Journal: Life

Article Title: Modulation of Oxidative and ER Stress Pathways by the ADAM17 Inhibitor GW280264X in LPS-Induced Acute Liver Injury

doi: 10.3390/life15121877

Figure Lengend Snippet: Effects of GW280264X on redox regulatory proteins in liver tissue. ( A ) Kelch-like ECH-associated protein 1 (Keap1), ( B ) nuclear factor erythroid 2 2-related factor 2 (Nrf2), and ( C ) glutathione (GSH) levels. Data are presented as mean ± SEM ( n = 5). * p < 0.05 vs. 0.9% NaCl, # p < 0.05 vs. LPS. Black squares represent individual data points for each animal.

Article Snippet: Commercial ELISA kits were used to quantify liver tissue levels of KEAP1 (Cat. No. E2198Mo, BT-Laboratory, Shanghai, China), CHOP (Cat. No. E2718Mo, BT-Laboratory), 4-HNE (Cat. No. E1293Mo, BT-Laboratory), MDA (Cat. No. E0625Mo, BT-Laboratory), NRF2 (Cat. No. E1367Mo, BT-Laboratory), TNF-α (Cat. No. E-EL-M3063, Elabscience, Houston, TX, USA), GRP78 (Cat. No. E-EL-M2696, Elabscience, Houston, TX, USA), glutathione (GSH) colorimetric assay kit (Cat No. E-EL-0026, Elabscience, Houston, TX, USA) and ATF6 (Cat. No. ELK4479, Elk Biotechnology, Wuhan, China).

Techniques:

Journal: Natural Product Communications

Article Title: Yougui Pills Alleviates Diminished Ovarian Reserve Through Regulating Oxidative Stress and Apoptosis in Rats

doi: 10.1177/1934578x241296409

Figure Lengend Snippet: Figure 4. YGP reduced oxidative stress by regulating Keap1/Nrf2. The protein levels of (A and B) Keap1, (A and C) Nrf2, (A and D) SOD2, (A and E) NQO1 and (A and F) NOX4 were determined using immunoblots. ##P < .01, ###P < .001 model group versus control group, *P < .05, **P < .01, ***P < .001 versus model group.YGP: Yougui pill.

Article Snippet: Enzyme-linked immunosorbent assay kits for FSH (MM-70867R1), LH (MM-0624R1), AMH (MM-0219R1), and Cortisol (MM-0574R1) were obtained from Wuhan Bioqiandu Technology Co., Ltd. Primary antibodies of Keap1 (1:1000, WL02135), Nrf2 (1:1000, WL02117), SOD2 (1:1000, WL02506), NQO1 (1:1000, WL04860), Bcl-2 (1:1000, WL01556), Bax (1:1000, WL01637), and Caspase3 (1:1000, WL02117), β-tubulin (1:1000, WL01931), and antirabbit secondary antibody (1:2000, WLA023) were purchased from Wanlei Biochemical Technology Co., Ltd. NOX4 (1:1000, 14347-1-AP) was purchased from proteintech.

Techniques: Western Blot, Control

Journal: Journal of medicinal chemistry

Article Title: Isoquinoline Kelch-like ECH-Associated Protein 1-Nuclear Factor (Erythroid-derived 2)-like 2 (KEAP1-NRF2) Inhibitors with High Metabolic Stability

doi: 10.1021/acs.jmedchem.9b01074

Figure Lengend Snippet: Under basal conditions, NRF2 is bound to KEAP1, ubiquitinated by CUL3, and degraded by the proteasome (top). In the presence of an electrophile (middle) or a non-covalent inhibitor (bottom), NRF2 translocates to the nucleus and transcribes cytoprotective genes, like NADPH quinone oxidoreductase 1 (NQO1), heme oxygenase-1 (HO-1), and glutathione S-transferase (GST).

Article Snippet: 19 – 20 Other non-electrophilic NRF2 activators have been reported by groups at Sanofi ( 6 ) 21 and GlaxoSmithKline/Astex ( 7 ) 22 – 23 and are shown in .

Techniques:

Journal: Journal of medicinal chemistry

Article Title: Isoquinoline Kelch-like ECH-Associated Protein 1-Nuclear Factor (Erythroid-derived 2)-like 2 (KEAP1-NRF2) Inhibitors with High Metabolic Stability

doi: 10.1021/acs.jmedchem.9b01074

Figure Lengend Snippet: IC 50 , logD 7.4 , and Metabolic t 1/2 of Isoquinoline NRF2 Activators

Article Snippet: 19 – 20 Other non-electrophilic NRF2 activators have been reported by groups at Sanofi ( 6 ) 21 and GlaxoSmithKline/Astex ( 7 ) 22 – 23 and are shown in .

Techniques:

Journal: Journal of medicinal chemistry

Article Title: Isoquinoline Kelch-like ECH-Associated Protein 1-Nuclear Factor (Erythroid-derived 2)-like 2 (KEAP1-NRF2) Inhibitors with High Metabolic Stability

doi: 10.1021/acs.jmedchem.9b01074

Figure Lengend Snippet: A) HaCaT cells were treated with vehicle control DMSO, 10 μM compound (5e, 12, 5a, 11b, 11c, 13a), or positive control 3 (1 μM) for 16 h. Cell lysates were prepared, equal amounts of protein was probed with antibodies specific for NRF2 or NQO1. Actin was used as a reference. Image was cropped at the dotted line to remove an unrelated compound. See the supplemental information for the uncropped images. NRF2 and NQO1 band intensities were quantified using NIH ImageJ software, and were normalized to that of respective actin band intensity. The normalized values of NRF2 and NQO1 of DMSO-treated samples was taken as one unit. The fold increase in NRF2 and NQO1 expression of two independent sets is presented relative to DMSO controls independently or combined. B) HaCaT cells were treated with DMSO, 0.1, 1, or 10 μM 13a, or 250 nM 3.

Article Snippet: 19 – 20 Other non-electrophilic NRF2 activators have been reported by groups at Sanofi ( 6 ) 21 and GlaxoSmithKline/Astex ( 7 ) 22 – 23 and are shown in .

Techniques: Control, Positive Control, Software, Expressing

Journal: Journal of medicinal chemistry

Article Title: Isoquinoline Kelch-like ECH-Associated Protein 1-Nuclear Factor (Erythroid-derived 2)-like 2 (KEAP1-NRF2) Inhibitors with High Metabolic Stability

doi: 10.1021/acs.jmedchem.9b01074

Figure Lengend Snippet: Quantification of Western Blot Data in Figure 3A .

Article Snippet: 19 – 20 Other non-electrophilic NRF2 activators have been reported by groups at Sanofi ( 6 ) 21 and GlaxoSmithKline/Astex ( 7 ) 22 – 23 and are shown in .

Techniques: Western Blot

Journal: Journal of medicinal chemistry

Article Title: Isoquinoline Kelch-like ECH-Associated Protein 1-Nuclear Factor (Erythroid-derived 2)-like 2 (KEAP1-NRF2) Inhibitors with High Metabolic Stability

doi: 10.1021/acs.jmedchem.9b01074

Figure Lengend Snippet: Quantification of Western Blot Data in Figure 3B .

Article Snippet: 19 – 20 Other non-electrophilic NRF2 activators have been reported by groups at Sanofi ( 6 ) 21 and GlaxoSmithKline/Astex ( 7 ) 22 – 23 and are shown in .

Techniques: Western Blot

Journal: Immunity, Inflammation and Disease

Article Title: Therapeutic potential of dihydroartemisinin in mitigating radiation‐induced lung injury: Inhibition of ferroptosis through Nrf2/HO‐1 pathways in mice

doi: 10.1002/iid3.1175

Figure Lengend Snippet: Effects of DHA on Nrf2 and HO‐1 expressions in lung tissues of various groups of mice. (A) Representative images of IHC staining for Nrf2 in mice lung tissues; (B) AOD of Nrf2 expressions; (C) Western blots for HO‐1 in mice lung tissues; (D) The relative expression of HO‐1 determined by optical densitometry. AOD, average optical density; DHA, dihydroartemisinin; HO‐1, Heme oxygenase‐1; IHC, immunohistochemistry; IOD, Integrated optical density; IR, irradiation; Nrf2, nuclear factor erythroid 2‐related factor 2; IR + DHA, irradiation + DHA. AOD = IOD/Area (%). Black arrow, positive cell. Original magnification 400×. Data are presented as mean ± standard deviation, * p < .05, ** p < .01, *** p < .001, **** p < .0001. Differences in statistical significance between groups were determined by one‐way ANOVA and a Turkey multiple comparisons posttest.

Article Snippet: DHA and Brusatol (Nrf2 inhibitor) were purchased from Tauto.

Techniques: Immunohistochemistry, Western Blot, Expressing, Irradiation, Standard Deviation

Journal: Journal of Medicinal Chemistry

Article Title: E3 Ligases Meet Their Match: Fragment-Based Approaches to Discover New E3 Ligands and to Unravel E3 Biology

doi: 10.1021/acs.jmedchem.2c01882

Figure Lengend Snippet: Fragment hit to lead campaign of KEAP1 by Davies et al. (A) Optimization of fragments 5 , 6 , and 7 to candidate KI-696 (reported cell efficacy corresponds to the level of induction of enzymatic activity of the NRF2-dependent protein, NADPH quinone acceptor oxidoreductase 1 (NQO1), in the human lung epithelial cell line BEAS-2B). (B) Overlay of crystal structures of KEAP1-Kelch domain bound by 5 (PDB entry 5fnq , blue carbons), 6 (PDB entry 5fzj , magenta carbons), 7 (PDB entry 5fzn , yellow carbons), and KI-696 (PDB entry 5fnu , white carbons).

Article Snippet: In 2016, scientists at Astex and GSK disclosed the first fragment screen against KEAP1 that was aimed at identifying new hits that could eventually be optimized to inhibitors with improved properties over the existing equity.

Techniques: Activity Assay

Journal: Journal of Medicinal Chemistry

Article Title: E3 Ligases Meet Their Match: Fragment-Based Approaches to Discover New E3 Ligands and to Unravel E3 Biology

doi: 10.1021/acs.jmedchem.2c01882

Figure Lengend Snippet: PROTACs containing the scaffold of the KEAP1 inhibitor KI-696 .

Article Snippet: In 2016, scientists at Astex and GSK disclosed the first fragment screen against KEAP1 that was aimed at identifying new hits that could eventually be optimized to inhibitors with improved properties over the existing equity.

Techniques:

Journal: Journal of Medicinal Chemistry

Article Title: E3 Ligases Meet Their Match: Fragment-Based Approaches to Discover New E3 Ligands and to Unravel E3 Biology

doi: 10.1021/acs.jmedchem.2c01882

Figure Lengend Snippet: KEAP1 FBDR study by Pallesen et al. giving rise to reconstructed inhibitors such as 46 with nM K i and a novel binding mode to the Kelch domain of KEAP1. Crystal structures shown: left panel, KEAP1 bound by 45 (PDB entry 6zey ); right panel, KEAP1 bound by 46 (PDB entry 6zf8 ). Structures have been aligned and are shown in the same orientation. FP K i data for inhibitors 43 and 44 have been disclosed in a previous report by the same authors.

Article Snippet: In 2016, scientists at Astex and GSK disclosed the first fragment screen against KEAP1 that was aimed at identifying new hits that could eventually be optimized to inhibitors with improved properties over the existing equity.

Techniques: Binding Assay