摘要:
Insulin-incretin conjugates comprising a peptide having agonist activity at the glucagon-like 1 (GLP-1) receptor, the glucagon (GCG) receptor, and/or the gastric inhibitory protein (GIP) receptor conjugated to an insulin molecule having agonist activity at the insulin receptor and use of the conjugates for treatment of metabolic diseases, for example, Type 2 diabetes, are described.
摘要:
Insulin conjugates comprising an insulin analog molecule covalently attached to at least one bi-dentate linker having two arms, each arm independently attached to a ligand comprising a saccharide and wherein the saccharide for at least one ligand of the linker is fucose are disclosed. The insulin conjugates display a pharmacokinetic (PK) and/or pharmacodynamic (PD) profile that is responsive to the systemic concentrations of a saccharide such as glucose or alpha-methylmannose even when administered to a subject in need thereof in the absence of an exogenous multivalent saccharide-binding molecule such as Con A.
摘要:
The present invention relates to methods for isolating polypepitdes from cells. The methods may be used to isolate denatured polypeptides or native polypeptides. In one embodiment the methods may be used to isolated polypeptide from cytosolic and nuclear compartments of eukaryotic cells. In one embodiment the methods may be used to isolate polypeptides from bacterial cells.
摘要:
A compound having the structure or a pharmaceutically acceptable salt thereof, wherein R6 is hydrogen, —OH, —C1-6alkyl, —OC1-6alkyl, aryl, or halogen, or together with R7, forms an oxo group, or together with R7 and the atom to which they are attached, form a 5-7-membered carbocycle ring or a 5-7-membered heterocyclic ring having 1, 2, or 3 heteroatoms, wherein alkyl and aryl are unsubstituted or independently mono-, di-, or tri-substituted with R14; R7 is hydrogen, C1-6alkyl, —CF3, aryl, —O-aryl, —O—C1-6alkyl, —C(O)OC1-6alkyl, —C(R15R16)OH, a 5-7-membered heteroaryl having 1, 2, 3 or 4 nitrogen atoms, or halogen, or together with R6, forms an oxo group, or together with R6 and the atom to which they are attached, form a 5-7-membered carbocycle ring or a 5-7-membered heterocyclic ring having 1, 2, or 3 heteroatoms wherein alkyl, aryl and heteroaryl are unsubstituted or independently mono-, di- or tri-substituted with R14; R12 is hydrogen, C1-6alkyl, or —(CH2)1-2OH, or together with R13 and the nitrogen atom to which they are attached, form a 4- to 7-membered heterocyclic ring containing one nitrogen atom and 0 or 1 oxygen atoms, wherein said ring is unsubstituted or independently mono-, di- or tri-substituted with halogen or —C1-6alkyl; R13 is —C1-6alkyl or —(CH2)1-2OH, or together with R12 and the nitrogen atom to which they are attached, form a 4- to 7-membered heterocyclic ring containing one nitrogen atom and 0 or 1 oxygen atoms, wherein said ring is unsubstituted or independently mono-, di- or tri-substituted with halogen or —C1-6alkyl.
摘要:
Pharmaceutical compositions containing a cocktail of inhibitors of central stress nuclei are provided. The pharmaceutical compositions are useful for the prevention and treatment of a variety of conditions in mammals including humans, including anxiety and mood disorders such as depression.
摘要:
A compound having the structure: useful for treating hypertension, Pulmonary Arterial Hypertension (PAH), congestive heart failure, conditions resulting from excessive water retention, cardiovascular disease, diabetes, oxidative stress, endothelial dysfunction, cirrhosis, pre-eclampsia, osteoporosis or nephropathy.
摘要:
A compound having the structure useful for treating hypertension, Pulmonary Arterial Hypertension (PAH), congestive heart failure, conditions resulting from excessive water retention, cardiovascular disease, diabetes, oxidative stress, endothelial dysfunction, cirrhosis, pre-eclampsia, osteoporosis or nephropathy.
摘要:
An tri-axis accelerometer is disclosed. The tri-axis accelerometer includes a mass, a first group of capacitance, a third group of capacitance being neighbor to the first group of capacitance. The mass defines an upper surface, a lower surface parallel to the upper surface and a side wall connecting the upper surface and the lower surface. The first group of capacitance includes a first movable electrode and the third group of capacitance includes a third movable electrode. The first movable electrode is perpendicular to the third movable electrode.
摘要:
A compound having the structure wherein X is selected from the group consisting of: a bond, —NHCH2(CH2)nCH2OC(O)—, —CH2NHC(O)CH2NHC(O)—, —CH2OC(O)—, —OCH(CH3)OC(O)—, —OCH2OC(O)—, —O—, —NR1—, —CR1R3—, —(CH2)p—, —(CH2)qNR1C(O)—, —CHR5NR2C(O)—, —(CH2)qC(O)—, —(CH2)qC(O)—, —(CH2)qC(O)NR1—, or a pharmaceutically acceptable salt thereof, and methods of using the compounds for treating, hypertension.
摘要:
Novel heterocyclo compounds useful as inhibitors of potassium channel function (especially inhibitors of the Kv1 subfamily of voltage gated K+ channels, especially inhibitors Kv1.5 which has been linked to the ultra-rapidly activating delayed rectifier K+ current IKur), methods of using such compounds in the prevention and treatment of arrhythmia and IKur-associated conditions, and pharmaceutical compositions containing such compounds.