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1. Supplementary Table S3 from Novel, Selective Inhibitors of USP7 Uncover Multiple Mechanisms of Antitumor Activity In Vitro and In Vivo

Author

Paul D. Kassner, Dirk G. Brockstedt, David Wustrow, Jacob Schwarz, Christophe Colas, Jack Maung, Akinori Okano, Xinping Han, Nathan Kozon, Delia Bradford, Lisa A. Marshall, Silpa Suthram, Kyle Young, Betty Abraham, Deepa Pookot, Niket Shah, Jerick Sanchez, Steve T. Wong, Scott Jacobson, Cynthia Cho, Payal Rana, Berenger Biannic, Dennis X. Hu, Paul R. Leger, Gene Cutler, Michael T. Sun, and Yamini M. Ohol

Abstract

Gene sets significantly upregulated upon USP7 inhibitor treatment of H526 cells.

Published
2023
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2. Supplementary Table S4 from Novel, Selective Inhibitors of USP7 Uncover Multiple Mechanisms of Antitumor Activity In Vitro and In Vivo

Author

Paul D. Kassner, Dirk G. Brockstedt, David Wustrow, Jacob Schwarz, Christophe Colas, Jack Maung, Akinori Okano, Xinping Han, Nathan Kozon, Delia Bradford, Lisa A. Marshall, Silpa Suthram, Kyle Young, Betty Abraham, Deepa Pookot, Niket Shah, Jerick Sanchez, Steve T. Wong, Scott Jacobson, Cynthia Cho, Payal Rana, Berenger Biannic, Dennis X. Hu, Paul R. Leger, Gene Cutler, Michael T. Sun, and Yamini M. Ohol

Abstract

Genes whose expression is significantly altered upon USP7 inhibitor treatment of H526 cells.

Published
2023
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3. Data from Novel, Selective Inhibitors of USP7 Uncover Multiple Mechanisms of Antitumor Activity In Vitro and In Vivo

Author

Paul D. Kassner, Dirk G. Brockstedt, David Wustrow, Jacob Schwarz, Christophe Colas, Jack Maung, Akinori Okano, Xinping Han, Nathan Kozon, Delia Bradford, Lisa A. Marshall, Silpa Suthram, Kyle Young, Betty Abraham, Deepa Pookot, Niket Shah, Jerick Sanchez, Steve T. Wong, Scott Jacobson, Cynthia Cho, Payal Rana, Berenger Biannic, Dennis X. Hu, Paul R. Leger, Gene Cutler, Michael T. Sun, and Yamini M. Ohol

Abstract

The deubiquitinase USP7 regulates the levels of multiple proteins with roles in cancer progression and immune response. Thus, USP7 inhibition may decrease oncogene function, increase tumor suppressor function, and sensitize tumors to DNA-damaging agents. We have discovered a novel chemical series that potently and selectively inhibits USP7 in biochemical and cellular assays. Our inhibitors reduce the viability of multiple TP53 wild-type cell lines, including several hematologic cancer and MYCN-amplified neuroblastoma cell lines, as well as a subset of TP53-mutant cell lines in vitro. Our work suggests that USP7 inhibitors upregulate transcription of genes normally silenced by the epigenetic repressor complex, polycomb repressive complex 2 (PRC2), and potentiate the activity of PIM and PI3K inhibitors as well as DNA-damaging agents. Furthermore, oral administration of USP7 inhibitors inhibits MM.1S (multiple myeloma; TP53 wild type) and H526 (small cell lung cancer; TP53 mutant) tumor growth in vivo. Our work confirms that USP7 is a promising, pharmacologically tractable target for the treatment of cancer.

Published
2023
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4. Supplementary Data from Novel, Selective Inhibitors of USP7 Uncover Multiple Mechanisms of Antitumor Activity In Vitro and In Vivo

Author

Paul D. Kassner, Dirk G. Brockstedt, David Wustrow, Jacob Schwarz, Christophe Colas, Jack Maung, Akinori Okano, Xinping Han, Nathan Kozon, Delia Bradford, Lisa A. Marshall, Silpa Suthram, Kyle Young, Betty Abraham, Deepa Pookot, Niket Shah, Jerick Sanchez, Steve T. Wong, Scott Jacobson, Cynthia Cho, Payal Rana, Berenger Biannic, Dennis X. Hu, Paul R. Leger, Gene Cutler, Michael T. Sun, and Yamini M. Ohol

Abstract

Supplementary Figures S1-S6 and legends, and Tables S1, S2, S5, S6, S7.

Published
2023
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5. Novel, Selective Inhibitors of USP7 Uncover Multiple Mechanisms of Antitumor Activity

Author

Yamini M, Ohol, Michael T, Sun, Gene, Cutler, Paul R, Leger, Dennis X, Hu, Berenger, Biannic, Payal, Rana, Cynthia, Cho, Scott, Jacobson, Steve T, Wong, Jerick, Sanchez, Niket, Shah, Deepa, Pookot, Betty, Abraham, Kyle, Young, Silpa, Suthram, Lisa A, Marshall, Delia, Bradford, Nathan, Kozon, Xinping, Han, Akinori, Okano, Jack, Maung, Christophe, Colas, Jacob, Schwarz, David, Wustrow, Dirk G, Brockstedt, and Paul D, Kassner

Subjects
Models, Molecular, Ubiquitin-Specific Peptidase 7, Mice, Cell Line, Tumor, Cell Culture Techniques, Animals, Humans, Female
Abstract

The deubiquitinase USP7 regulates the levels of multiple proteins with roles in cancer progression and immune response. Thus, USP7 inhibition may decrease oncogene function, increase tumor suppressor function, and sensitize tumors to DNA-damaging agents. We have discovered a novel chemical series that potently and selectively inhibits USP7 in biochemical and cellular assays. Our inhibitors reduce the viability of multiple

Published
2020

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