keap

VVD-130037 is a small molecule activator specifically targeting Kelch-like ECH-associated protein 1 (KEAP1) with potential antitumor activity.VVD-130037 inhibits tumor growth in advanced solid tumors by degrading NRF2.

Keap1-IN-1 (Compound 27) is an inhibitor of Keap1, functioning by covalently modifying the Cys151 residue on the BTB domain of KEAP1, thereby disrupting the interaction between Keap and Nrf. It enhances the mRNA expression of the antioxidant response element (ARE) dependent gene NQO1, with an EC50 of 160 nM, and exhibits cytotoxicity in U2OS cells, with an EC50 of 527 nM.

Keap1-Nrf2-IN-3 is a KEAP1:NRF2 protein-protein interaction inhibitor with a Kd value of 2.5 nM for the KEAP1 protein.

Keap1-Nrf2-IN-22 (compound 19) acts as a Keap1-Nrf2 inhibitor with a KD2 value of 42.2 nM. It is utilized in research focused on acute lung injury (ALI) and cerebral ischemia reperfusion (I R) injuries.

Keap1-Nrf2-IN-24 (compound 57) is an effective Keap1-Nrf2 inhibitor with a Ki value of 13 nM. This compound enhances the protein expression of TRXR1 and NQO1, as well as the mRNA expression of AKR1B10. Additionally, Keap1-Nrf2-IN-24 demonstrates good metabolic stability.

Keap1-Nrf2-IN-23 (compound 56) acts as an inhibitor of the Keap1–Nrf2 PPI (IC50=16.0 nM). It exhibits a Kd value of 3.07 nM when binding to Keap1 and demonstrates oral activity.

KEAP1-NRF2PPI-IN-1 (compound 23) is an inhibitor targeting the KEAP1-NRF2 interaction. In DNA damage tests, its IC50 values are 136 nM in human TK6 cell lines and 62 nM in insect SF9 cell lines.

Keap1-Nrf2-IN-25 (Compound 19) is a potent Keap1-Nrf2 inhibitor with an IC50 of 0.55 μM and exhibits a Keap1 binding affinity (Kd of 0.50 μM). This compound activates Nrf2, reducing reactive oxygen species (ROS) and pro-inflammatory cytokines (IL-1β, IL-6). Additionally, Keap1-Nrf2-IN-25 provides protective effects against DSS-induced colitis.

Keap1-Nrf2-IN-4, a powerful neddylation inhibitor, demonstrates significant anti-proliferation activity against MGC-803 cells (IC50 = 2.55 μM), effectively impeding their migration and inducing apoptosis. Additionally, it effectively inhibits tumor growth while exhibiting minimal toxicity [1].

Keap1-Nrf2-IN-5 is a potent inhibitor of Keap1-Nrf2 PPI (Keap1-Nrf2 protein-protein interaction) (IC50: 4.1 μM, Kd: 3.7 μM).

Keap1-Nrf2-IN-14 is a KEAP1-NRF2 inhibitor that effectively disrupts the KEAP1-NRF2 interaction (IC50: 75 nM) with a Kd=24 nM for KEAP1. Keap1-Nrf2-IN-14 induces the expression of NRF2 target genes and is able to enhance downstream antioxidant and anti-inflammatory effects. -Nrf2-IN-14 can be used to study oxidative stress-related inflammation.

eap1-Nrf2-IN-12 is a potent inhibitor of Keap1-Nrf2 (IC50: 2.30 μM). eap1-Nrf2-IN-12 is metabolically stable in human liver microsomes.

Keap1-Nrf2-IN-1 TFA (compound35) is a Keap1-Nrf2 protein-protein interaction inhibitor (IC50: 43 nM) that activates Nrf2-regulated cytoprotective responses and antagonizes acetaminophen-induced liver injury in both cellular and in vivo models.

Keap1-Nrf2-IN-11 (Compound 6k), a potent Keap1-Nrf2 inhibitor, exhibits a dissociation constant (KD) of 0.21 nM. It hampers the production of reactive oxygen species (ROS) and nitric oxide (NO), as well as the expression of tumor necrosis factor-alpha (TNF-α). By promoting Nrf2 nuclear translocation, it mitigates inflammation and is utilized in anti-inflammatory studies [1].

Keap1-Nrf2-IN-13 is a potent inhibitor of the Keap1-Nrf2 protein-protein interaction (PPI) with an IC50 value of 0.15 μM, indicating high efficacy. It binds strongly to Keap1 by forming hydrogen bonds with critical polar residues (Asn414, Arg415, Arg483, Gln530), showcasing specificity. This compound has implications for research into diseases associated with oxidative stress and inflammation, such as pulmonary fibrosis, chronic obstructive pulmonary disease (COPD), and cancers, due to its mechanism of action.

Keap1-Nrf2-IN-6 is a potent, selective inhibitor of the Keap1-Nrf2 protein−protein interaction (PPI), demonstrating an inhibitory concentration (IC50) of 41 nM and a dissociation constant (Kd) of 68 nM.

Keap1-Nrf2-IN-9 (compound 11) is a potent inhibitor of the Keap1-Nrf2 protein-protein interaction (PPI) with an IC50 value of 0.575 µM, enhancing the expression of Nrf2 target genes such as heme oxygenase 1 (Hmox1), glutathione S-transferase P (GstP), and glutamate-cysteine ligase catalytic (Gclc) and modulatory (Gclm) subunits, while not being cytotoxic to ARPE19 cells [1].

Keap1-Nrf2-IN-15 (Compound 24a) is a potent inhibitor of the Keap1-Nrf2 protein-protein interaction, with IC50 values of 77 nM in a fluorescence polarization (FP) assay and 2.5 nM in a time-resolved fluorescence resonance energy transfer (TR-FRET) assay [1].

Keap1-Nrf2-IN-16 is a biologically active peptide with KEAP1 binding activity.

Keap1-Nrf2-IN-10 (compound 15) is a potent inducer of NQO1 that effectively mitigates oxidative stress in gamma-irradiated mice by reducing MDA and ROS levels, and NQO1 in the liver, thereby enhancing survival rates [1].

Keap1-Nrf2-IN-21 (compound 4d) acts as an inhibitor of glucose metabolism with anti-tumoral properties. It targets the glycolytic pathway by affecting the Keap1-Nrf2 signaling pathway, which in turn suppresses glycolytic activity in cancer cells and inhibits tumor growth. Additionally, Keap1-Nrf2-IN-21 exhibits cytotoxic effects on the HEC1A cell line with an IC50 value of 2.60 μM.

1. Farrerol has antioxidative activity.2. Farrerol modulates TAP and BNBD5 gene expression in mammary gland, enhances bMEC defense against S. aureus infection and could be useful in protection against bovine mastitis. 3. Farrerol inactivates KEAP-1 or act