Results 11 to 20 of about 21,045 (211)

Kidney epithelium specific deletion of kelch-like ECH-associated protein 1 (Keap1) causes hydronephrosis in mice. [PDF]

BMC Nephrol, 2016
Transcription factor Nrf2 protects from experimental acute kidney injury (AKI) and is promising to limit progression in human chronic kidney disease (CKD) by upregulating multiple antioxidant genes. We recently demonstrated that deletion of Keap1, the endogenous inhibitor of Nrf2, in T lymphocytes significantly protects from AKI.
Noel S, Arend LJ, Bandapalle S, Reddy SP, Rabb H.   +4 more
europepmc   +5 more sources

Isoquinoline Kelch-like ECH-Associated Protein 1-Nuclear Factor (Erythroid-Derived 2)-like 2 (KEAP1-NRF2) Inhibitors with High Metabolic Stability. [PDF]

J Med Chem, 2020
Pharmacological activation of NRF2 (nuclear factor erythroid 2-related factor 2) arises from blocking the interaction of NRF2 with its negative regulator, KEAP1 (Kelch-like ECH-associated protein 1). We previously reported an isoquinoline-based NRF2 activator, but this compound showed negative logD7.4 and a -2 charge at physiological pH, which may have
Lazzara PR, David BP, Ankireddy A, Richardson BG, Dye K, Ratia KM, Reddy SP, Moore TW.   +7 more
europepmc   +5 more sources

Chemistry of the cysteine sensors in Kelch-like ECH-associated protein 1. [PDF]

Antioxid Redox Signal, 2010
The protein Kelch-like ECH-associated protein 1 (Keap1) is a cysteine-rich regulatory and scaffold protein. Human Keap1 contains 27 cysteines. Some of these cysteines are believed to mediate derepression of the transcription factor nuclear factor (erythroid-derived 2)-like 2 (Nrf2), which subsequently upregulates phase 2 enzymes, in response to ...
Holland R, Fishbein JC.
europepmc   +5 more sources

Kelch-like ECH-associated protein 1 (KEAP1) differentially regulates nuclear factor erythroid-2-related factors 1 and 2 (NRF1 and NRF2). [PDF]

J Biol Chem, 2018
Nuclear factor erythroid-2-related factor 1 (NRF1) and NRF2 are essential for maintaining redox homeostasis and coordinating cellular stress responses. They are highly homologous transcription factors that regulate the expression of genes bearing antioxidant-response elements (AREs).
Tian W, Rojo de la Vega M, Schmidlin CJ, Ooi A, Zhang DD.   +4 more
europepmc   +5 more sources

Deconstructing Noncovalent Kelch-like ECH-Associated Protein 1 (Keap1) Inhibitors into Fragments to Reconstruct New Potent Compounds [PDF]

Journal of Medicinal Chemistry, 2021
Targeting the protein-protein interaction (PPI) between nuclear factor erythroid 2-related factor 2 (Nrf2) and Kelch-like ECH-associated protein 1 (Keap1) is a potential therapeutic strategy to control diseases involving oxidative stress. Here, six classes of known small-molecule Keap1-Nrf2 PPI inhibitors were dissected into 77 fragments in a fragment ...
Jakob Staun Pallesen, Dilip Narayanan, Sara Marie Solbak   +2 more
exaly   +9 more sources

Replacement of a Naphthalene Scaffold in Kelch-like ECH-Associated Protein 1 (KEAP1)/Nuclear Factor (Erythroid-derived 2)-like 2 (NRF2) Inhibitors. [PDF]

J Med Chem, 2018
Activators of nuclear factor-erythroid 2-related factor 2 (NRF2) could lead to promising therapeutics for prevention and treatment of oxidative stress and inflammatory disorders. Ubiquitination and subsequent degradation of the transcription factor NRF2 is mediated by Kelch-like ECH-associated protein-1 (KEAP1). Inhibition of the KEAP1/NRF2 interaction
Richardson BG, Jain AD, Potteti HR, Lazzara PR, David BP, Tamatam CR, Choma E, Skowron K, Dye K, Siddiqui Z, Wang YT, Krunic A, Reddy SP, Moore TW.   +13 more
europepmc   +5 more sources

Therapeutic targeting of the NRF2 and KEAP1 partnership in chronic diseases [PDF]

Nature Reviews Drug Discovery, 2019
The transcription factor NF-E2 p45-related factor 2 (NRF2; encoded by NFE2L2) and its principal negative regulator, the E3 ligase adaptor Kelch-like ECH-associated protein 1 (KEAP1), are critical in the maintenance of redox, metabolic and protein ...
Attucks, Otis C., Cousin, Sharon P., Cuadrado, Antonio, Dinkova-Kostova, Albena, Franklin, Stephen, Hayes, John, Kensler, Thomas W., Levonen, Anna-Liisa, Rojo, Ana I., Rumsey, William L., Wells, Geoffrey   +10 more
core   +4 more sources

NRF2 Cysteine Residues Are Critical for Oxidant/Electrophile-Sensing, Kelch-Like ECH-Associated Protein-1-Dependent Ubiquitination-Proteasomal Degradation, and Transcription Activation [PDF]

Molecular Pharmacology, 2009
Cells respond to oxidants and electrophiles by activating receptor/transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) to coordinate the induction of cytoprotective genes critical for defense against oxidative and other stresses. Activation involves blocking the ubiquitination-proteasomal degradation of Nrf2.
Qiang
exaly   +3 more sources

Loss of Kelch-Like ECH-Associated Protein 1 Function in Prostate Cancer Cells Causes Chemoresistance and Radioresistance and Promotes Tumor Growth [PDF]

Molecular Cancer Therapeutics, 2010
Abstract Loss-of-function mutations in the nuclear factor erythroid-2–related factor 2 (Nrf2) inhibitor Kelch-like ECH-associated protein 1 (Keap1) result in increased Nrf2 activity in non–small cell lung cancer and confer therapeutic resistance.
Anju Singh, Ponvijay Kombairaju, Manish Bodas   +2 more
exaly   +3 more sources

Identification and Characterization of MCM3 as a Kelch-like ECH-associated Protein 1 (KEAP1) Substrate. [PDF]

J Biol Chem, 2016
KEAP1 is a substrate adaptor protein for a CUL3-based E3 ubiquitin ligase. Ubiquitylation and degradation of the antioxidant transcription factor NRF2 is considered the primary function of KEAP1; however, few other KEAP1 substrates have been identified.
Mulvaney KM, Matson JP, Siesser PF, Tamir TY, Goldfarb D, Jacobs TM, Cloer EW, Harrison JS, Vaziri C, Cook JG, Major MB.   +10 more
europepmc   +4 more sources