Generation of Novel Anti-MUC1 Monoclonal Antibodies with Designed Carbohydrate Specificities Using MUC1 Glycopeptide Library.

Numerous anti-mucin 1 (anti-MUC1) antibodies that recognize -glycan core structures have already been developed. However, most of them show low specificities toward -glycan structures and/or low affinity toward a monovalent epitope. In this study, using an MUC1 glycopeptide library, we established two novel anti-MUC1 monoclonal antibodies (1B2 and 12D10) with designed carbohydrate specificities.

Convergent Solid-Phase Synthesis of Macromolecular MUC1 Models Truly Mimicking Serum Glycoprotein Biomarkers of Interstitial Lung Diseases.

Synthetic macromolecular MUC1 glycopeptides have been used to unravel molecular mechanisms in antibody recognition of disease-specific epitopes. We have established a novel synthetic strategy for MUC1 tandem repeats having complex O-glycosylation states at each repeating unit based on convergent solid-phase fragment condensation under microwave irradiation. We have accomplished the synthesis of 77 amino acid MUC1 glycopeptides (MW = 12 759) having three major antigenic O-glycoforms [Tn, core 1 (T), and core 2 structures] at 10 designated positions out of 19 potential O-glycosylation sites.

Plasma miR-208 as a useful biomarker for drug-induced cardiotoxicity in rats.

Cardiotoxicity is one of the major safety concerns in drug development. Therefore, detecting and monitoring cardiotoxicity throughout preclinical and clinical studies is important for pharmaceutical companies. The present study was conducted in order to explore a plasma miRNA biomarker for cardiotoxicity in rats.

Genomic biomarkers for cardiotoxicity in rats as a sensitive tool in preclinical studies.

The development of safer drugs is a high priority for pharmaceutical companies. Among the various toxicities caused by drugs, cardiotoxicity is an important issue because of its lethality. In addition, cardiovascular toxicity leads to the attrition of many drug candidates in both preclinical and clinical phases.

[Toxicity study of cefmatilen hydrochloride hydrate (S-1090) (2)--Single oral dose toxicity study in dogs].

Cefmatilen hydrochloride hydrate (S-1090) was administered at 500 and 1000 mg potency/kg once orally to beagle dogs. No deaths occurred. Vomiting, diarrhea or mucous feces occurred on the dosing day, and reddish-brown feces (due to chelated products of S-1090 and its decomposition products with Fe3+ in the diet) were also observed on the dosing and next day.

[Toxicity study of cefmatilen hydrochloride hydrate (S-1090) (4)--One- and three-month repeated oral dose toxicity studies in dogs].

One- or three-month repeated oral dose toxicity studies of Cefmatilen hydrochloride hydrate (S-1090) were conducted in beagle dogs. Doses were set at 25, 100 and 400 mg potency/kg/day in both studies. In both studies, no deaths occurred, and reddish-brown feces (due to chelated products of S-1090 and its decomposition products with Fe3+ in the diet) were observed in all treated groups.

[Toxicity study of cefmatilen hydrochloride hydrate (S-1090) (8)--Nephrotoxicity study in rabbits by single oral administration].

A nephrotoxicity study of Cefmatilen hydrochloride hydrate (S-1090) was conducted in rabbits at single oral doses of 250, 500 and 1000 mg potency/kg. All treated groups showed a decreased food consumption and a tendency for the body weight to decrease. Urinary protein and glucose were detected and slight increases of plasma creatinine and urea nitrogen were observed in the 500 mg potency/kg group.

[Toxicity study of cefmatilen hydrochloride hydrate (S-1090) (3)--One- and three-month repeated oral dose toxicity studies in rats].

One- or three-month repeated oral dose toxicity studies of Cefmatilen hydrochloride hydrate (S-1090) in rats were conducted. Doses were set at 80, 200, 500 and 1250 mg potency/kg/day in the one-month toxicity study, and 100, 300 and 1000 mg potency/kg/day in the three-month toxicity study. Body weights increased favorably and no deaths occurred in all treated groups of both studies.

[Toxicity study of cefmatilen hydrochloride hydrate (S-1090) (1)--Single oral and intravenous dose toxicity studies in rats].

A single oral dose toxicity study of Cefmatilen hydrochloride hydrate (S-1090) and a single intravenous dose toxicity study of its sodium salt (S-1090-Na) were conducted in rats. One dose level of 2000 mg potency/kg was set in both studies. Single oral dose toxicity study of S-1090 No deaths occurred.