mpo inhibitor azm198  (Sugen Inc)

Journal: Kidney International

Article Title: Myeloid expression of the anti-apoptotic protein Mcl1 is required in anti-myeloperoxidase vasculitis but myeloperoxidase inhibition is not protective

doi: 10.1016/j.kint.2022.08.028

Figure Lengend Snippet: AZD5904-, AZM198-, or vehicle-treated mice after injection of anti-myeloperoxidase antibody with glomerular colony-stimulating factor. ( a ) Quantification of glomerular crescents. ( b,c ) Quantification of intraglomerular and periglomerular CD68-positive cells. ( d ) Quantification of glomerular neutrophils. ( e,f ) Biochemical parameters of disease, showing day 7 serum creatinine and day 6 albuminuria. Data for 1 baseline urine are missing from the AZM198-treated group for technical reasons. Data in ( a )–( d ) and ( f ), and the day 6 urine albumin–creatinine ratios in ( e ) were analyzed with a 1-way analysis of variance (ANOVA) and Dunnett's multiple comparisons test, as were the baseline urine albumin–creatinine ratios. A 2-way ANOVA with Šídák's multiple comparisons test was used to compare baseline and day 6 urine albumin–creatinine ratios. Each symbol represents data from an individual mouse. Error bars are mean ± SD. ∗∗ P < 0.01, ∗∗∗ P < 0.001, and ∗∗∗∗ P < 0.0001.

Article Snippet: The MPO inhibitors AZD5904 or AZM198 (AstraZeneca) were suspended in the vehicle 0.5% hydroxypropyl methylcellulose and 0.1% Tween-80 (Sigma).

Techniques: Injection

Journal: Kidney International

Article Title: Myeloid expression of the anti-apoptotic protein Mcl1 is required in anti-myeloperoxidase vasculitis but myeloperoxidase inhibition is not protective

doi: 10.1016/j.kint.2022.08.028

Figure Lengend Snippet: Human neutrophil extracellular trap (NET) formation after activation with phorbol 12-myristate 13-acetate. ( a ) Neutrophils from 3 healthy donors were treated with control, AZD5904, or AZM198. ( b ) Representative images in control and AZD5904- or AZM198-treated neutrophils. Data were analyzed with a 1-way analysis of variance and Dunnett's multiple comparisons test. ∗ P < 0.05. Bars = 20 μm. To optimize viewing of this image, please see the online version of this article at www.kidney-international.org .

Article Snippet: The MPO inhibitors AZD5904 or AZM198 (AstraZeneca) were suspended in the vehicle 0.5% hydroxypropyl methylcellulose and 0.1% Tween-80 (Sigma).

Techniques: Activation Assay

Journal: Journal of Leukocyte Biology

Article Title: Oxidation of bacillithiol during killing of Staphylococcus aureus USA300 inside neutrophil phagosomes

doi: 10.1002/JLB.4HI1021-538RR

Figure Lengend Snippet: BSH oxidation during neutrophil phagocytosis is dependent on MPO activity. Neutrophils (5 × 10 6 /ml in HBSS with 10% serum) were pretreated at 37°C for 5 min with the MPO inhibitors AZM198 (10 μM) and azide (100 μM), and methionine (0.5 mM) before mixing with serum‐opsonized S. aureus USA300 WT (LB‐stat, 5 × 10 7 CFU/ml). BSH levels were determined by LC–MS in total cell lysates after a 30 min incubation. Each data point is from one of three independent experiments using different blood donors as indicated by symbol shape. The error bar represents the mean + sd . Significant differences (* p < 0.05) compared with untreated neutrophils and bacteria (gray bar) were identified by repeated measures ANOVA with Dunnett's multiple comparison test. When compared with bacteria alone, only the sample containing untreated neutrophils and bacteria, that is, the gray bar, revealed statistically significant differences in BSH levels.

Article Snippet: The specific MPO inhibitors TX1 and AZM198, 2‐thioxanthine molecules, were provided by AstraZeneca (Mölndal, Sweden).

Techniques: Activity Assay, Liquid Chromatography with Mass Spectroscopy, Incubation, Bacteria, Comparison