摘要:
Methods for determining an optimal binding motif for a binding compound are provided in which the binding compound is contacted with an oriented degenerate cyclic peptide library (ODCPL) under conditions which allow for interaction between the binding compound and the ODCPL such that a complex is formed between the binding compound and a subpopulation of library members capable of interacting with the binding compound. The subpopulation of library members capable of interacting with the binding compound is then separated from library members that are incapable of interacting with the binding compound. The subpopulation of library members capable of interacting with the binding compound is linearized to form a subpopulation of linearized library members. The amino acid sequence of the subpopulation of linearized library members is determined and an amino acid sequence motif is then determined for an interaction site of the binding compound, based upon the relative abundance of different amino acid residues at each degenerate position within the linearized library members. Oriented degenerate cyclic peptide libraries, and methods for purifying cyclic peptides from linear peptides, are also provided.
摘要:
The invention relates to inhibition of Par- 1b kinase activity for treating disorders including diabetes and obesity. The invention also relates to screening for compounds or compositions that inhibit the kinase activity of Par- 1b protein, which compounds and compositions are useful in the treatment of diabetes and obesity, as well as preparing compounds for treatment of diabetes and obesity.
摘要:
The invention provides methods for modulating type IIβ phosphoinisitide phosphate kinase (PIPKIIβ) activity for treating PIPKIIβ-associated disorders. The invention also provides methods of identifying candidate agents for treating PIPKIIβ-associated disorders.
摘要:
Provided herein are methods for treating cancer that is resistant to treatment with an anti- ErbB therapeutic agent and which is associated with an activating MET gene mutation or a MET gene amplification. The methods involve administering to a subject a combination of an anti- ErbB therapeutic and an anti-MET therapeutic. Also provided are methods for reducing ErbB mediated signaling or PI3 kinase mediated signaling in a cancer cell.
摘要:
The invention provides pharmaceutical compositions, kits, and methods of treating cancer, diabetes, obesity, autoimmune disease, and benign prostatic hyperplasia using compounds that selectively inhibit pyruvate kinase M2 and an assay measuring chemical modulation of pyruvate kinase activity.