Abstract: The present disclosure provides a crystal structure of aldehyde dehydrogenase (ALDH) with a modulator of ALDH bound thereto. The present disclosure provides a computer readable medium comprising atomic coordinates for an ALDH polypeptide and a modulator bound to a site within the polypeptide. A method is also provided. In general terms, the method comprises computationally identifying a compound that binds to an ALDH polypeptide, using the atomic coordinates.

Abstract: Methods of increasing blood flow in a mammalian brain blood vessel characterized by, or otherwise experiencing, decreased blood flow due to an ischemic or other hypoxic event, vasoconstriction or vasospasm following hemorrhagic stroke; due to chronic high blood pressure; and/or due to idiopathic causes are provided. The method for increasing blood flow in such a mammalian brain blood vessel includes administering to a patient in need thereof a therapeutically effective amount of an inhibitor of ? protein kinase C. In certain embodiments, the inhibitor can be chronically administered without causing desensitization of the patient to the inhibitor. Kits for increasing blood flow in a mammalian brain blood vessel characterized by, or otherwise experiencing, decreased blood flow due to an ischemic or other hypoxic event, vasoconstriction or vasospasm following hemorrhagic stroke; due to chronic high blood pressure; and/or due to idiopathic causes are provided.

Abstract: A method of reducing damage to cells and tissue caused by an ischemic or hypoxic event is disclosed. The method includes administering to the cell or tissue, either in vivo or ex vivo, ??RACK peptide. The peptide can be administered before, during or after the ischemic or hypoxic event.

Abstract: PKC V5 isozyme-specific peptides are described. The sequences and compositions comprising the sequences are useful for treating disease states associated with the PKC isozyme from which they are respectively derived. Methods of treatment, pharmaceutical formulations and methods of identifying compounds that mimic the activity of the peptides are also described.

Abstract: Peptides able to inhibit or activate the translocation or function of ?PKC are identified. Administration of the peptides for protection or enhancement of cell damage due to ischemia is described. Therapeutic methods to reduce damage to cells or to enhance damage to cells due to ischemia are also described, as well as methods for screening test compounds for ?PKC-selective agonists and antagonists.

Abstract: Methods of decreasing the extent of occlusion in the lumen of a mammalian blood vessel due to an ischemic or other hypoxic event are provided. In one form, a method includes administering to a patient in need thereof a pharmaceutically effective amount of an inhibitor of ? protein kinase C, either alone or in combination with a second therapeutic agent, and wherein the blood vessel is a blood vessel of the microvasculature. Additionally, methods of decreasing endothelial cell swelling in a mammalian blood vessel due to an ischemic or other hypoxic event are also provided. In one form, a method includes administering to a patient in need thereof a pharmaceutically effective amount of an inhibitor of ? protein kinase C, either alone or in combination with a second therapeutic agent.

Abstract: Methods of increasing blood flow in a mammalian brain blood vessel characterized by, or otherwise experiencing, decreased blood flow due to an ischemic or other hypoxic event, vasoconstriction or vasospasm following hemorrhagic stroke; due to chronic high blood pressure; and/or due to idiopathic causes are provided. The method for increasing blood flow in such a mammalian brain blood vessel includes administering to a patient in need thereof a therapeutically effective amount of an inhibitor of ? protein kinase C. In certain embodiments, the inhibitor can be chronically administered without causing desensitization of the patient to the inhibitor. Kits for increasing blood flow in a mammalian brain blood vessel characterized by, or otherwise experiencing, decreased blood flow due to an ischemic or other hypoxic event, vasoconstriction or vasospasm following hemorrhagic stroke; due to chronic high blood pressure; and/or due to idiopathic causes are provided.

Abstract: The present invention provides screening methods for identifying agents that modulate the activity of mitochondrial aldehyde dehydrogenase-2 (AldDH2), as well as agents identified by the screening methods. The present invention further provides methods of reducing ischemic tissue damage or free-radical induced damage in an organ, the methods generally involving contacting the organ with an agent that increases AldDH2 levels and/or activity. The present invention further provides methods of treating solid tumors, the methods generally involving administering an agent that decreases AldDH2 levels and/or activity.

Abstract: A method of reducing damage to cells and tissue caused by an ischemic or hypoxic event is disclosed. The method includes administering to the cell or tissue, either in vivo or ex vivo, ??RACK peptide. The peptide can be administered before, during or after the ischemic or hypoxic event.

Abstract: Peptide sequences derived from the V5 domain of isozymes of protein kinase C for use in pain management are described. Also described are compositions comprising the peptides for treating pain and/or inducing analgesia. Methods of pain treatment and methods of identifying compounds that mimic the activity of the peptides are also described.

Abstract: A method of changing or otherwise converting the biological activity of a PKC peptide agonist to a peptide antagonist is described. The method involves substituting one or more amino acid residues so as to effect a change in charge in the peptide and/or to otherwise make the sequence similar to a sequence derived from the PKC binding site on the RACK protein for the respective PKC enzyme. Methods of inhibiting the activity of a PKC enzyme, and various peptide antagonists of ?PKC are also disclosed.

Abstract: The present invention provides compounds that function as modulators of mitochondrial aldehyde dehydrogenase-2 (ALDH2) activity; and pharmaceutical compositions comprising the compounds. The present invention provides therapeutic methods involving administering a subject compound, or a subject pharmaceutical composition. The present invention further provides assays for identifying agonists of ALDH2.

Abstract: PKC V5 isozyme-specific peptides are described. The sequences and compositions comprising the sequences are useful for treating disease states associated with the PKC isozyme from which they are respectively derived. Methods of treatment, pharmaceutical formulations and methods of identifying compounds that mimic the activity of the peptides are also described.

Abstract: Peptides able to inhibit or activate the translocation or function of ?PKC are identified. Administration of the peptides for protection or enhancement of cell damage due to ischemia is described. Therapeutic methods to reduce damage to cells or to enhance damage to cells due to ischemia are also described, as well as methods for screening test compounds for ?PKC-selective agonists and antagonists.

Abstract: Peptide sequences derived from the V5 domain of isozymes of protein kinase C for use in pain management are described. Also described are compositions comprising the peptides for treating pain and/or inducing analgesia. Methods of pain treatment and methods of identifying compounds that mimic the activity of the peptides are also described.

Abstract: A method for managing withdrawal from an addictive substance is described. The method involves administering one or more peptides having specific activity for the ? and/or ? isozyme of protein kinase C (PKC). The peptide(s) can be administered prior to, concurrent with, or subsequent to administration of the addictive substance. Also described is a kit having at least one container containing a peptide having isozyme-specific activity for ?PKC or ?PKC and instructions for use.

Abstract: PKC V5 isozyme-specific peptides are described. The sequences and compositions comprising the sequences are useful for treating disease states associated with the PKC isozyme from which they are respectively derived. Methods of treatment, pharmaceutical formulations and methods of identifying compounds that mimic the activity of the peptides are also described.

Abstract: PKC V5 isozyme-specific peptides are described. The sequences and compositions comprising the sequences are useful for treating diseases states associated with the PKC isozyme from which they are respectively derived. Methods of treatment, pharmaceutical formulations and methods of identifying compounds that mimic the activity of the peptides are also described.

Abstract: The present invention provides screening methods for identifying agents that modulate the activity of mitochondrial aldehyde dehydrogenase-2 (AldDH2), as well as agents identified by the screening methods. The present invention further provides methods of reducing ischemic tissue damage or free-radical induced damage in an organ, the methods generally involving contacting the organ with an agent that increases AldDH2 levels and/or activity. The present invention further provides methods of treating solid tumors, the methods generally involving administering an agent that decreases AldDH2 levels and/or activity.

Abstract: Methods are described for slowing or inhibiting the progression of heart failure in a mammalian subject suffering from chronic hypertension. The methods involve administering an ?PKC, ?1PKC, or ?IIPKC peptide inhibitor, examples of which are provided.