other inhibitors  (ApexBio)

Journal: Antimicrobial Agents and Chemotherapy

Article Title: Relative inhibitory activities of newly developed diazabicyclooctanes, boronic acid derivatives, and penicillin-based sulfone β-lactamase inhibitors against broad-spectrum AmpC β-lactamases

doi: 10.1128/aac.00775-24

Figure Lengend Snippet: MICs of β-lactams for AmpC-producing E. coli TOP10 recombinant strains ^a

Article Snippet: All others inhibitors (TAZ HY-W009168, AVI HY-14879, REL HY-16752, VAB HY-19930, NAC HY-109008, ZID HY-120859, TAN HY-109124, XER HY-136072, DUR HY-117974, EMT HY-103095) were purchased from MedChem Express (Luzern, Switzerland).

Techniques: Recombinant, Produced

Journal: Antimicrobial Agents and Chemotherapy

Article Title: Relative inhibitory activities of newly developed diazabicyclooctanes, boronic acid derivatives, and penicillin-based sulfone β-lactamase inhibitors against broad-spectrum AmpC β-lactamases

doi: 10.1128/aac.00775-24

Figure Lengend Snippet: Determination of the 50% inhibitory concentration (IC 50 ) for β-lactamase inhibitors against AmpC enzymes ^a

Article Snippet: All others inhibitors (TAZ HY-W009168, AVI HY-14879, REL HY-16752, VAB HY-19930, NAC HY-109008, ZID HY-120859, TAN HY-109124, XER HY-136072, DUR HY-117974, EMT HY-103095) were purchased from MedChem Express (Luzern, Switzerland).

Techniques: Concentration Assay

Journal: Advanced Science

Article Title: Targeting Adenosine A2b Receptor Promotes Penile Rehabilitation of Refractory Erectile Dysfunction

doi: 10.1002/advs.202306514

Figure Lengend Snippet: Under normoxic condition, adenosine A2a receptor activation up‐regulates HIF‐1α, and down‐regulates PDE5. A) A7r5 cell viability under NECA stimulation. The cell viability was detected by the CCK‐8 test. B) Representative WB protein bands and statistical analysis of TGF‐β, Smad2/3, p‐Smad2/3, α‐SMA, and Tubulin. C) Relative mRNA expressions of HIF‐1α, PDE5, eNOS, and TGF‐β. D) Representative WB protein bands and statistical analysis of A1, A2a, A2b, and A3 receptors under NECA stimulation. E–H) Relative mRNA expressions of HIF‐1α, PDE5, eNOS, and TGF‐β were analyzed. The A7r5 cells were treated by NECA (3 and 10 µ m ) and adenosine receptor inhibitors (PSB‐36 for the A1 receptor, Istra for the A2a receptor, PSB‐603 for the A2b receptor, and MRS‐1523 for the A3 receptor). I) Representative WB protein bands and statistical analysis of HIF‐1α, PDE5, eNOS, TGF‐β, and Tubulin. The A7r5 cells were treated by NECA (10 µ m ) and A2a receptor inhibitors (Istra). Statistical analysis was performed using an unpaired t‐test or ANOVA. N = 3. * P < 0.05, ** P < 0.01, *** P < 0.001, **** P < 0.0001.

Article Snippet: NECA and all the other inhibitors were purchased from ApexBIO (Houston, TX, USA).

Techniques: Activation Assay, CCK-8 Assay

Journal: Advanced Science

Article Title: Targeting Adenosine A2b Receptor Promotes Penile Rehabilitation of Refractory Erectile Dysfunction

doi: 10.1002/advs.202306514

Figure Lengend Snippet: Under hypoxia, adenosine A2b receptor activation up‐regulates HIF‐1α, and down‐regulates PDE5. A) A7r5 cell viability under NECA stimulation. B) Representative WB protein bands and statistical analysis of A1, A2a, A2b, and A3 receptors. C) Volcano plot visualizing the altered gene expression profiles under the stimulation of NECA. D) Cluster and heatmap of the differentially expressed genes. E–G) HIF‐1, cGMP‐PKG, and cAMP signaling pathways were significantly enriched by GSEA. H) Relative mRNA expressions of HIF‐1α, PDE5, and eNOS. I) Relative mRNA expressions of HIF‐1α, PDE5, and eNOS. The A7r5 cells were treated with NECA (10 µ m ) and adenosine receptor inhibitors. J) Representative WB protein bands and statistical analysis of HIF‐1α, PDE5, and eNOS. The A7r5 cells were treated by NECA (10 µ m ) and A2b receptor inhibitor (PSB‐603). K) Representative WB protein bands and statistical analysis of A2b receptor. The A7r5 cells were treated with adenosine receptor inhibitors. L) Representative WB protein bands and statistical analysis of α‐SMA. M): Representative WB protein bands and statistical analysis of α‐SMA. N) Representative WB protein bands and statistical analysis of HIF‐1α, α‐SMA, PDE5, and A2b receptor. The primary corpus cavernosum smooth muscle cells were treated by NECA (10 µ m ) and A2b receptor inhibitor (PSB‐603). O) Relative mRNA expressions of HIF‐1α, eNOS, PDE5, and A2b receptor. Statistical analysis was performed using an unpaired t‐test or ANOVA. N = 3 or 5. * P < 0.05, ** P < 0.01, *** P < 0.001.

Article Snippet: NECA and all the other inhibitors were purchased from ApexBIO (Houston, TX, USA).

Techniques: Activation Assay, Expressing

Journal: Nature

Article Title: Concurrent inhibition of oncogenic and wild-type RAS-GTP for cancer therapy

doi: 10.1038/s41586-024-07205-6

Figure Lengend Snippet: a , Relationship between the area under the curve (AUC) difference (see ) and negative log-transformed P value (two-sided Wilcoxon test) between cell lines by genotype. Points represent mutated genes. Negative AUC indicates sensitivity; positive AUC indicates resistance. b , RMC-7977 EC 50 according to KRAS genotype. Each dot represents a cell line. The centre line is the median, box limits represent first and third quartiles and whiskers depict the range. The number of cell lines in each group is indicated in parentheses. VUS, variants of unknown significance. c , Blood and tumour concentrations of RMC-7977 (green) and DUSP6 mRNA (blue) for NCI-H441 xenograft tumours following one oral dose of 10 mg kg −1 RMC-7977. Data are mean ± s.e.m. of three biological replicates. d , Mice bearing NCI-H441 CDX tumours treated with 10 mg kg −1 RMC-7977 orally once daily for 28 days. ***Adjusted P value = 0.0002; two-way ANOVA ( n = 8 mice per group) with multiple comparison Dunnett’s test. The dashed line shows the initial average tumour volume. Data are mean ± s.e.m. for eight mice per group. e , KRAS(G12X) xenograft models treated with RMC-7977 (10 mg kg −1 by oral administration) for 4–6 weeks. Data are mean ± s.e.m. of 3–18 mice per group. One data point for LUAD G12C is beyond the axis range. Shaded boxes in the table indicate gene variants. f , Kaplan–Meier analysis of time to tumour size doubling ( n = 90 mice per group) of KRAS G12X mutant models treated with 10 mg kg −1 RMC-7977 orally once daily. g , CDX models treated with vehicle control, SHP2 inhibitor (20 mg kg −1 RMC-4550 orally every 2 days), MEK inhibitor (2.5 mg kg −1 cobimetinib orally once daily), combined SHP2 and MEK inhibitors (20 mg kg −1 RMC-4550 orally every 2 days and 2.5 mg kg −1 cobimetinib orally once daily), or 10 mg kg −1 RMC-7977 orally once daily. NCI-H441 ( KRAS G12V , NSCLC) and HPAC ( KRAS G12D , PDAC) models were treated for 21 days. SW620 ( KRAS G12V , CRC) was treated for 28 days. Data are mean ± s.e.m.; n = 8 mice per group for control and RMC-7977, and n = 10 mice per group for RMC-4550, cobimetinib, and RMC-4550 + cobimetinib.

Article Snippet: Other tool inhibitors were acquired from Selleckchem or MedChemExpress.

Techniques: Transformation Assay, Comparison, Mutagenesis

Journal: Nature

Article Title: Concurrent inhibition of oncogenic and wild-type RAS-GTP for cancer therapy

doi: 10.1038/s41586-024-07205-6

Figure Lengend Snippet: a , Cellular nano-BRET assay showing fold-change IC 50 of disrupting the KRAS:CRAF interaction in U2O2 cells expressing KRAS G12C alone or with the indicated secondary mutation in the SWII domain and treated with RMC-7977 or adagrasib for 4 h. Bars represent mean of n = 3 biological replicates ±s.e.m. b , Western blots of parental NCI-H358 (KRAS G12C , NSCLC) and an adagrasib resistant clone of NCI-H358 cells with a secondary NRAS Q61K mutation. Cells were treated with adagrasib or RMC-7977 for 4 h. c , d , pERK levels (MSD) in NCI-H358 (KRAS G12C , NSCLC) cells expressing exogenous RTK DNA constructs indicated by color (GFP control, EGFR WT EGFR A289V , HER2, FGFR2, or RET M918T , treated with adagrasib ( c ) or RMC-7977 ( d ) for 24 h. e , f , pERK levels (MSD) in MIA PaCa-2 (KRAS G12C , PDAC) cells expressing exogenous RTK fusion DNA constructs indicated by color (GFP control, EML4-ALK, CDC6-RET, FGFR3-TACC3), treated with adagrasib ( e ), or RMC-7977 ( f ) for 24 h. n = 2–4 biological replicates per group, normalized to control. Data shown are representative of independent experiments (NCI-H358 n = 3, MIA PaCa-2: n = 2). g , Pa16C (KRAS G12D , PDAC) cells expressing exogenous MEK1 mutant DNA constructs were treated with the indicated inhibitors for 120 h, and proliferation was measured by Calcein AM. n = 3–5 biological replicates from a single experiment, datapoints represent mean ± s.e.m normalized to control.

Article Snippet: Other tool inhibitors were acquired from Selleckchem or MedChemExpress.

Techniques: Bioluminescence Resonance Energy Transfer, Expressing, Mutagenesis, Western Blot, Construct