Heterocyclic chalcone activators of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) with improved in vivo efficacy

Nicole Lounsbury; George Mateo; Brielle Jones; Srinivas Papaiahgari; Rajash K. Thimmulappa; Christiana Teijaro; John Gordon; Kenneth Korzekwa; Min Ye; Graham Allaway; Magid Abou-Gharbia; Shyam Biswal; Wayne Childers

doi:10.1016/j.bmc.2015.07.056

Heterocyclic chalcone activators of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) with improved in vivo efficacy

Nicole Lounsbury, George Mateo, Brielle Jones, Srinivas Papaiahgari, Rajash K. Thimmulappa, Christiana Teijaro, John Gordon, Kenneth Korzekwa, Min Ye, Graham Allaway, Magid Abou-Gharbia, Shyam Biswal, Wayne Childers

Bloomberg School of Public Health

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

11 Scopus citations

Abstract

Nrf2 activators represent a good drug target for designing agents to treat diseases associated with oxidative stress. Building upon previous work, we designed and prepared a series of heterocyclic chalcone-based Nrf2 activators with reduced lipophilicity and, in some cases, greater in vitro potency compared to the respective carbocyclic scaffold. These changes resulted in enhanced oral bioavailability and a superior pharmacodynamic effect in vivo.

Original language	English (US)
Pages (from-to)	5352-5359
Number of pages	8
Journal	Bioorganic and Medicinal Chemistry
Volume	23
Issue number	17
DOIs	https://doi.org/10.1016/j.bmc.2015.07.056
State	Published - Sep 1 2015

Keywords

Bioavailability
Chalcone
Keap1
Nrf2
Solubility

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

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10.1016/j.bmc.2015.07.056

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Lounsbury, N., Mateo, G., Jones, B., Papaiahgari, S., Thimmulappa, R. K., Teijaro, C., Gordon, J., Korzekwa, K., Ye, M., Allaway, G., Abou-Gharbia, M., Biswal, S., & Childers, W. (2015). Heterocyclic chalcone activators of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) with improved in vivo efficacy. Bioorganic and Medicinal Chemistry, 23(17), 5352-5359. https://doi.org/10.1016/j.bmc.2015.07.056

Lounsbury, N, Mateo, G, Jones, B, Papaiahgari, S, Thimmulappa, RK, Teijaro, C, Gordon, J, Korzekwa, K, Ye, M, Allaway, G, Abou-Gharbia, M, Biswal, S & Childers, W 2015, 'Heterocyclic chalcone activators of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) with improved in vivo efficacy', Bioorganic and Medicinal Chemistry, vol. 23, no. 17, pp. 5352-5359. https://doi.org/10.1016/j.bmc.2015.07.056

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AU - Papaiahgari, Srinivas

AU - Thimmulappa, Rajash K.

AU - Teijaro, Christiana

AU - Gordon, John

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AU - Ye, Min

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AU - Abou-Gharbia, Magid

AU - Biswal, Shyam

AU - Childers, Wayne

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Heterocyclic chalcone activators of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) with improved in vivo efficacy

Abstract

Keywords

ASJC Scopus subject areas

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