Journal: Frontiers in Pharmacology

Article Title: Alphataxin, an Orally Available Small Molecule, Decreases LDL Levels in Mice as a Surrogate for the LDL-Lowering Activity of Alpha-1 Antitrypsin in Humans

doi: 10.3389/fphar.2021.695971

Figure Lengend Snippet: All 5 Classes of β-Lactams Bind to HLE-G and HLE-CS.

Article Snippet: The following representatives of the five classes of β-lactams were screened for activity: I Cephalosporins (Cephems) 1) Cephalexin (CAS# 15686-71-2, 347.4 mw) (Cayman Chemical 9002009, batch 0462553-11) 2) Cefuroxime (CAS# 55268-75-2, 424.39 mw) (SigmaAldrich 34218-100 mg, batch SZBE050XV) II Penicillins (Penams) 1) D-Ampicillin (CAS# 63-53-4, 349.4 mw) (SigmaAldrich A9393-5 g, batch 086M4774V) 2) Penicillin V (CAS# 87-08-1, 350.39 mw) (SigmaAldrich 1504489-200 mg, batch R05030) 3) Dicloxacillin (CAS# 3116-76-5, 492.31 mw) (SigmaAldrich 46182-100 mg, batch SZBD263XV) 4) Amoxicillin (CAS# 34642-77-8, 365.40 mw) (SigmaAldrich A8523-1G, batch 066M4760V) 5) Alphataxin (CAS#19379-33-0, 349.4 mw) (BOC Sciences, batch B17LM02161) III Monobactams 1) Aztreonam (CAS# 78110-38-0, 435.43 mw) (SigmaAldrich A6848-50 mg, batch MKBW2997V) 2) Ezetimibe (CAS# 163222-33-1, 409.43 mw) (SigmaAldrich 1269028-250 mg, batch F028D0) IV Penems 1) Faropenem (CAS# 122547-49-3, 307.30 mw) (SigmaAldrich F8182-10 mg, batch 0000016430) V Carbapenems 1) Doripenem (CAS# 148016-81-3, 420.50 mw) (SigmaAldrich 32138-25 mg, batch BCBR7602V) Antibiotic activity .

Techniques: Concentration Assay

Journal: Frontiers in Pharmacology

Article Title: Alphataxin, an Orally Available Small Molecule, Decreases LDL Levels in Mice as a Surrogate for the LDL-Lowering Activity of Alpha-1 Antitrypsin in Humans

doi: 10.3389/fphar.2021.695971

Figure Lengend Snippet: Lack of Antibiotic Activity by Alphataxin. D-Ampicillin-sensitive E. coli DH5-Alpha, calibrated using McFarland Turbidity Standard 0.05 for <300 × 10 6 CFU, was spread on Mueller-Hinton agar plates. Filter disks (6 mm diameter) were placed on the agar and to each disk was applied D-ampicillin (10 μl) or Alphataxin (10 μl) in 10-fold serial dilutions, counterclockwise, beginning with 50 mM concentration. After incubation for 16 h at 37°C, plates were examined for zones of inhibition (clear agar). (A) The diameters of the zones of inhibition by D-ampicillin at concentrations of 50 mM (12 o’clock), 5 mM (10 o’clock), and 0.05 mM (8 o’clock) were 3.8, 3.0, and 1.4 cm, respectively. (B) The diameters of the zones of inhibition by Alphataxin at 50 mM (at 12 o’clock) and 5 mM (10 o’clock) were 2.8 and 1.5 cm, respectively. Images are representative of two repeated experiments.

Article Snippet: The following representatives of the five classes of β-lactams were screened for activity: I Cephalosporins (Cephems) 1) Cephalexin (CAS# 15686-71-2, 347.4 mw) (Cayman Chemical 9002009, batch 0462553-11) 2) Cefuroxime (CAS# 55268-75-2, 424.39 mw) (SigmaAldrich 34218-100 mg, batch SZBE050XV) II Penicillins (Penams) 1) D-Ampicillin (CAS# 63-53-4, 349.4 mw) (SigmaAldrich A9393-5 g, batch 086M4774V) 2) Penicillin V (CAS# 87-08-1, 350.39 mw) (SigmaAldrich 1504489-200 mg, batch R05030) 3) Dicloxacillin (CAS# 3116-76-5, 492.31 mw) (SigmaAldrich 46182-100 mg, batch SZBD263XV) 4) Amoxicillin (CAS# 34642-77-8, 365.40 mw) (SigmaAldrich A8523-1G, batch 066M4760V) 5) Alphataxin (CAS#19379-33-0, 349.4 mw) (BOC Sciences, batch B17LM02161) III Monobactams 1) Aztreonam (CAS# 78110-38-0, 435.43 mw) (SigmaAldrich A6848-50 mg, batch MKBW2997V) 2) Ezetimibe (CAS# 163222-33-1, 409.43 mw) (SigmaAldrich 1269028-250 mg, batch F028D0) IV Penems 1) Faropenem (CAS# 122547-49-3, 307.30 mw) (SigmaAldrich F8182-10 mg, batch 0000016430) V Carbapenems 1) Doripenem (CAS# 148016-81-3, 420.50 mw) (SigmaAldrich 32138-25 mg, batch BCBR7602V) Antibiotic activity .

Techniques: Activity Assay, Concentration Assay, Incubation, Inhibition

Journal: Frontiers in Pharmacology

Article Title: Alphataxin, an Orally Available Small Molecule, Decreases LDL Levels in Mice as a Surrogate for the LDL-Lowering Activity of Alpha-1 Antitrypsin in Humans

doi: 10.3389/fphar.2021.695971

Figure Lengend Snippet: Stimulation of Cellular Locomotion and Endocytosis by Alphataxin. U937 Clone 10 cells were preconditioned with α1PI, Alphataxin, or buffer at 37°C for 15 min to induce polarization and receptor aggregation followed by incubation with SHIV at either 2°C or 37°C for 2 h. Cells were adhered to Alcian blue-coated slides and imaged by epifluorescence microscopy using a Zeiss Axioplan. Representative images were captured by confocal microscopy with a Perkin Elmer Operetta High Content Imaging System using 2 μm scanning from the attached surface toward the unattached surface. The three representative confocal images depicted were captured 6 μm above the attached surface of the cells. (A) Cells maintained at 2°C. Arrows denote receptor polarization. SHIV (bright green) was detected only on the exterior plasma membrane of polarized cells, never internal to the cells. (B) Cells maintained at 37°C. Arrows denote the leading edge and retracting trailing edge. SHIV (bright green) was detected internal to the cells at the leading edges (green tubes) and in endosomes (green dots) at the trailing edges of migrating cells. (C) Cells preconditioned with buffer alone and maintained at 2°C showing no SHIV binding. Bar represents 25 µm. Images are representative of 3 repeated experiments.

Article Snippet: The following representatives of the five classes of β-lactams were screened for activity: I Cephalosporins (Cephems) 1) Cephalexin (CAS# 15686-71-2, 347.4 mw) (Cayman Chemical 9002009, batch 0462553-11) 2) Cefuroxime (CAS# 55268-75-2, 424.39 mw) (SigmaAldrich 34218-100 mg, batch SZBE050XV) II Penicillins (Penams) 1) D-Ampicillin (CAS# 63-53-4, 349.4 mw) (SigmaAldrich A9393-5 g, batch 086M4774V) 2) Penicillin V (CAS# 87-08-1, 350.39 mw) (SigmaAldrich 1504489-200 mg, batch R05030) 3) Dicloxacillin (CAS# 3116-76-5, 492.31 mw) (SigmaAldrich 46182-100 mg, batch SZBD263XV) 4) Amoxicillin (CAS# 34642-77-8, 365.40 mw) (SigmaAldrich A8523-1G, batch 066M4760V) 5) Alphataxin (CAS#19379-33-0, 349.4 mw) (BOC Sciences, batch B17LM02161) III Monobactams 1) Aztreonam (CAS# 78110-38-0, 435.43 mw) (SigmaAldrich A6848-50 mg, batch MKBW2997V) 2) Ezetimibe (CAS# 163222-33-1, 409.43 mw) (SigmaAldrich 1269028-250 mg, batch F028D0) IV Penems 1) Faropenem (CAS# 122547-49-3, 307.30 mw) (SigmaAldrich F8182-10 mg, batch 0000016430) V Carbapenems 1) Doripenem (CAS# 148016-81-3, 420.50 mw) (SigmaAldrich 32138-25 mg, batch BCBR7602V) Antibiotic activity .

Techniques: Incubation, Epifluorescence Microscopy, Confocal Microscopy, Imaging, Clinical Proteomics, Membrane, Binding Assay

Journal: Frontiers in Pharmacology

Article Title: Alphataxin, an Orally Available Small Molecule, Decreases LDL Levels in Mice as a Surrogate for the LDL-Lowering Activity of Alpha-1 Antitrypsin in Humans

doi: 10.3389/fphar.2021.695971

Figure Lengend Snippet: Effects of Diet and Drug Treatment on Cholesterol Levels. (A) To establish the effects of dietary fat on lipoprotein levels in the DIO mouse model, mice were fed a 60% or 10% fat diet (control) for 20 weeks. In mice fed a 60% fat diet, there were significantly higher total cholesterol levels ( p < 0.001, n = 4 mice/diet), HDL levels ( p < 0.001, n = 4 mice/diet), and LDL levels ( p < 0.03, n = 4 mice/diet) than in mice fed a 10% fat diet. There was no difference between diets in triglyceride levels ( p = 0.66, n = 4 mice/diet). (B) Mice on the 60% high-fat diet were treated daily by oral gavage with Zetia (ezetimibe, 10 mg/kg) or Alphataxin (5 mg/kg). To compare the effectiveness of ezetimibe (■) and Alphataxin (■) with vehicle (■), % change from baseline was calculated as [100-(Treatment-Baseline/Baseline*100)]. Data were not normally distributed. Treatment arms were compared one-way Kruskal-Wallis analysis of variance on ranks and the Mann-Whitney Rank Sum Test to determine significance of differences between individual treatment groups. Asterisks designate a statistically significant difference at the designated weeks, * p < 0.05, ** p < 0.01, *** p < 0.001.

Article Snippet: The following representatives of the five classes of β-lactams were screened for activity: I Cephalosporins (Cephems) 1) Cephalexin (CAS# 15686-71-2, 347.4 mw) (Cayman Chemical 9002009, batch 0462553-11) 2) Cefuroxime (CAS# 55268-75-2, 424.39 mw) (SigmaAldrich 34218-100 mg, batch SZBE050XV) II Penicillins (Penams) 1) D-Ampicillin (CAS# 63-53-4, 349.4 mw) (SigmaAldrich A9393-5 g, batch 086M4774V) 2) Penicillin V (CAS# 87-08-1, 350.39 mw) (SigmaAldrich 1504489-200 mg, batch R05030) 3) Dicloxacillin (CAS# 3116-76-5, 492.31 mw) (SigmaAldrich 46182-100 mg, batch SZBD263XV) 4) Amoxicillin (CAS# 34642-77-8, 365.40 mw) (SigmaAldrich A8523-1G, batch 066M4760V) 5) Alphataxin (CAS#19379-33-0, 349.4 mw) (BOC Sciences, batch B17LM02161) III Monobactams 1) Aztreonam (CAS# 78110-38-0, 435.43 mw) (SigmaAldrich A6848-50 mg, batch MKBW2997V) 2) Ezetimibe (CAS# 163222-33-1, 409.43 mw) (SigmaAldrich 1269028-250 mg, batch F028D0) IV Penems 1) Faropenem (CAS# 122547-49-3, 307.30 mw) (SigmaAldrich F8182-10 mg, batch 0000016430) V Carbapenems 1) Doripenem (CAS# 148016-81-3, 420.50 mw) (SigmaAldrich 32138-25 mg, batch BCBR7602V) Antibiotic activity .

Techniques: Control, MANN-WHITNEY