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

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-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-27 is an inhibitor of the Keap1-Nrf2 protein-protein interaction (PPI) with a KD2 value of 0.119 μM. It suppresses the expression of pro-inflammatory cytokines TNF-α and IL-6 in an LPS-induced RAW264.7 cell model.

Keap1-Nrf2-IN-28 (SG16) is an orally active inhibitor of Keap1-Nrf2. It demonstrates antioxidant properties and upregulates the expression of Nrf2, HO-1, GCLM, and Akr1c1. Additionally, Keap1-Nrf2-IN-28 can mitigate acute liver injury induced by APAP.

Keap1/Nrf2/ARE activator 1 (compound HT-3) functions as an activator of the Keap1/Nrf2/ARE pathway. This compound has antioxidant properties and offers neuroprotective effects.

Keap1-Nrf2-IN-17 (compound 18) is a potent inhibitor of the protein-protein interaction between Keap1 and Nrf2.

Keap1-Nrf2-IN-18 (Compound 22) is an orally active inhibitor of the Keap1-Nrf2 protein-protein interaction (PPI), demonstrating favorable pharmacokinetic (PK) properties and enhanced in vivo efficacy in rats. In structure-activity relationship (SAR) studies, Keap1-Nrf2-IN-18 exhibits the strongest inhibitory activity (KD = 0.0029 μM).

Keap1-Nrf2-IN-19 (compound 33) is an orally active inhibitor of the Keap1-Nrf2 protein-protein interaction (PPI), with a Kd value of 0.0014 μM. Keap1-Nrf2-IN-19 exhibits less than 50% inhibition of hERG at 30 μM and CYPs at 10 μM.

Keap1-IN-2 (Compound 164) is an inhibitor of KEAP1 with an IC50 of 2 nM. It indirectly activates Nrf2 by blocking KEAP1, thereby enhancing cellular antioxidant capacity. By preventing KEAP1-mediated degradation of Nrf2, Keap1-IN-2 promotes the accumulation and nuclear translocation of Nrf2. This compound is used in research on diseases related to oxidative stress, such as inflammatory bowel disease, Crohn's disease, and ulcerative colitis, which are immune-related conditions.

Keap1-Nrf2-IN-29 (Compound 1a), a Curcumin analog, functions as an inhibitor of the Keap1 protein. It demonstrates significant inhibitory activity against A549, PC-3, and MCF-7 cells. Keap1-Nrf2-IN-29 is applicable for prostate cancer research.

Keap1/Nrf2/ARE activator 2 is an activator of the Keap1/Nrf2/ARE pathway, acting as a non-competitive inhibitor of AChE with an IC50 of 14.79 μM and a Ki of 1.35 μM. It enhances Nrf2 nuclear translocation, thereby upregulating antioxidant gene expression and boosting cellular defenses against oxidative stress. In PC12 cells, Keap1/Nrf2/ARE activator 2 demonstrates significant neuroprotective effects against damage induced by H2O2 and Scopolamine (SCA). In zebrafish models, it alleviates cognitive deficits and neuroinflammation associated with SCA-induced impairments. This compound is relevant for Alzheimer's disease research.

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.