773059-22-6

773059-22-6 structure

Name: Rucaparib tartrate
Chemical Name: Rucaparib tartrate
CAS Number: 773059-22-6
Molecular Formula: C₂₃H₂₄FN₃O₇
Molecular Weight: 473.45
Catalog: Signaling Pathways Cell Cycle/DNA Damage PARP
Create Date: 2022-09-01 01:03:29
Modify Date: 2023-05-12 11:35:19
Rucaparib (AG014699) tartrate is an orally active, potent inhibitor of PARP proteins (PARP-1, PARP-2 and PARP-3) with a Ki of 1.4 nM for PARP1. Rucaparib tartrate is a modest hexose-6-phosphate dehydrogenase (H6PD) inhibitor. Rucaparib tartrate has the potential for castration-resistant prostate cancer (CRPC) research[1][2][3][4].

Name	Rucaparib tartrate

Description	Rucaparib (AG014699) tartrate is an orally active, potent inhibitor of PARP proteins (PARP-1, PARP-2 and PARP-3) with a Ki of 1.4 nM for PARP1. Rucaparib tartrate is a modest hexose-6-phosphate dehydrogenase (H6PD) inhibitor. Rucaparib tartrate has the potential for castration-resistant prostate cancer (CRPC) research[1][2][3][4].
Related Catalog	Research Areas >> Cancer Signaling Pathways >> Epigenetics >> PARP Signaling Pathways >> Cell Cycle/DNA Damage >> PARP
Target	PARP-1:1.4 nM (Ki) PARP-2 PARP-3
In Vitro	Rucaparib (AG014699) tartrate is a possible N-demethylation metabolite of AG14644[1]. Rucaparib (0.1, 1, 10, 100 μM; 24 hours) tartrate is cytotoxic and has the LC50 being 5 μM in Capan-1 (BRCA2 mutant) cells and only 100 nM in MX-1 (BRCA1 mutant) cells[2]. The radio-sensitization by Rucaparib tartrate is due to downstream inhibition of activation of NF-κB, and is independent of SSB repair inhibition. Rucaparib tartrate can target NF-κB activated by DNA damage and overcome toxicity observed with classical NF-κB inhibitors without compromising other vital inflammatory functions[5]. Rucaparib tartrate inhibits PARP-1 activity by 97.1% at a concentration of 1 μM in permeabilised D283Med cells[6].
In Vivo	Rucaparib (AG014699) tartrate and AG14584 significantly increase Temozolomide toxicity. Rucaparib (1 mg/kg) tartrate significantly increases Temozolomide-induced body weight loss. Rucaparib (0.1 mg/kg) tartrate esults in a 50% increase in the temozolomide-induced tumor growth delay[1]. Rucaparib (10 mg/kg for i.p. or 50, 150 mg/kg for p.o.; daily for 5 days per week for 6 weeks) tartrate significantly inhibits the growth of the tumor, and there is one complete tumor regression and two persistent partial regressions[2]. Rucaparib (150 mg/kg; p.o.; once per week for 6 weeks or three times per week for 6 weeks) tartrate has greatest antitumor effect with three complete regressions[2]. Rucaparib tartrate enhances the antitumor activity of temozolomide and indicates complete and sustained tumor regression in NB1691 and SHSY5Y xenografts[6].
References	[1]. Thomas HD, et al. Preclinical selection of a novel poly(ADP-ribose) polymerase inhibitor for clinical trial. Mol Cancer Ther, 2007, 6(3), 945-956. [2]. J Murray, et al. 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]. Matt Shirley, et al. Rucaparib: A Review in Ovarian Cancer. Target Oncol. 2019 Apr;14(2):237-246. [4]. Jianneng Li, et al. 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]. Hunter JE, et al. NF-κB mediates radio-sensitization by the PARP-1 inhibitor, AG-014699. Oncogene, 2012, 31(2), 251-264. [6]. Daniel RA, et al. Inhibition of poly(ADP-ribose) polymerase-1 enhances temozolomide and topotecan activity against childhood neuroblastoma. Clin Cancer Res, 2009, 15(4), 1241-1249.

Molecular Formula	C₂₃H₂₄FN₃O₇
Molecular Weight	473.45

773059-22-6	1424059-28-8
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