Christina R. Majer

The PARP14 inhibitor RBN-3143 suppresses lung inflammation in preclinical models

Mario Niepel, Melissa M. Vasbinder, Jennifer R. Molina, Bin Gui et autres

PARP14 is an enzyme of the ADP-ribosyltransferase (ART) family which modifies its substrates by ADP-ribosylation. Published work suggests that PARP14 promotes Th2/Th17 signaling in immune cells by amplifying STAT6- and STAT3-driven transcription, thereby modulating inflammation. PARP14 expression is promoted by interferons and …

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Abstract 2154: PARP7 inhibitor RBN-2397 increases tumoral IFN signaling leading to various tumor cell intrinsic effects and tumor regressions in mouse models

Jennifer R. Molina, Joseph M. Gozgit, Melissa M. Vasbinder, Ryan Abo et autres

Abstract Targeting cytosolic nucleic acid sensing pathways to activate the Type I interferon (IFN) response is an emerging therapeutic strategy being explored in oncology. The PARP family consists of seventeen enzymes that regulate fundamental biological processes including response to cellular stress. PARP7 …

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PARP7 negatively regulates the type I interferon response in cancer cells and its inhibition triggers antitumor immunity

Joseph M. Gozgit, Melissa M. Vasbinder, Ryan Abo, Kaiko Kunii et autres

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Abstract 48: RBN-2397: A potent and selective small molecule inhibitor of PARP7 that induces tumor-derived antitumor immunity dependent on CD8 T cells

Joseph M. Gozgit, Melissa M. Vasbinder, Ryan Abo, Kaiko Kunii et autres

Abstract Targeting cytosolic nucleic acid sensing pathways and the Type I interferon (IFN) response is an emerging therapeutic strategy being explored in oncology. The PARP family consists of seventeen enzymes that regulate fundamental biological processes including response to cellular stress. In contrast …

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Abstract 1348: Targeted degradation of PARP14 Using a heterobifunctional small molecule

Tim J. Wigle, Yue Ren, Jennifer R. Molina, Danielle J. Blackwell et autres

Abstract PARP14 is an interferon-stimulated gene that is overexpressed in multiple tumor types and has been shown to promote the pro-tumor M2 polarization of macrophages and support Th2/Th17 signaling in models of allergic airway disease. PARP14 is a large 203 kDa protein …

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Abstract 1344: Small molecule inhibitor of CD38 modulates its intra- and extracellular functions leading to antitumor activity

Prashant B. Shambharkar, Danielle J. Blackwell, Melissa M. Vasbinder, Laurie B. Schenkel et autres

Abstract CD38 is an ADP-ribosyl cyclase that converts NAD+ to ADP-ribose (ADPR) or cyclic ADPR (cADPR) and nicotinamide. The enzyme can exist in either an ecto- or endo-catalytic orientation with different sub-cellular localization, and therefore can regulate internal and external NAD+ pools. …

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Targeted Degradation of PARP14 Using a Heterobifunctional Small Molecule

Tim J. Wigle, Yue Ren, Jennifer R. Molina, Danielle J. Blackwell et autres

Abstract PARP14 is an interferon‐stimulated gene that is overexpressed in multiple tumor types, influencing pro‐tumor macrophage polarization as well as suppressing the antitumor inflammation response by modulating IFN‐γ and IL‐4 signaling. PARP14 is a 203 kDa protein that possesses a catalytic domain …

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A potent and selective PARP14 inhibitor decreases protumor macrophage gene expression and elicits inflammatory responses in tumor explants

Laurie B. Schenkel, Jennifer R. Molina, Kerren K. Swinger, Ryan Abo et autres

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Abstract DDT02-01: RBN-2397: A first-in-class PARP7 inhibitor targeting a newly discovered cancer vulnerability in stress-signaling pathways

Melissa M. Vasbinder, Joseph M. Gozgit, Ryan Abo, Kaiko Kunii et autres

Abstract RBN-2397: A first-in-class PARP7 inhibitor targeting a newly discovered cancer vulnerability in stress-signaling pathways PARP7 is a monoPARP that catalyzes the transfer of single units of ADP-ribose onto substrates to change their function (MARylation). PARP7 expression is increased by cellular stresses, …

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Abstract 3405: PARP7 negatively regulates the type I interferon response in cancer cells and its inhibition leads to tumor regression

Joseph M. Gozgit, Melissa M. Vasbinder, Ryan Abo, Kaiko Kunii et autres

Abstract Targeting cytosolic nucleic acid sensing pathways and the Type I interferon (IFN) response is an emerging therapeutic strategy being explored in oncology. PARP7 is a member of the monoPARP class of enzymes, which catalyze the transfer of single units of ADP-ribose …

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Abstract 506: A bespoke screening platform to study mono(ADP-ribosylation)

Tim J. Wigle, Danielle J. Blackwell, Laurie B. Schenkel, Yue Ren et autres

Abstract Mono(ADP-ribosylation) (MARylation) and poly(ADP-ribosylation) (PARylation) are post-translational modifications deposited on multiple amino acids by PARP enzymes using nicotinamide adenine dinucleotide (NAD+) as the ADP-ribose donating substrate. While there are approved drugs and clinical trials on-going for inhibitors of the polyPARP enzymes …

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In Vitro and Cellular Probes to Study PARP Enzyme Target Engagement

Tim J. Wigle, Danielle J. Blackwell, Laurie B. Schenkel, Yue Ren et autres

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