Keap1-Nrf2 Inhibitor

KEAP1-NRF2 PPI-IN-1 (compound 23) is an inhibitor targeting the KEAP1-NRF2 interaction. KEAP1-NRF2 PPI-IN-1 has IC₅₀ values of 136 nM and 62 nM in the DNA damage assays of human TK6 and insect SF9 cell lines, respectively.

Keap1-Nrf2-IN-6 (compound 64) is a potent and selective Keap1-Nrf2 PPI (Keap1-Nrf2 protein−protein interaction) inhibitor with an IC₅₀ of 41 nM, K_d of 68 nM.

CD-10 is an orally active and BBB-penatrable Keap1-Nrf2 protein-protein interaction (PPI) inhibitor. CD-10 binds to Keap1 with a K_D value of 193 nM. CD-10 exhibits potent anti-oxidative and anti-inflammatory effects through Keap1-Nrf2 pathway activation, evidenced by reduced levels of MDA, IL-4, IL-10 and increased expression of HO-1. CD-10 effectively alleviated anxiety and depressive behaviors and restored serum neurotransmitter levels by promoting Nrf2 nuclear translocation in the chronic unpredictable mild stress (CUMS) mouse model. CD-10 can be used for the study of depression.

Keap1-Nrf2-IN-11 (compound 6k) is a Keap1-Nrf2 inhibitor with K_D2 value of 0.21 nM. Keap1-Nrf2-IN-11 inhibits the productions of ROS and NO and the expression of TNF-α. Keap1-Nrf2-IN-11 relieves inflammations by increasing the Nrf2 nuclear translocation. Keap1-Nrf2-IN-11 can be used for anti-inflammatory research.

S27-1047 is a brain-penetrant, potent and selective BChE (eqBChE IC₅₀ = 7.16 nM; hBChE IC₅₀ = 296.10 nM) inhibitor and Nrf2 activator. S27-1047 can directly bind Keap1, disrupt Keap1-Nrf2 interaction (FP IC₅₀ = 36.87 nM), enhance antioxidant enzyme expression and activate the GSH-GPX4 axis to inhibit Aβ-induced ferroptosis. S27-1047 can protect against oxidative stress and neuroinflammation. S27-1047 can be used in Alzheimer's disease research.

Keap1-Nrf2-IN-8 (compound 12d) is a potent Keap1-Nrf2 PPI (Keap1-Nrf2 protein−protein interaction) inhibitor with IC₅₀s of 64.5 nM and 14.2 nM for FP and TR-FRET assays, respectively. Keap1-Nrf2-IN-8 significantly increases the mRNA levels of Nrf2 downstream genes, GSTM3, HMOX2 and NQO1.

Dehydrobruceine B, a quassinoid, can be isolated from Brucea javanica. Dehydrobruceine B shows a synergistic effect with Cisplatin (HY-17394) to induce apoptosis via mitochondrial method. Dehydrobruceine B increases apoptosis-inducing factor (AIF) and Bax expression and suppresses Keap1-Nrf2.

Keap1-Nrf2-IN-15 (Compound 24a) is a potent Keap1-Nrf2 protein-protein interaction inhibitor with IC₅₀s of 77 nM and 2.5 nM in FP assay and TR-FRET assay, respectively.

Keap1-Nrf2-IN-12 is a potent Keap1-Nrf2 inhibitor with an IC₅₀ value of 2.30 µM. Keap1-Nrf2-IN-12 shows metabolic stability in human liver microsomes.

Pirimiphos ethyl (Standard) is the analytical standard of Pirimiphos ethyl. This product is intended for research and analytical applications. Pirimiphos ethyl is a kind of organophosphorus pesticide that commonly employes for the protection of crops including vegetables, bananas, turf and mushrooms through the inhibition of acetylcholinesterase activity.

Keap1-Nrf2-IN-30 is an orally active, blood-brain barrier-permeable Keap1-Nrf2 protein-protein interaction inhibitor with a Keap1 K_d value of 157 nM. Keap1-Nrf2-IN-30 selectively inhibits the Keap1-Nrf2 protein-protein interaction, promotes Nrf2 nuclear translocation, suppresses induced ferroptosis, reduces the expression of Aβ and p-Tau, and upregulates the expression of GPX4 and SLC7A11. Keap1-Nrf2-IN-30 upregulates the expression of HO-1 and NQO1, alleviates neuronal damage, and improves cognitive and spatial memory deficits. Keap1-Nrf2-IN-30 can be used in the research of Alzheimer's disease.

Anticonvulsant agent 10 (Compound 6d) is an inhibitor targeting the Keap1-Nrf2 interaction, with a potent ED₅₀ of 0.04 mmol/kg. By inhibiting Keap1-Nrf2 binding and activating the Nrf2/ARE pathway, Anticonvulsant agent 10 exerts anticonvulsant and neuroprotective effects, making it suitable for research in antiepileptic and neuroprotective studies.

NBE5 is an orally active hydrophobic tag-targeting (Hyt) degrader (HyTTD) that targets Keap1. NBE5 mimics protein misfolding and recruits the molecular chaperone Hsp90, while achieving targeted degradation of Keap1 through both the ubiquitin-proteasome system and the autophagy-lysosome system. Consequently, NBE5 relieves the inhibition of the transcription factor Nrf2 by Keap1, potently activates the Nrf2-mediated endogenous antioxidant pathway, and upregulates the expression of downstream antioxidant proteins such as HO-1 and GCLM. NBE5 effectively alleviates oxidative stress and inflammatory damage, and exhibits excellent in vivo activity in a mouse model of acute colitis induced by DSS (HY-116282C).
NBE5 consists of a hydrophobic tag (HY-W022007), a Keap1-Nrf2 ligand (HY-14909), and a linker (HY-W014831).

Nrf-2/HMOX-1-IN-1 is a Nrf-2 and HMOX-1 inhibitor, as well as a Ferroptosis inducer. Nrf-2/HMOX-1-IN-1 inhibits GPX activity and upregulates p53 gene expression. Nrf-2/HMOX-1-IN-1 increases intracellular ROS and MDA levels, reduces GSH content, and elevates intracellular iron levels simultaneously. Nrf-2/HMOX-1-IN-1 exerts selective anticancer effects against breast cancer. Nrf-2/HMOX-1-IN-1 can be used in breast cancer-related research.

Keap1-Nrf2-IN-29 (Compound 1a), a Curcumin (HY-N0005) analog, is a Keap1 protein inhibitor. Keap1-Nrf2-IN-29 exhibits significant inhibitory activity against A549, PC-3 and MCF-7 cells. Keap1-Nrf2-IN-29 can be used for the study of prostate cancer.

Isorhapontigenin (Standard) is the analytical standard of Isorhapontigenin (HY-N2593). This product is intended for research and analytical applications. Isorhapontigenin is an orally active dietary polyphenol. Isorhapontigenin acts as a potent antioxidant that reduces the production of reactive oxygen species (ROS). Isorhapontigenin promotes the binding of JUN to the AP-1 site on the SESN2 promoter, induces SESN2 transcription, triggers MAPK8-dependent JUN activation, and upregulates the expression of PPAR-α, PGC-1α and CPT-1A to facilitate fatty acid oxidation. Isorhapontigenin induces autophagy, apoptosis and preadipocyte differentiation; it inhibits tumor growth, cell invasion, NF-κB transcriptional activity, the PI3K/Akt signaling pathway, STAT1 phosphorylation and MMP-2 expression. Isorhapontigenin alleviates oxidative stress, inflammatory cytokine release and triglyceride accumulation; it increases intracellular ATP levels and promotes Nrf2 nuclear translocation. Isorhapontigenin improves insulin sensitivity in adipose tissue and glucose tolerance, and reduces postprandial blood glucose, insulin and free fatty acid levels. Isorhapontigenin is applicable to research on bladder cancer, liver injury, chronic obstructive pulmonary disease, acute lung injury and type 2 diabetes.

Keap1-p-p62-IN-1 is a potent and selective Keap1-p-p62 inhibitor with an IC₅₀ of 0.11 μM. Keap1-p-p62-IN-1 shows 18.73-fold selectivity over Keap1-Nrf2 interaction. Keap1-p-p62-IN-1 normalizes Nrf2 ubiquitination, sensitizes cells to Sorafenib (HY-10201)-induced ferroptosis. Keap1-p-p62-IN-1 can be used for the research of p62 aberrant hepatocellular carcinoma.

Keap1-Nrf2-IN-22 (compound 19) is a Keap1-Nrf2 inhibitor， with a K_D2 value of 42.2 nM for Keap1. Keap1-Nrf2-IN-22 can be used for the study of acute lung injury (ALI) and cerebral ischemia/reperfusion (I/R) injury.

Keap1-Nrf2-IN-25 (Compound 19) is a potent Keap1-Nrf2 inhibitor (IC₅₀ of 0.55 μM) with Keap1 binding affinity (K_d of 0.50 μM). Keap1-Nrf2-IN-25 activates Nrf2, reduces ROS and pro-inflammatory cytokines (IL-1β, IL-6). Keap1-Nrf2-IN-25 exerts protective effects against DSS (HY-116282)-induced colitis.

4-Methoxychalcone is a naturally occurring chalcone compound. 4-Methoxychalcone has antioxidant activity, anti-inflammatory activity, antitumor activity and antibacterial activity. 4-Methoxychalcone can be used to study inflammation and tumor models.