5 μM, while in MX-1 (BRCA1 mutant) cells, it is only 100 nM[2].
Rucaparib causes radiosensitization independent of SSB repair inhibition, as it inhibits NF-κB activation downstream. Without impairing other essential inflammatory functions, rucaparib can target NF-κB that is activated by DNA damage and overcome the toxicity seen with classical NF-κB inhibitors[5].
Rucaparib inhibits PARP-1 activity in permeabilized D283Med cells by 97.1% at a concentration of 1 μM[6].

ln Vivo

Rucaparib (AG014699) and AG14584 greatly heighten the toxicity of temozolomide. The amount of body weight lost when using Temozolomide is greatly increased by Rucaparib (1 mg/kg). A 50% increase in the temozolomide-induced tumor growth delay is observed when rucaparib (0.1 mg/kg) is administered[1].
Rucaparib (10 mg/kg for intraperitoneal injection or 50–150 mg/kg for parenteral administration; five days a week for six weeks) dramatically slows tumor growth and causes one complete tumor regression and two persistent partial tumor regressions[2].
Rucaparib has the strongest antitumor effect with three full regressions at 150 mg/kg p.o. administered once or three times a week for six weeks[2].
Rucaparib improves temozolomide's antitumor activity and shows full and long-lasting tumor regression in NB1691 and SHSY5Y xenografts[6].

Cell Assay

The MTT assay is used to measure cell proliferation. In 96-well plates, the cells are seeded at a density of 5×10³ cells/ml in a volume of 200 μl/well. The following day, DMSO, BKM120, or rucaparib are added in varying concentrations to the cells. Each well receives 20 μl of MTT (5 mg/ml) after four days. Following an additional 4-hour incubation period at 37 °C, the absorbance at 490 nm is determined. CalcuSyn software is used to analyze data from growth inhibitory experiments in order to ascertain the effect of drug combinations. Next, combination indexes (CI) are computed.

Animal Protocol

Dissolved in saline; 1 mg/kg; One or four daily by i.p.

CD-1 nude mice bearing established D283Med xenografts

References

[1]. Preclinical selection of a novel poly(ADP-ribose) polymerase inhibitor for clinical trial. Mol Cancer Ther, 2007, 6(3), 945-956.

[2]. Tumour cell retention of rucaparib, sustained PARP inhibition and efficacy of weekly as well as daily schedules. Br J Cancer. 2014 Apr 15;110(8):1977-84.

[3]. Inhibition of poly(ADP-ribose) polymerase-1 enhances temozolomide and topotecan activity against childhood neuroblastoma. Clin Cancer Res, 2009, 15(4), 1241-1249.

[4]. Hexose-6-phosphate dehydrogenase blockade reverses prostate cancer drug resistance in xenograft models by glucocorticoid inactivation. Sci Transl Med. 2021 May 26;13(595):eabe8226.

[5]. NF-κB mediates radio-sensitization by the PARP-1 inhibitor, AG-014699. Oncogene, 2012, 31(2), 251-264.

[6]. Rucaparib: A Review in Ovarian Cancer. Target Oncol. 2019 Apr;14(2):237-246.

These protocols are for reference only. InvivoChem does not independently validate these methods.

Physicochemical Properties

Molecular Formula

C19H18FN3O

Molecular Weight

323.37

Exact Mass

323.14

Elemental Analysis

C, 70.57; H, 5.61; F, 5.88; N, 12.99; O, 4.95

CAS #

283173-50-2

Related CAS #

1859053-21-6 (camsylate); 459868-92-9 (phosphate); 283173-50-2

Appearance

Yellow solid powder

SMILES

CNCC1=CC=C(C=C1)C2=C3CCNC(=O)C4=C3C(=CC(=C4)F)N2

InChi Key

HMABYWSNWIZPAG-UHFFFAOYSA-N

InChi Code

InChI=1S/C19H18FN3O/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/h2-5,8-9,21,23H,6-7,10H2,1H3,(H,22,24)

Chemical Name

6-fluoro-2-[4-(methylaminomethyl)phenyl]-3,10-diazatricyclo[6.4.1.04,13]trideca-1,4,6,8(13)-tetraen-9-one

Synonyms

AG014699; PF-01367338; AG 14447; AG 014699; PF 01367338; AG-014699,PF01367338; AG-14447; AG14447; Trade name: Rubraca

HS Tariff Code

2934.99.9001

Storage

Powder -20°C 3 years

4°C 2 years

In solvent -80°C 6 months

-20°C 1 month

Shipping Condition

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Solubility Data

Solubility (In Vitro)

DMSO: ~10 mM

Water: <1 mg/mL

Ethanol: <1 mg/mL

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (7.73 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

Solubility in Formulation 2: ≥ 2.5 mg/mL (7.73 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.5 mg/mL (7.73 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

Solubility in Formulation 4: 30% propylene glycol, 5% Tween 80, 65% D5W: 30mg/mL

(Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	3.0924 mL	15.4622 mL	30.9243 mL
	5 mM	0.6185 mL	3.0924 mL	6.1849 mL
	10 mM	0.3092 mL	1.5462 mL	3.0924 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.

Calculator

Mass

Concentration

Volume

Molecular Weight*

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Molarity Calculator allows you to calculate the mass, volume, and/or concentration required for a solution, as detailed below:

Calculate the Mass of a compound required to prepare a solution of known volume and concentration
Calculate the Volume of solution required to dissolve a compound of known mass to a desired concentration
Calculate the Concentration of a solution resulting from a known mass of compound in a specific volume

See Example

An example of molarity calculation using the molarity calculator is shown below:
What is the mass of compound required to make a 10 mM stock solution in 5 ml of DMSO given that the molecular weight of the compound is 350.26 g/mol?

Enter 350.26 in the Molecular Weight (MW) box
Enter 10 in the Concentration box and choose the correct unit (mM)
Enter 5 in the Volume box and choose the correct unit (mL)
Click the “Calculate” button
The answer of 17.513 mg appears in the Mass box. In a similar way, you may calculate the volume and concentration.

Concentration (Start)

Volume (Start)

Concentration (End)

Volume (End)

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Dilution Calculator allows you to calculate how to dilute a stock solution of known concentrations. For example, you may Enter C1, C2 & V2 to calculate V1, as detailed below:

What volume of a given 10 mM stock solution is required to make 25 ml of a 25 μM solution?
Using the equation C1V1 = C2V2, where C1=10 mM, C2=25 μM, V2=25 ml and V1 is the unknown:

Enter 10 into the Concentration (Start) box and choose the correct unit (mM)
Enter 25 into the Concentration (End) box and select the correct unit (mM)
Enter 25 into the Volume (End) box and choose the correct unit (mL)
Click the “Calculate” button
The answer of 62.5 μL (0.1 ml) appears in the Volume (Start) box

Molecular formula

Total molecular weight

g/mol

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Molecular Weight Calculator allows you to calculate the molar mass and elemental composition of a compound, as detailed below:

Note: Chemical formula is case sensitive: C12H18N3O4 c12h18n3o4
Instructions to calculate molar mass (molecular weight) of a chemical compound:

To calculate molar mass of a chemical compound, please enter the chemical/molecular formula and click the “Calculate’ button.

Definitions of molecular mass, molecular weight, molar mass and molar weight:

Molecular mass (or molecular weight) is the mass of one molecule of a substance and is expressed in the unified atomic mass units (u). (1 u is equal to 1/12 the mass of one atom of carbon-12)
Molar mass (molar weight) is the mass of one mole of a substance and is expressed in g/mol.

Volume (to add to vial)

Mass (in vial)

Desired Reconstitution Concentration

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Reconstitution Calculator allows you to calculate the volume of solvent required to reconstitute your vial.

Enter the mass of the reagent and the desired reconstitution concentration as well as the correct units
Click the “Calculate” button
The answer appears in the Volume (to add to vial) box

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal to make allowance for loss during the experiment)

Dosage mg/kg

Average weight of animals g

Dosing volume per animal μL

Number of animals

Step 2: Enter in vivo formulation (This is only a calculator, not the exact formulation for a specific product. Please contact us first if there is no in vivo formulation in the solubility section.)

% DMSO

% Tween 80

% ddH₂O

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Calculation results

Working concentration： mg/mL；

Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.

Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH₂O，mix and clarify.

Note： (1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.

Clinical Trial Information

NCT Number	Recruitment	interventions	Conditions	Sponsor/Collaborators	Start Date	Phases
NCT03413995	Recruiting	Drug: Rucaparib	Prostate Cancer Metastatic	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	September 10, 2018	Phase 2
NCT03462212	Recruiting	Drug: Rucaparib Drug: Paclitaxel	Advanced (Stage IIIB-C-IV) Ovarian, Primary Peritoneal and Fallopian Tube Cancer	Fondazione Policlinico Universitario Agostino Gemelli IRCCS	March 17, 2021	Phase 1 Phase 2
NCT04826198	Recruiting	Drug: Rucaparib Drug: Olaparib	Ovarian Cancer	Gustave Roussy, Cancer Campus, Grand Paris	October 5, 2020	Phase 1 Phase 2

Biological Data

AG-014699 inhibits Single strand break (SSB) repair to a similar extent regardless of cellular NF-κB status.Oncogene, 2012, 31(2), 251-264.