Advances in developing noncovalent small molecules targeting Keap1

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

Standard

Advances in developing noncovalent small molecules targeting Keap1. / Barreca, Marilia; Qin, Yuting; Hélène Cadot, Marie Elodie; Barraja, Paola; Bach, Anders.

In: Drug Discovery Today, Vol. 28, No. 12, 103800, 2023.

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

Harvard

Barreca, M, Qin, Y, Hélène Cadot, ME, Barraja, P & Bach, A 2023, 'Advances in developing noncovalent small molecules targeting Keap1', Drug Discovery Today, vol. 28, no. 12, 103800. https://doi.org/10.1016/j.drudis.2023.103800

APA

Barreca, M., Qin, Y., Hélène Cadot, M. E., Barraja, P., & Bach, A. (2023). Advances in developing noncovalent small molecules targeting Keap1. Drug Discovery Today, 28(12), [103800]. https://doi.org/10.1016/j.drudis.2023.103800

Vancouver

Barreca M, Qin Y, Hélène Cadot ME, Barraja P, Bach A. Advances in developing noncovalent small molecules targeting Keap1. Drug Discovery Today. 2023;28(12). 103800. https://doi.org/10.1016/j.drudis.2023.103800

Author

Barreca, Marilia ; Qin, Yuting ; Hélène Cadot, Marie Elodie ; Barraja, Paola ; Bach, Anders. / Advances in developing noncovalent small molecules targeting Keap1. In: Drug Discovery Today. 2023 ; Vol. 28, No. 12.

Bibtex

@article{27e1d7bc601549918ba8ac7baf87c364,

title = "Advances in developing noncovalent small molecules targeting Keap1",

abstract = "Kelch-like ECH-associated protein 1 (Keap1) is a drug target for diseases involving oxidative stress and inflammation. There are three covalent Keap1-binding drugs on the market, but noncovalent compounds that inhibit the interaction between Keap1 and nuclear factor erythroid 2-related factor 2 (Nrf2) represent an attractive alternative. Both compound types prevent degradation of Nrf2, leading to the expression of antioxidant and antiinflammatory proteins. However, their off-target profiles differ as do their exact pharmacodynamic effects. Here, we discuss the opportunities and challenges of targeting Keap1 with covalent versus noncovalent inhibitors. We then provide a comprehensive overview of current noncovalent Keap1-Nrf2 inhibitors, with a focus their on pharmacological effects, to examine the therapeutic potential for this compound class.",

author = "Marilia Barreca and Yuting Qin and {H{\'e}l{\`e}ne Cadot}, {Marie Elodie} and Paola Barraja and Anders Bach",

year = "2023",

doi = "10.1016/j.drudis.2023.103800",

language = "English",

volume = "28",

journal = "Drug Discovery Today: BIOSILICO",

issn = "1359-6446",

publisher = "Elsevier Ltd. * Trends Journals",

number = "12",

}

RIS

TY - JOUR

T1 - Advances in developing noncovalent small molecules targeting Keap1

AU - Barreca, Marilia

AU - Qin, Yuting

AU - Hélène Cadot, Marie Elodie

AU - Barraja, Paola

AU - Bach, Anders

PY - 2023

Y1 - 2023

N2 - Kelch-like ECH-associated protein 1 (Keap1) is a drug target for diseases involving oxidative stress and inflammation. There are three covalent Keap1-binding drugs on the market, but noncovalent compounds that inhibit the interaction between Keap1 and nuclear factor erythroid 2-related factor 2 (Nrf2) represent an attractive alternative. Both compound types prevent degradation of Nrf2, leading to the expression of antioxidant and antiinflammatory proteins. However, their off-target profiles differ as do their exact pharmacodynamic effects. Here, we discuss the opportunities and challenges of targeting Keap1 with covalent versus noncovalent inhibitors. We then provide a comprehensive overview of current noncovalent Keap1-Nrf2 inhibitors, with a focus their on pharmacological effects, to examine the therapeutic potential for this compound class.

AB - Kelch-like ECH-associated protein 1 (Keap1) is a drug target for diseases involving oxidative stress and inflammation. There are three covalent Keap1-binding drugs on the market, but noncovalent compounds that inhibit the interaction between Keap1 and nuclear factor erythroid 2-related factor 2 (Nrf2) represent an attractive alternative. Both compound types prevent degradation of Nrf2, leading to the expression of antioxidant and antiinflammatory proteins. However, their off-target profiles differ as do their exact pharmacodynamic effects. Here, we discuss the opportunities and challenges of targeting Keap1 with covalent versus noncovalent inhibitors. We then provide a comprehensive overview of current noncovalent Keap1-Nrf2 inhibitors, with a focus their on pharmacological effects, to examine the therapeutic potential for this compound class.

U2 - 10.1016/j.drudis.2023.103800

DO - 10.1016/j.drudis.2023.103800

M3 - Review

C2 - 37852355

VL - 28

JO - Drug Discovery Today: BIOSILICO

JF - Drug Discovery Today: BIOSILICO

SN - 1359-6446

IS - 12

M1 - 103800

ER -

ID: 370663219