Sara Fournier

Supplementary Data from RP-3500: A Novel, Potent, and Selective ATR Inhibitor that is Effective in Preclinical Models as a Monotherapy and in Combination with PARP Inhibitors

Anne Roulston, Michal Zimmermann, Robert Papp, Alexander M. Skeldon et autres

Supplementary Methods, Tables, Figures and References

The Discovery of RP-2119: A Potent, Selective, and Orally Bioavailable Polθ ATPase Inhibitor

Philippe Mochirian, Robert Papp, Marie‐Claude Mathieu, Gino B. Ferraro et autres

Abstract DNA polymerase theta (Polθ) plays a critical role in repairing DNA double-strand breaks through microhomology-mediated end joining (MMEJ) and has emerged as a key synthetic lethal drug target in cancers with homologous recombination (HR) deficiencies. Its inhibition has shown a strong …

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Single pulmonary nanopolystyrene exposure in late-stage pregnancy dysregulates maternal and fetal cardiovascular function

Chelsea M. Cary, Sara Fournier, Sarah E. Adams, Xiaoming Wang et autres

Large-scale production and waste of plastic materials have resulted in widespread environmental contamination by the breakdown product of bulk plastic materials to micro- and nanoplastics (MNPs). The small size of these particles enables their suspension in the air, making pulmonary exposure inevitable. …

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Discovery of the Potent and Selective ATR Inhibitor Camonsertib (RP-3500)

W. Cameron Black, Abbas Abdoli, Xiuli An, Anick Auger et autres

ATR is a key kinase in the DNA-damage response (DDR) that is synthetic lethal with several other DDR proteins, making it an attractive target for the treatment of genetically selected solid tumors. Herein we describe the discovery of a novel ATR inhibitor …

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Data from RP-3500: A Novel, Potent, and Selective ATR Inhibitor that is Effective in Preclinical Models as a Monotherapy and in Combination with PARP Inhibitors

Anne Roulston, Michal Zimmermann, Robert Papp, Alexander M. Skeldon et autres

Abstract Ataxia telangiectasia and Rad3-related (ATR) kinase protects genome integrity during DNA replication. RP-3500 is a novel, orally bioavailable clinical-stage ATR kinase inhibitor (NCT04497116). RP-3500 is highly potent with IC50 values of 1.0 and 0.33 nmol/L in biochemical and cell-based assays, respectively. …

Data from RP-3500: A Novel, Potent, and Selective ATR Inhibitor that is Effective in Preclinical Models as a Monotherapy and in Combination with PARP Inhibitors

Anne Roulston, Michal Zimmermann, Robert Papp, Alexander M. Skeldon et autres

Abstract Ataxia telangiectasia and Rad3-related (ATR) kinase protects genome integrity during DNA replication. RP-3500 is a novel, orally bioavailable clinical-stage ATR kinase inhibitor (NCT04497116). RP-3500 is highly potent with IC50 values of 1.0 and 0.33 nmol/L in biochemical and cell-based assays, respectively. …

Supplementary Data from RP-3500: A Novel, Potent, and Selective ATR Inhibitor that is Effective in Preclinical Models as a Monotherapy and in Combination with PARP Inhibitors

Anne Roulston, Michal Zimmermann, Robert Papp, Alexander M. Skeldon et autres

Supplementary Methods, Tables, Figures and References

Supplementary Data from RP-3500: A Novel, Potent, and Selective ATR Inhibitor that is Effective in Preclinical Models as a Monotherapy and in Combination with PARP Inhibitors

Anne Roulston, Michal Zimmermann, Robert Papp, Alexander M. Skeldon et autres

Supplementary Methods, Tables, Figures and References

ATR Inhibitor Camonsertib (RP-3500) Suppresses Early Stage Erythroblasts By Mediating Ferroptosis

Maayan Levy, Gino B. Ferraro, Li Li, Yongshuai Han et autres

Background: Ataxia telangiectasia mutated and Rad3-related kinase (ATR) mediates cellular response to replication stress and DNA damage. Camonsertib is a potent and selective ATR inhibitor (ATRi) with strong pre-clinical efficacy and promising clinical activity (NCT04497116) in patients with advanced solid tumors with …

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The PKMYT1 inhibitor RP-6306 has synergistic efficacy with carboplatin in CCNE1 amplified tumor models

Jimmy Fourtounis, D. Gallo, Anne Roulston, Rita de Cássia Stocco et autres

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Guiding ATR and PARP inhibitor combinations with chemogenomic screens

Michal Zimmermann, Cynthia Bernier, Beatrice Kaiser, Sara Fournier et autres

Combinations of ataxia telangiectasia- and Rad3-related kinase inhibitors (ATRis) and poly(ADP-ribose) polymerase inhibitors (PARPis) synergistically kill tumor cells through modulation of complementary DNA repair pathways, but their tolerability is limited by hematological toxicities. To address this, we performed a genome-wide CRISPR-Cas9 screen …

CCNE1 amplification is synthetic lethal with PKMYT1 kinase inhibition

David Gallo, Jordan T.F. Young, Jimmy Fourtounis, Giovanni Martino et autres

Abstract Amplification of the CCNE1 locus on chromosome 19q12 is prevalent in multiple tumour types, particularly in high-grade serous ovarian cancer, uterine tumours and gastro-oesophageal cancers, where high cyclin E levels are associated with genome instability, whole-genome doubling and resistance to cytotoxic …

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