Abstract: The present disclosure relates to, among other things, compounds and methods for treating neuropathic pain, ocular pain, ocular inflammation, and/or dry eye and methods of detecting mutations in specific G-protein coupled receptors, such as missense mutations, and determining the extent to which these mutations alter the pharmacological response of the G-protein coupled receptor.

Abstract: The present application provides methods for preparing soluble lipidated ligand agents comprising a ligand entity and a lipid entity, and in some embodiments, provides relevant parameters of each of these components, thereby enabling appropriate selection of components to assemble active agents for any given target of interest.

Abstract: The present disclosure relates to, among other things, compositions and methods for treating an inflammatory condition including, but not limited to, ocular inflammation, dry eye disease, and ocular neuropathic pain. One aspect of the present disclosure relates to a composition comprising (a) chemerin or a fragment or analog thereof and (b) a lipid entity linked to the chemerin or fragment or analog thereof.

Abstract: The present application provides methods for preparing soluble lipidated ligand agents comprising a ligand entity and a lipid entity, and in some embodiments, provides relevant parameters of each of these components, thereby enabling appropriate selection of components to assemble active agents for any given target of interest.

Abstract: The present disclosure relates to, among other things, compositions and methods for treating an inflammatory condition including, but not limited to, ocular inflammation, dry eye disease, and ocular neuropathic pain. One aspect of the present disclosure relates to a composition comprising (a) chemerin or a fragment or analog thereof and (b) a lipid entity linked to the chemerin or fragment or analog thereof.

Abstract: Disclosed are methods of treating autism spectrum disorder (ASD) by administering a therapeutically effective amount of an isoprenoid antibiotic. Also disclosed are methods of modulating (either upregulation or downregulation) hnRNP L and hnRNP L targets by administering a therapeutically effective amount of an isoprenoid antibiotic. Methods of screening compounds for use in treating autism spectrum disorder (ASD) are also described.

Abstract: Disclosed are methods of treating autism spectrum disorder (ASD) by administering a therapeutically effective amount of an isoprenoid antibiotic to subjects identified with a splicing defect in an ASD associated gene. The method of treating a subject with a neurological disease is carried out by identifying the subject comprising a splicing defect in an autism spectrum disorder (ASD)-associated gene, the target gene being characterized as having an hnRNP L binding site. The subject is treated by administering a spliceopathy rescue agent to repair the splicing defect. Also disclosed are methods of upregulating hnRNP L and hnRNP L targets by administering a therapeutically effective amount of an isoprenoid antibiotic. Methods of screening compounds for use in treating autism spectrum disorder (ASD) are also described.

Abstract: The present disclosure relates to, among other things, compounds and methods for treating neuropathic pain, ocular pain, ocular inflammation, and/or dry eye and methods of detecting mutations in specific G-protein coupled receptors, such as missense mutations, and determining the extent to which these mutations alter the pharmacological response of the G-protein coupled receptor.

Abstract: The present disclosure relates to, among other things, compounds and methods for treating neuropathic pain, ocular pain, ocular inflammation, and/or dry eye and methods of detecting mutations in specific G-protein coupled receptors, such as missense mutations, and determining the extent to which these mutations alter the pharmacological response of the G-protein coupled receptor.

Abstract: The present application provides methods for preparing soluble lipidated ligand agents comprising a ligand entity and a lipid entity, and in some embodiments, provides relevant parameters of each of these components, thereby enabling appropriate selection of components to assemble active agents for any given target of interest.

Abstract: The present application provides methods for preparing soluble lipidated ligand agents comprising a ligand entity and a lipid entity, and in some embodiments, provides relevant parameters of each of these components, thereby enabling appropriate selection of components to assemble active agents for any given target of interest.

Abstract: The present disclosure relates to, among other things, compositions and methods for treating an inflammatory condition including, but not limited to, ocular inflammation, dry eye disease, and ocular neuropathic pain. One aspect of the present disclosure relates to a composition comprising (a) chemerin or a fragment or analog thereof and (b) a lipid entity linked to the chemerin or fragment or analog thereof.

Abstract: The present disclosure relates to, among other things, compounds and methods for treating neuropathic pain, ocular pain, ocular inflammation, and/or dry eye and methods of detecting mutations in specific G-protein coupled receptors, such as missense mutations, and determining the extent to which these mutations alter the pharmacological response of the G-protein coupled receptor.

Abstract: Disclosed are methods of treating a muscle disease and improving normal muscle function by administering a therapeutically effective amount of an isoprenoid antibiotic. Also disclosed are methods of upregulating hnRNP L and hnRNP L targets by administering a therapeutically effective amount of an isoprenoid antibiotic. Methods of screening compounds for use in treating muscle disease and improving muscle function are also described.

Abstract: The present application provides methods for preparing soluble lipidated ligand agents comprising a ligand entity and a lipid entity, and in some embodiments, provides relevant parameters of each of these components, thereby enabling appropriate selection of components to assemble active agents for any given target of interest.

Abstract: Disclosed are methods of treating a muscle disease and improving normal muscle function by administering a therapeutically effective amount of an isoprenoid antibiotic. Also disclosed are methods of upregulating hnRNP L and hnRNP L targets by administering a therapeutically effective amount of an isoprenoid antibiotic. Methods of screening compounds for use in treating muscle disease and improving muscle function are also described.

Abstract: The present invention provides an alternative strategy for optimizing the signal to noise ratio of a given receptor. Specifically, the present invention provides receptor mutants having an increased signal to noise ratio. In one preferred embodiment, the present invention provides receptor mutants having a decreased level of basal activity. As part of this aspect, the present invention provides a mutant serotonin receptor and a mutant CCR-3 receptor, each having decreased basal activity. In another preferred embodiment, the present invention provides receptor mutants having an increased maximal level of ligand induced signaling. Such receptors optimize the signal to noise ratio of a receptor and provide, for example, for more sensitive screens for drug discovery.

Abstract: In general, the invention features methods that make use of animals expressing constitutively active G protein-coupled receptors for testing therapeutic efficacy and drug screening. Because these assays do not require animal breeding, they provide rapid assay results.

Abstract: The invention features a method for determining whether a candidate compound is a non-peptide agonist of a peptide hormone receptor. In this method, a candidate compound is exposed to a form of the peptide hormone receptor, or to a protein that interacts with a peptide hormone receptor, which has an enhanced ability to amplify the intrinsic activity of a non-peptide agonist. The second messenger signaling activity of the enhanced receptor is measured in the presence of the candidate compound, and compared to the second messenger signaling activity of the wildtype receptor measured in the absence of the candidate compound. A change in second messenger signaling activity indicates that the candidate compound is an agonist. An increase in second messenger signaling activity indicates that the compound is either a full or partial positive agonist; a decrease in second messenger signaling activity indicates that the compound is an inverse (also termed a ‘negative’) agonist.

Abstract: The invention features a method for determining whether a candidate compound is a non-peptide agonist of a peptide hormone receptor. In this method, a candidate compound is exposed to a form of the peptide hormone receptor which has an enhanced ability to amplify the intrinsic activity of a non-peptide agonist. The second messenger signaling activity of the enhanced receptor is measured in the presence of the candidate compound, and compared to the second messenger signaling activity of the enhanced receptor measured in the absence of the candidate compound. A change in second messenger signaling activity indicates that the candidate compound is an agonist. An increase in second messenger signaling activity indicates that the compound is either a full or partial positive agonist; a decrease in second messenger signaling activity indicates that the compound is an inverse (also termed a ‘negative’) agonist.