Orally Bioavailable Quinoxaline Inhibitors of 15-Prostaglandin Dehydrogenase (15-PGDH) Promote Tissue Repair and Regeneration

Bin Hu; Kosuke Toda; Xiaoyu Wang; Monika I. Antczak; Julianne Smith; Sophie Geboers; Gen Nishikawa; Hongyun Li; Dawn Dawson; Stephen Fink; Amar B. Desai; Noelle S. Williams; Sanford D. Markowitz; Joseph M. Ready

doi:10.1021/acs.jmedchem.2c01299

Orally Bioavailable Quinoxaline Inhibitors of 15-Prostaglandin Dehydrogenase (15-PGDH) Promote Tissue Repair and Regeneration

Bin Hu, Kosuke Toda, Xiaoyu Wang, Monika I. Antczak, Julianne Smith, Sophie Geboers, Gen Nishikawa, Hongyun Li, Dawn Dawson, Stephen Fink, Amar B. Desai, Noelle S. Williams, Sanford D. Markowitz, Joseph M. Ready

Research output: Contribution to journal › Article › peer-review

2 Scopus citations

Abstract

15-Prostaglandin dehydrogenase (15-PGDH) regulates the concentration of prostaglandin E2 in vivo. Inhibitors of 15-PGDH elevate PGE2 levels and promote tissue repair and regeneration. Here, we describe a novel class of quinoxaline amides that show potent inhibition of 15-PGDH, good oral bioavailability, and protective activity in mouse models of ulcerative colitis and recovery from bone marrow transplantation.

Original language	English (US)
Pages (from-to)	15327-15343
Number of pages	17
Journal	Journal of Medicinal Chemistry
Volume	65
Issue number	22
DOIs	https://doi.org/10.1021/acs.jmedchem.2c01299
State	Published - Nov 24 2022

ASJC Scopus subject areas

Molecular Medicine
Drug Discovery

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Hu, B., Toda, K., Wang, X., Antczak, M. I., Smith, J., Geboers, S., Nishikawa, G., Li, H., Dawson, D., Fink, S., Desai, A. B., Williams, N. S., Markowitz, S. D., & Ready, J. M. (2022). Orally Bioavailable Quinoxaline Inhibitors of 15-Prostaglandin Dehydrogenase (15-PGDH) Promote Tissue Repair and Regeneration. Journal of Medicinal Chemistry, 65(22), 15327-15343. https://doi.org/10.1021/acs.jmedchem.2c01299

Hu, B, Toda, K, Wang, X, Antczak, MI, Smith, J, Geboers, S, Nishikawa, G, Li, H, Dawson, D, Fink, S, Desai, AB, Williams, NS, Markowitz, SD & Ready, JM 2022, 'Orally Bioavailable Quinoxaline Inhibitors of 15-Prostaglandin Dehydrogenase (15-PGDH) Promote Tissue Repair and Regeneration', Journal of Medicinal Chemistry, vol. 65, no. 22, pp. 15327-15343. https://doi.org/10.1021/acs.jmedchem.2c01299

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abstract = "15-Prostaglandin dehydrogenase (15-PGDH) regulates the concentration of prostaglandin E2 in vivo. Inhibitors of 15-PGDH elevate PGE2 levels and promote tissue repair and regeneration. Here, we describe a novel class of quinoxaline amides that show potent inhibition of 15-PGDH, good oral bioavailability, and protective activity in mouse models of ulcerative colitis and recovery from bone marrow transplantation.",

author = "Bin Hu and Kosuke Toda and Xiaoyu Wang and Antczak, {Monika I.} and Julianne Smith and Sophie Geboers and Gen Nishikawa and Hongyun Li and Dawn Dawson and Stephen Fink and Desai, {Amar B.} and Williams, {Noelle S.} and Markowitz, {Sanford D.} and Ready, {Joseph M.}",

year = "2022",

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doi = "10.1021/acs.jmedchem.2c01299",

language = "English (US)",

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AU - Hu, Bin

AU - Toda, Kosuke

AU - Wang, Xiaoyu

AU - Antczak, Monika I.

AU - Smith, Julianne

AU - Geboers, Sophie

AU - Nishikawa, Gen

AU - Li, Hongyun

AU - Dawson, Dawn

AU - Fink, Stephen

AU - Desai, Amar B.

AU - Williams, Noelle S.

AU - Markowitz, Sanford D.

AU - Ready, Joseph M.

PY - 2022/11/24

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AB - 15-Prostaglandin dehydrogenase (15-PGDH) regulates the concentration of prostaglandin E2 in vivo. Inhibitors of 15-PGDH elevate PGE2 levels and promote tissue repair and regeneration. Here, we describe a novel class of quinoxaline amides that show potent inhibition of 15-PGDH, good oral bioavailability, and protective activity in mouse models of ulcerative colitis and recovery from bone marrow transplantation.

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Orally Bioavailable Quinoxaline Inhibitors of 15-Prostaglandin Dehydrogenase (15-PGDH) Promote Tissue Repair and Regeneration

Abstract

ASJC Scopus subject areas

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