Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mitsubishi-Tokyo (formerly Mitsubishi Chemical) is developing MCC-555, a thiazolidinedione peroxisome proliferation activated receptor (PPAR)-gamma agonist, as a potential treatment for type 2 diabetes [204644]. Johnson and Johnson is developing the compound outside of Japan [304271,322655]. As of March 2000, MCC-555 was in phase II trials as an insulin sensitizer, both in Japan and abroad [371091]. Phase I trials have been completed by Mitsubishi-Tokyo in the UK and Japan [304271]. Johnson and Johnson trials have shown that the drug is 3-fold more potent than rosiglitazone in the diabetic mouse model, KK-Ay. MCC-555 activates the PPARgamma target gene, aP2, with greater maximal efficacy than other agonists of this target [322655]. MCC-555 binds PPARgamma transcriptional activity which is highly context-specific, such that it can function as a full or partial agonist, or an antagonist, depending on the cell type or DNA binding site. These transcriptional properties are partially explained by unique partial agonism of coactivator recruitment to PPARgamma. This context-specific activity may contribute to its enhanced hypoglycemic potency in vivo despite reduced affinity for PPARgamma [335218]. In February 1999, ING Barings reported that Mitsubishi Chemical expected peak potential sales of yen100 billion for MCC-555, although analysts regarded this prediction as being excessively high at the time [405416].
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PMID:MCC-555 (Mitsubishi-Tokyo Pharmaceuticals). 1601 5

MCC-555 is a novel thiazolidinedione which reduces plasma glucose concentrations in Type 2 diabetes mellitus models due to enhancement of insulin sensitivity. A highly sensitive and selective quantitative method to accurately determine MCC-555 in rat plasma is crucial to the success of pharmacokinetic studies of MCC-555. To this purpose we have developed and validated a high-throughput method in a 96-well plate format using ultra-fast liquid chromatography (Shimadzu Prominence UFLC system) for the determination of MCC-555 in rat plasma. MCC-555 along with the internal standard resveratrol was extracted from 50 microl of rat plasma by liquid-liquid extraction using ethyl acetate. Baseline separation of MCC-555 and resveratrol was achieved using UFLC technology on a C18 stationary-phase column with 2.2 microm particle size. The influences of flow rate, column temperature and mobile phase pH on chromatographic performance were investigated. Comparing to the conventional HPLC method, UFLC showed many advantages including reduced run time, less solvent consumption and increased sensitivity. The UFLC method was sensitive with a lower limit of quantification of 0.002 microg/ml, with good linearity (r>0.999) over the linear range of 0.002-2.0 microg/ml. The intra- and inter-run precision was less than 8.6% and accuracy ranged from -6.4 to 8.2% for quality control samples. The extraction recovery from plasma was no less than 80%. The validation and sample analysis results show that the method is precise, accurate and well suited to support pharmacokinetic studies in rats involving three dose administrations.
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PMID:High-throughput quantification of a novel thiazolidinedione MCC-555 in rat plasma by ultra-fast liquid chromatography and its application in pharmacokinetic studies. 1920 16

MCC-555, a treatment candidate for type 2 diabetes, is a novel thiazolidinedione which has comparatively high anti-diabetic efficacy. The present study was conducted to evaluate its toxicity and toxicokinetics in beagle dogs by oral administration at doses of 0, 6.67, 20 or 40mg/kg/day for 270 days. A 30-day recovery period was included at the end of the study to evaluate the reversibility of the toxic effects. During the treatment and recovery periods, the effects of the test agent on mortality, body weight, food consumption, hematology, serum biochemistry, urinalysis, electrocardiogram (ECG), organ weights, bone marrow and histopathology were examined. There were no treatment-related mortalities. Vomiting was observed in dogs receiving 40mg/kg/day during administration, but the dogs recovered within 1h after oral administration. Significant increases in total bilirubin and alkaline phosphatase were observed in dogs receiving the 40mg/kg/day dose during the treatment period, but the levels returned toward normal during the 30-day recovery period. Mild hydropic or fatty degeneration in the liver and inflammatory cell infiltration in the hepatic lobule or portal area was also observed sporadically without a dose-dependent relationship at the end of treatment and recovery periods. The most apparent toxicity in dogs was in the digestive system. However, these toxic effects of MCC-555 were transient and reversible. The accumulation of MCC-555 after 270-day oral administration was not notable at the toxic dose of 40mg/kg/day and the no-observed-adverse-effect level (NOAEL) was 20mg/kg/day. No differences in toxicokinetics of MCC-555 were observed between male and female dogs and no significant accumulation of MCC-555 was observed in tissues after 270 days of repeated treatments. MCC-555 distribution into different organs showed a higher penetration in the liver, kidneys and testes, followed by the ovaries and uterus. Metabolites and the metabolic style of MCC-555 are to be approved.
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PMID:Subchronic toxicity and toxicokinetics of MCC-555, a novel thiazolidinedione, after 270-day repeated oral administration in dogs. 2178 46

Physical inactivity among older adults around the world is a growing concern. In the United States, older African Americans report high levels of physical inactivity, especially older African Americans with chronic conditions. This study examined the influence of chronic conditions on aerobic activity among a sample of community-dwelling, older African Americans with a self-reported diagnosis of type 2 diabetes and other chronic conditions, such as hypertension and arthritis. Findings indicate that regardless of age, the number of chronic conditions was a significant influence in self-report of aerobic activity. Successful self-management of type 2 diabetes and other chronic conditions may promote physical activity among sedentary older African Americans with multiple chronic conditions. Furthermore, research that considers a life course epidemiological approach are needed to enhance our understanding about the cumulative effects of MCC on physical activity among sedentary, older African Americans with MCC.
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PMID:Self-Report of Aerobic Activity among Older African Americans with Multiple Chronic Conditions. 2947 77