Abstract:
The present invention relates to a method of treating a disorder mediated by soluble adenylyl cyclase in a subject. The method involves administering to a subject an effective amount of a compound disclosed herein that modulates soluble adenylyl cyclase, under conditions effective to treat the disorder mediated by soluble adenylyl cyclase. The present invention also relates to a method of treating a disorder mediated by soluble adenylyl cyclase in a subject, where the disorder is selected from the group consisting of: learning or memory disorders, malaria, fungal infection, spinal cord injury, Alzheimer's disease, amyotrophic lateral sclerosis, and peripheral neuropathy. The method involves modulating soluble adenylyl cyclase in the subject. Another aspect of the present invention relates to a method of modulating soluble adenylyl cyclase. The method involves contacting eukaryotic cells with a compound that modulates soluble adenylyl cyclase, under conditions effective to modulate soluble adenylyl cyclase.
Abstract:
The present invention relates to a method of preventing or treating a disease caused by infection by a eukaryotic pathogen, wherein the method comprises administering an effective amount of a modulator of a eukaryotic pathogen's adenylyl cyclase. The invention also provides pharmaceutical compositions useful for preventing or treating a disease, with the compositions containing a therapeutically effective amount of a modulator of a eukaryotic pathogen's adenylyl cyclase. The invention also provides screening methods for identifying selective modulators of a eukaryotic pathogen's adenylyl cyclase that do not substantially modulate an adenylyl cyclase of the subject. The invention also provides methods for culturing eukaryotic pathogens and methods for inducing the pathogenic state in vitro.
Abstract:
The present invention relates to a method of preventing or treating a disease caused by bacterial infection by administering an effective amount of a modulator of bacterial adenylyl cyclase. The invention also provides pharmaceutical compositions useful for preventing or treating a disease, with the compositions containing a therapeutically effective amount of a modulator of bacterial adenylyl cyclase. The invention also provides screening methods for identifying selective modulators of bacterial adenylyl cyclase that do not substantially modulate adenylyl cyclase of the subject. The invention also provides methods for culturing bacterial pathogens and methods for inducing the pathogenic state in vitro.
Abstract:
A pharmaceutical composition which comprises the c-kit ligand (KL) purified by applicants or produced by applicants' recombinant methods in combination with other hematopoietic factors and a pharmaceutically acceptable carrier is provided as well as methods of treating patients which comprise administering to the patient the pharmaceutical composition of this invention. This invention provides combination therapies using c-kit ligand (KL) and a purified c-kit ligand (KL) polypeptide, or a soluble fragment thereof and other hematopoietic factors. It also provides methods and compositions for ex-vivo use of KL alone or in combination therapy. A mutated KL antagonist is also described. Such an antagonist may also be a small molecule. Antisense nucleic acids to KL as therapeutics are also described. Lastly, compositions and methods are described that take advantage of the role of KL in germ cells, mast cells and melanocytes.
Abstract:
A pharmaceutical composition which comprises the c-kit ligand (KL) purified by applicants or produced by applicants' recombinant methods in combination with other hematopoietic factors and a pharmaceutically acceptable carrier is provided as well as methods of treating patients which comprise administering to the patient the pharmaceutical composition of this invention. This invention provides combination therapies using c-kit ligand (KL) and a purified c-kit ligand (KL) polypeptide, or a soluble fragment thereof and other hematopoietic factors. It also provides methods and compositions for ex-vivo use of KL alone or in combination therapy. A mutated KL antagonist is also described. Such an antagonist may also be a small molecule. Antisense nucleic acids to KL as therapeutics are also described. Lastly, compositions and methods are described that take advantage of the role of KL in germ cells, mast cells and melanocytes.
Abstract:
The present invention relates to retinol dehydratase, the enzyme which synthesizes the retro-retinoid anhydroretinol in the Spodoptera frugiperda insect cell line Sf-21, as well as the DNA molecule encoding that enzyme. The DNA molecule can be incorporated in a DNA expression system and a host for recombinant production of anhydroretinol dehydratase. The isolated retinol dehydratase protein or polypeptide of the present invention can be combined with a pharmaceutically-acceptable carrier or used alone for administration to mammals, particularly humans, for preventing cell growth and/or uncontrolled cell growth in cells which are growth dependent on retinol and/or 14 hydroxy-4, 14-retro-retinol.
Abstract:
For the first time, certain retinoids with a side chain terminal CH.sub.2 OH group or ester or ether thereof or aldehyde rather than a side chain terminal COOH group and substitution at the 4-position have been indicated to bind to nuclear receptors and to be biologically active in inducing cell differentiation of normal and tumor cells. These compounds activate gene expression through binding to nuclear receptor proteins. These compounds induce differentiation in normal and cancer cells and are useful for treating leukemias, and lymphomas, squamous cell carcinomas, deep (cystic) acne, psoriasis and photodamaged or aging skin. These compounds have stability and in vitro half-life advantages over and solubility differences from all-trans-retinoic acid and activity advantages over 13-cis retinoic acid.
Abstract:
Soluble adenylyl cyclase (sAC) is implicated in proliferation of keratinocytes. Inhibitors of sAC are useful for the treatment and/or prevention of psoriasis and other hyperproliferative skin disorders. Assays to identify such compounds are also described.
Abstract:
The invention provides a method for diagnosing a melanocytic proliferation in a subject comprising staining a sample of lesional melanocytes with an antibody against soluble adenylyl cyclase (sAC) and interpreting the sAC staining pattern, which is associated with a diagnosis of a melanocytic proliferation. The sAC staining pattern, which is complex, is discriminatory and distinctive according to the nature of the melanocytic proliferation. The sAC staining pattern comprises one or more of dot-like Golgi staining, broad granular Golgi staining, diffuse cytoplasmic staining, nucleolar staining, incomplete granular nuclear staining, and pan-nuclear staining. The method of the invention is particularly useful in confirming or disaffirming a diagnosis reached through conventional histologic examination of a sample. Additionally, the invention provides a kit for use in interpreting melanocytic proliferations.
Abstract:
Soluble adenylyl cyclase (sAC) is implicated in proliferation of keratinocytes. Inhibitors of sAC are useful for the treatment and/or prevention of psoriasis and other hyperproliferative skin disorders. Assays to identify such compounds are also described.