Rucaparib (AG-014699 , PF-01367338)

Validation & Quality Control

Product Citations(3)

Nature, 2011, 470(7334), 419-423

Cancer Lett, 2012, 319(2), 232-241

Nucl Med Commun, 2011, 32(11):1046-51

Customer Reviews(2) in vivo invitation

Quality Control & MSDS

Related Compound Libraries

Rucaparib (AG-014699 , PF-01367338) is available in the following compound libraries:

Cambridge Cancer Compound Library(96-well) Chemical Library (96-well) Inhibitor Library (96-well)

Product Information

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Research Area
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Dr. Antonino Maria Sparta demonstrates a breakthrough in leukemia research by utilizing two inhibitors produced by Selleck Chemicals.

Cat.No.	Product Name	Solubility (25°C)
S1060	Olaparib (AZD2281)	<1 mg/mL	87 mg/mL	<1 mg/mL
S1004	ABT-888 (Veliparib)	<1 mg/mL	17 mg/mL	<1 mg/mL
S1098	Rucaparib (AG-014699 , PF-01367338)	<1 mg/mL	84 mg/mL	<1 mg/mL
S1087	Iniparib (BSI-201)	<1 mg/mL	58 mg/mL	28 mg/mL
S2197	A-966492	<1 mg/mL	65 mg/mL	<1 mg/mL
S2178	AG14361	<1 mg/mL	12 mg/mL	<1 mg/mL
S1132	INO-1001	<1 mg/mL	27 mg/mL	27 mg/mL
S8038	UPF 1069	<1 mg/mL	56 mg/mL	<1 mg/mL
S7048	BMN 673	<1 mg/mL	96 mg/mL	96 mg/mL
S7029	AZD2461	<1 mg/mL	79 mg/mL	31 mg/mL

Product Description

Biological Activity Protocol Chemical Information Customer Reviews Product Citations Tech Support & FAQs

Biological Activity

Description	Rucaparib (AG-014699, PF-01367338) is an inhibitor of PARP with K_i of 1.4 nM.
Targets	PARP
IC50	1.4 nM (K_i) ^[1]
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. ^[1] 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. ^[2] Rucaparib inhibits PARP-1 activity by 97.1% at a concentration of 1 μM in permeabilised D283Med cells. ^[3]
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. ^[3] 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. ^[4]
Clinical Trials	Rucaparib is currently in Phase II clinical trials for locally advanced/metastatic breast or advanced ovarian cancer.
Features	Rucaparib is the phosphate salt of AG-14447 and the first PARP inhibitor to be used in clinical trials, combined with temozolomide.

Protocol(Only for Reference)

Kinase Assay: ^[1]

K_i 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. K_i is calculated by nonlinear regression analysis.
Inhibition of PARP activity	Inhibition of PARP activity in 5 × 10³ D283Med cells is measured using various concentrations of Rucaparib (0-1 μM), compared with DMSO-only. Maximally stimulated PARP activity is measured in samples of permeabilised cells by immunological detection of the amount of poly(ADP-ribose) (PAR) formed, using the 10H anti-PAR antibody, during a 6-min incubation with NAD⁺ and oligonucleotide (substrate and activator). A PAR standard curve using a GCLP-validated assay is used as reference for the assay. ^[3]

K_i 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. K_i is calculated by nonlinear regression analysis.

Inhibition of PARP activity

Inhibition of PARP activity in 5 × 10³ D283Med cells is measured using various concentrations of Rucaparib (0-1 μM), compared with DMSO-only. Maximally stimulated PARP activity is measured in samples of permeabilised cells by immunological detection of the amount of poly(ADP-ribose) (PAR) formed, using the 10H anti-PAR antibody, during a 6-min incubation with NAD⁺ and oligonucleotide (substrate and activator). A PAR standard curve using a GCLP-validated assay is used as reference for the assay. ^[3]

Cell Assay: ^[3]

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: ^[3]

Animal Models	CD-1 nude mice bearing established D283Med xenografts
Formulation	Normal saline
Dosages	1 mg/kg
Administration	One or four daily by i.p.

1

References

Chemical Information

Download Rucaparib (AG-014699 , PF-01367338) SDF

Molecular Weight (MW)	421.36
Formula	C₁₉H₁₈FN₃O.H₃PO₄
CAS No.	459868-92-9
Synonyms	AG-014447

Solubility (25°C) DMSO 84 mg/mL Water <1 mg/mL Ethanol <1 mg/mL
Storage	2 years -20°CPowder
	2 weeks4°Cin DMSO
	6 months-80°Cin DMSO

Chemical Name	8-fluoro-5-(4-((methylamino)methyl)phenyl)-3,4-dihydro-2H-azepino[5,4,3-cd]indol-1(6H)-one phosphoric acid

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Research Area

Customer Reviews (2)

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Rating

Source

J Biol Chem, 2012, 287(47), 39824-33. Rucaparib (AG-014699 , PF-01367338) purchased from Selleck

Method

Western Blotting

Cell Lines

HaCaT cells

Concentrations

1 μM

Incubation Time

30 min

Results

preincubation of purified PARP-1 with AG-014699, a potent PARP inhibitor , prior to PARP-1 activation led to decreased associa-tion between PARP-1 and XPA.

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Rating

Source

Dr David Schürmann from University of Basel. Rucaparib (AG-014699 , PF-01367338) purchased from Selleck

Method

Kruskal-Wallis and the post-hoc Dunn’s Multiple Comparison tests, immuno-staining

Cell Lines

Primary human lung fibroblast cells (MRC-5)

Concentrations

0-1 μM

Incubation Time

2 h

Results

Product Citations (3)

Embryonic lethal phenotype reveals a function of TDG in maintaining epigenetic stability. [Cortázar D, et al. Nature 2011;470(7334), 419-423]
PubMed: 21278727
Co-targeting of the PI3K pathway improves the response of BRCA1 deficient breast cancer cells to PARP1 inhibition. [Kimbung S, et al. Cancer Lett 2012;319(2), 232-241]
PubMed: 22266096
Poly(ADP-ribose) contributes to an association between poly(ADP-ribose) polymerase-1 and xeroderma pigmentosum complementation group A in nucleotide excision repair. [Schaefer NG, et al. Nucl Med Commun 2011;32(11):1046-51]
PubMed: 21956491

Tech Support & FAQs

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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Related PARP Inhibitors

ABT-888 (Veliparib)

ABT-888 (Veliparib, NSC 737664) is a potent inhibitor of PARP1 and PARP2 with K_i of 5.2 nM and 2.9 nM, respectively.
Olaparib (AZD2281)

Olaparib (AZD2281, KU0059436) is a selective inhibitor of PARP1 and PARP2 with IC50 of 5 nM and 1 nM, respectively.
Iniparib (BSI-201)

BSI-201 (Iniparib, SAR240550) is a PARP1 inhibitor.
INO-1001
INO-1001 is a potent inhibitor of PARP with IC50 of 50 nM and a mediator of oxidant-induced myocyte dysfunction during reperfusion.
AG14361
AG14361 is a potent inhibitor of PARP1 with K_i of < 5 nM.
A-966492
A-966492 is a novel and potent inhibitor of PARP1 and PARP2 with K_i of 1 nM and 1.5 nM, respectively.
MK-4827
MK-4827 is an selective inhibitor of PARP1 and PARP2 with IC50 of 3.8 nM and 2.1 nM, respectively.
PJ34
PJ-34 is a potent PARP inhibitor with EC50 of 20 nM.
AZD2461
AZD2461 is a novel PARP inhibitor with potential to bypass Pgp-mediated resistance to Olaparib.
BMN 673
BMN 673 is a novel PARP inhibitor with IC50 of 0.58 nM.

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Validation & Quality Control

Product Citations(3)

Customer Reviews(2) in vivo invitation

Quality Control & MSDS

Related Compound Libraries

Rucaparib (AG-014699 , PF-01367338) is available in the following compound libraries:

Product Information

Compare PARP Inhibitors

Research Area

Product Description

Biological Activity

Protocol(Only for Reference)

Kinase Assay: ^[1]

Cell Assay: ^[3]

Animal Study: ^[3]

References

Chemical Information

Research Area

Customer Reviews (2)

Product Citations (3)

Tech Support & FAQs

If you have any other enquiries, please leave a message.

Related PARP Inhibitors

Cell Cycle and DNA Damage Related Products

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S1060	Olaparib (AZD2281)	<1 mg/mL	87 mg/mL	<1 mg/mL
S1004	ABT-888 (Veliparib)	<1 mg/mL	17 mg/mL	<1 mg/mL
S1098	Rucaparib (AG-014699 , PF-01367338)	<1 mg/mL	84 mg/mL	<1 mg/mL
S1087	Iniparib (BSI-201)	<1 mg/mL	58 mg/mL	28 mg/mL
S2197	A-966492	<1 mg/mL	65 mg/mL	<1 mg/mL
S2178	AG14361	<1 mg/mL	12 mg/mL	<1 mg/mL
S1132	INO-1001	<1 mg/mL	27 mg/mL	27 mg/mL
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S7048	BMN 673	<1 mg/mL	96 mg/mL	96 mg/mL
S7029	AZD2461	<1 mg/mL	79 mg/mL	31 mg/mL

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Product Categories

Rucaparib (AG-014699 , PF-01367338)

Validation & Quality Control

Product Citations(3)

Customer Reviews(2) in vivo invitation

Quality Control & MSDS

Related Compound Libraries

Rucaparib (AG-014699 , PF-01367338) is available in the following compound libraries:

Product Information

Compare PARP Inhibitors

Research Area

Product Description

Biological Activity

Protocol(Only for Reference)

Kinase Assay: [1]

Cell Assay: [3]

Animal Study: [3]

References

Chemical Information

Research Area

Customer Reviews (2)

Product Citations (3)

Tech Support & FAQs

If you have any other enquiries, please leave a message.

Related PARP Inhibitors

Cell Cycle and DNA Damage Related Products

Recently Viewed Items

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Kinase Assay: ^[1]

Cell Assay: ^[3]

Animal Study: ^[3]