Patent ID: 8217025
Filing Date: 2012-07-10
Classification: A61K,A61P,G01N

Abstract:
1. A method to identify a compound with a potential to treat or ameliorate a metabolic disorder in a mammal, comprising selecting a compound that (i) does not activate one, two or three of PPAR-α, PPAR-γ and PPAR-δ in human or mammalian cells in vitro by more than about 30% when compared to suitable negative control human or mammalian cells in vitro; (ii) inhibits or decreases the transcriptional activity or level of NF-κB by about 20-80% in human or mammalian cells in vitro when compared to suitable negative control human or mammalian cells in vitro; (iii) when compared to a suitable negative control or normal control, (a) decreases the degree of hyperglycemia, (b) slows the progression of hyperglycemia, (c) delays the onset of hyperglycemia, (d) decreases the rate of macular degeneration, (e) delays the onset of macular degeneration, (f) decreases the occurrence or incidence of vascular ulcers, (g) decreases the severity of vascular ulcers, (h) increases insulin sensitivity, (i) decreases glucose intolerance, (j) slows the progression or rate of loss of pancreatic β-islet cell numbers or their capacity to secrete insulin, (k) increases pancreatic β-islet cell numbers or their capacity to secrete insulin, (l) slows the rate of weight increase in db/db mice or mice with diet induced obesity, (m) decreases elevated levels of triglycerides, (n) decreases elevated levels total blood or serum cholesterol, (o) decreases normal or elevated levels of LDL, VLDL, apoB-100 or apoB-48 in blood or serum, (p) increases normal or low levels of HDL or apoA1 in blood or serum, (q) decreases or normalizes an elevated level of a phase reactive protein, optionally C reactive protein or fibrinogen in blood or serum, (r) decreases or normalizes hemoglobin A (iv) optionally, does not activate one or more of a glucocorticoid receptor, an androgen receptor an estrogen receptor-α, estrogen receptor-β or a biologically active variant of any of these biomolecules in human or mammalian cells in vitro by more than about 30% when compared to suitable negative control human or mammalian cells in vitro; and (v) optionally inhibits the level or activity of phosphoenolpyruvate carboxykinase (PEPCK) or a 11β-hydroxysteroid dehydrogenase (11β-HSD), optionally 11β-HSD type 1 or 11β-HSD type 2 or the level of a mRNA that encodes PEPCK or a 11β-HSD, in hepatocytes or liver-derived cells in vitro or in liver cells or tissue obtained from liver cells or tissue in vivo; wherein the compound with a potential to treat or ameliorate the metabolic disorder in a mammal is identified and optionally recorded as such in a written or a readable electronic medium.