Abstract: This disclosure provides piperazine carbamates and compositions which may be modulators of MAGL and/or ABHD6 and their use as medicinal agents, processes for their preparation, and pharmaceutical compositions that include disclosed piperazine carbamates as at least one active agent. The disclosure also provides for method of treating a patient in need thereof, where the patient is suffering from indications such as pain, solid tumor cancer and/or obesity comprising administering a disclosed compound or composition.

Abstract: This disclosure provides compounds and compositions which may be modulators of MAGL and/or ABHD6 and their use as medicinal agents, processes for their preparation, and pharmaceutical compositions that include disclosed compounds as at least one active agent. The disclosure also provides for method of treating a patient in need thereof, where the patient is suffering from indications such as pain, solid tumor cancer and/or obesity comprising administering a disclosed compound or composition.

Abstract: Provided herein are carbamate compounds which may be useful in the treatment of for example, pain, solid tumors and/or obesity.

Abstract: A multidimensional profiling strategy that combines activity-based proteomics and metabolomics was used to determine that an active protein, which is a previously uncharacterized enzyme highly elevated in aggressive cancer cells, serves as a central node in an ether lipid signaling network that bridges platelet-activating factor and the lysophospholipids. Biochemical studies confirmed that the active protein regulates this pathway by hydrolyzing the metabolic intermediate 2-acetyl monoalkylglycerol. Inactivation of the active protein disrupted ether lipid metabolism in cancer cells and impaired cell migration and tumor growth in vivo.

Abstract: This disclosure provides compounds and compositions which may be modulators of MAGL and/or ABHD6 and their use as medicinal agents, processes for their preparation, and pharmaceutical compositions that include disclosed compounds as at least one active agent. The disclosure also provides for method of treating a patient in need thereof, where the patient is suffering from indications such as pain, solid tumor cancer and/or obesity comprising administering a disclosed compound or composition.

Abstract: This invention provides compounds that selectively inhibit monoacylglycerol lipase (MAGL). The invention also provides methods of using the MAGL selective inhibitors to stimulate 2-Arachidonoylglycerol (2-AG) mediated endocannabinoid signaling in vivo, and to treat conditions that are associated with or linked to endocannabinoid signaling. The invention additionally provides methods of treating cancer or inhibiting tumor growth by targeting MAGL with MAGL specific inhibitors. The invention further provides methods of screening for MAGL inhibitors with improved biochemical and pharmaceutical properties.

Abstract: A multidimensional profiling strategy that combines activity-based proteomics and metabolomics was used to determine that an active protein, which is a previously uncharacterized enzyme highly elevated in aggressive cancer cells, serves as a central node in an ether lipid signaling network that bridges platelet-activating factor and the lysophospholipids. Biochemical studies confirmed that the active protein regulates this pathway by hydrolyzing the metabolic intermediate 2-acetyl monoalkylglycerol. Inactivation of the active protein disrupted ether lipid metabolism in cancer cells and impaired cell migration and tumor growth in vivo.

Abstract: This invention provides compounds that selectively inhibit monoacylglycerol lipase (MAGL). The invention also provides methods of using the MAGL selective inhibitors to stimulate 2-Arachidonoylglycerol (2-AG) mediated endocannabinoid signaling in vivo, and to treat conditions that are associated with or linked to endocannabinoid signaling. The invention additionally provides methods of treating cancer or inhibiting tumor growth by targeting MAGL with MAGL specific inhibitors. The invention further provides methods of screening for MAGL inhibitors with improved biochemical and pharmaceutical properties.

Abstract: A multidimensional profiling strategy that combines activity-based proteomics and metabolomics was used to determine that an active protein, which is a previously uncharacterized enzyme highly elevated in aggressive cancer cells, serves as a central node in an ether lipid signaling network that bridges platelet-activating factor and the lysophospholipids. Biochemical studies confirmed that the active protein regulates this pathway by hydrolyzing the metabolic intermediate 2-acetyl monoalkylglycerol. Inactivation of the active protein disrupted ether lipid metabolism in cancer cells and impaired cell migration and tumor growth in vivo.

Abstract: The present invention is directed to FAAH crystals in complex with the inhibitor methoxyarachidonyl fluorophosphonate (MAFP) and to the use of these crystals to determine the three-dimensional structure of FAAH. This invention id further directed to the use of this structure for the modeling or determination of the structures of related proteins. This invention is further directed to the use of this structure in the pursuit of drug design to identify, characterize, or optimize agents which bind to the active site, substrate channels, product channels, or regulatory sites of FAAH, and to the evaluation of these agents to identify agents which may stimulate, inhibit, relocalize, stabilize, or destabilize FAAH and/or its activity. This invention is further directed to the use of this structure in the development of engineered FAAH variants which display altered solubility, catalytic profiles, or substrate specificity.

Abstract: The invention relates to an animal model for studying behavior related to fatty acid amide and hydrolysis of fatty acid amide. The invention provides transgenic animals in which the protein fatty acid amide hydrolase is not expressed, and methods of using such animals.

Abstract: The soporific activity of cis-9,10-octadecenoamide and other soporific fatty acid primary amides is neutralized by hydrolysis in the presence of fatty-acid amide hydrolase (FAAH). Hydrolysis of cis-9,10-octadecenoamide by FAAH leads to the formation of oleic acid, a compound without soporific activity. FAAH has be isolated and the gene encoding FAAH has been cloned, sequenced, and used to express recombinant FAAH. Inhibitors of FAAH are disclosed to block the hydrolase activity.

Abstract: Activity-based compositions for analyzing metalloproteases are disclosed, where the compositions include a chemical compound including a hydroxamate moiety and a benzophenone moiety. Methods for synthesizing these compounds are also disclosed, as well as methods of using them for determining the bioactivity of a compositions comprising active compounds toward a metalloproteases and for determining the potency of an inhibitor against a metalloprotease.

Abstract: The present invention provides methods for analyzing proteomes, as cells or lysates. The analysis is based on the use of probes that have specificity to the active form of proteins, particularly enzymes and receptors. The probes can be identified in different ways. In accordance with the present invention, a method is provided for generating and screening compound libraries that are used for the identification of lead molecules, and for the parallel identification of their biological targets. By appending specific functionalities and/or groups to one or more binding moieties, the reactive functionalities gain binding affinity and specificity for particular proteins and classes of proteins. Such libraries of candidate compounds, referred to herein as activity-based probes, or ABPs, are used to screen for one or more desired biological activities or target proteins.

Abstract: The soporific activity of cis-9,10-octadecenoamide and other soporific fatty acid primary amides is neutralized by hydrolysis in the presence of fatty-acid amide hydrolase (FAAH). Hydrolysis of cis-9,10-octadecenoamide by FAAH leads to the formation of oleic acid, a compound without soporific activity. FAAH has be isolated and the gene encoding FAAH has been cloned, sequenced, and used to express recombinant FAAH. Inhibitors of FAAH are disclosed to block the hydrolase activity.

Abstract: The soporific activity of cis-9,10-octadecenoamide and other soporific fatty acid primary amides is neutralized by hydrolysis in the presence of fatty-acid amide hydrolase (FAAH). Hydrolysis of cis-9,10-octadecenoamide by FAAH leads to the formation of oleic acid, a compound without soporific activity. FAAH has be isolated and the gene encoding FAAH has been cloned, sequenced, and used to express recombinant FAAH. Inhibitors of FAAH are disclosed to block the hydrolase activity.

Abstract: Methods and compositions are provided for evaluating cellular status related to neoplasia. Affinity based probes, particularly having fluorophosphonates as a reactive functionality, are employed that react with a family of enzymes having a common catalytic activity, particularly serine/threonine hydrolases. The probe(s) are combined with the cell components and resulting conjugates are characterized, where the profile of reaction indicates cellular status. A novel serine/threonine hydrolase enzyme is provided.

Abstract: The invention relates to an animal model for studying behavior related to fatty acid amide and hydrolysis of fatty acid amide. The invention provides transgenic animals in which the protein fatty acid amide hydrolase is not expressed, and methods of using such animals.

Abstract: The soporific activity of cis-9,10-octadecenoamide and other soporific fatty acid primary amides is neutralized by hydrolysis in the presence of fatty-acid amide hydrolase (FAAH). Hydrolysis of cis-9,10-octadecenoamide by FAAH leads to the formation of oleic acid, a compound without soporific activity. FAAH has be isolated and the gene encoding FAAH has been cloned, sequenced, and used to express recombinant FAAH. Inhibitors of FAAH are disclosed to block the hydrolase activity.

Abstract: The present invention provides methods for analyzing proteomes, as cells or lysates. The analysis is based on the use of probes that have specificity to the active form of proteins, particularly enzymes and receptors. The probes can be identified in different ways. In accordance with the present invention, a method is provided for generating and screening compound libraries that are used for the identification of lead molecules, and for the parallel identification of their biological targets. By appending specific functionalities and/or groups to one or more binding moieties, the reactive functionalities gain binding affinity and specificity for particular proteins and classes of proteins. Such libraries of candidate compounds, referred to herein as activity-based probes, or ABPs, are used to screen for one or more desired biological activities or target proteins.