Abstract: Methods of treating or preventing diseases caused by viral infections via the administration of pyronaridine, quinacrine, and/or tilorone are described. The viral infections can be caused by viruses such as Marburg virus (MARV), Chikungunya virus (CHIKV), norovirus, Middle East Respiratory Syndrome coronavirus (MERS-CoV), and Nipah virus.

Abstract: The identification of new acetylcholinesterase (AChE) inhibitors is described. For example, tilorone was newly identified as an AChE inhibitor by use of a machine learning model followed by in vitro screening. The new AChE inhibitors can selectively inhibit AChE compared to butyrylcholinesterase (BuChE). Methods of inhibiting AChE and of treating or preventing diseases, disorders, and conditions treatable or preventable by AChE inhibition are also described. For example, methods of treating and/or preventing certain dermatological conditions and organophosphorous or nerve agent poisoning are described.

Abstract: Methods of treating or preventing diseases caused by viral infections via the administration of pyronaridine, quinacrine, and/or tilorone are described. The viral infections can be caused by viruses such as Marburg virus (MARV), Chikungunya virus (CHIKV), norovirus, Middle East Respiratory Syndrome coronavirus (MERS-CoV), and Nipah virus.

Abstract: Isoxazole-3-carboxamide derivatives and their use in treating viral infections and diseases, such as diseases caused by viruses of the Picornaviridae family of viruses (e.g., rhinoviruses, enteroviruses, and coxsackieviruses) is described. The derivatives have good efficacy against a range of viruses, including pleconaril-resistant viral strains, and have low induction of cytochrome P4503A4 (CYP3A4).

Abstract: Methods of modulating the interaction between ?-amyloid and ?7-nAChR are provided. Aspects of the methods include administering to the subject an effective amount of a naphthalene derivative active agent. Compositions and kits for practicing the subject methods are also provided. The methods, compositions and kits find use in treating a variety of applications, such as treating a subject for a neurodegenerative disease, e.g., Alzheimer's disease.

Abstract: The invention provides compounds of formula I: and salts thereof wherein R1-R5 have any of the meanings described in the specification. The compounds are useful for treating bacterial infections (e.g. tuberculosis).

Abstract: The invention provides compounds of formula (I): and salts thereof wherein R1-R5 have any of the meanings described in the specification. The compounds are useful for treating bacterial infections (e.g. tuberculosis).

Abstract: The present disclosure relates to compositions and methods for treating Sanfilippo syndrome (also known as Sanfilippo disease type D, Sanfilippo D, mucopolysaccharidosis type IIID, MPS IIID). The method can entail injecting to the spinal fluid of a MPS IIID patient an effective amount of a composition comprising a recombinant human acetylglucosamine-6-sulfatase (GNS) protein comprising the amino acid sequence of SEQ ID NO: 1 or an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 1 and having the enzymatic activity of the human GNS protein. The composition can be provided in an artificial cerebrospinal fluid. About 1 mg to about 100 mg of the recombinant polypeptide may be administered to the patient once every 2 weeks to 6 months.

Abstract: New antimicrobials targeting L,D-transpeptidases, non-classical cysteine peptidases, have been developed and their unique chemical structures identified. Carbapenems and penems of the present invention are unique among ?-lactams as they acylate and inhibit L,D-transpeptidases, which likely results in their superior antimicrobial potency. These new antimicrobial agents can be used alone, or in combination with other classic antimicrobial agents that target D,D transpeptidases, when treating bacterial infections.

Abstract: The invention provides compounds of formula (I): and salts thereof wherein R1-R5 have any of the meanings described in the specification. The compounds are useful for treating bacterial infections (e.g. tuberculosis).

Abstract: New antimicrobials targeting L,D-transpeptidases, non-classical cysteine peptidases, have been developed and their unique chemical structures identified. Carbapenems and penems of the present invention are unique among ?-lactams as they acylate and inhibit L,D-transpeptidases, which likely results in their superior antimicrobial potency. These new antimicrobial agents can be used alone, or in combination with other classic antimicrobial agents that target D,D transpeptidases, when treating bacterial infections.

Abstract: The present disclosure relates to compositions and methods for treating Sanfilippo syndrome (also known as Sanfilippo disease type D, Sanfilippo D, mucopolysaccharidosis type IIID, MPS IIID). The method can entail injecting to the spinal fluid of a MPS IIID patient an effective amount of a composition comprising a recombinant human acetylglucosamine-6-sulfatase (GNS) protein comprising the amino acid sequence of SEQ ID NO: 1 or an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 1 and having the enzymatic activity of the human GNS protein. The composition can be provided in an artificial cerebrospinal fluid. About 1 mg to about 100 mg of the recombinant polypeptide may be administered to the patient once every 2 weeks to 6 months.

Abstract: The present invention discloses methods of modulating the activity of Group I mGluRs using a defined class of benzamide compounds. In one embodiment, methods of modulating the activity of mGluR1 are provided. In another embodiment, methods of modulating the activity of mGluR5 are provided. In still another embodiment, methods of simultaneously modulating the activities of both mGluR1 and mGluR5 are provided. The present invention also provides methods of treating diseases or disorders which are mediated in full or in part by Group I mGluRs using one or more compounds belonging to the defined class of benzamide compounds. The present invention further provides methods of preventing diseases or disorders which are mediated in full or in part by Group I mGluRs using one or more compounds belonging to the defined class of compounds.

Abstract: A system is provided for the prediction of human drug metabolism and toxicity of novel compounds. The system enables the visualization of pre-clinical and clinical high-throughput data in the context of a complete biological organism. Substructure and similarity structure searches can be performed using the underlying databases of xenobiotics, active ligands, and endobiotics. The system also has an analytical component for the parsing, integration, and network analysis of genomics, proteomics, and metabolomics high-throughput data. From this information, the system further generates networks around proteins, genes and compounds to assess toxicity and drug-drug interactions.

Abstract: A system is provided for the prediction of human drug metabolism and toxicity of novel compounds. The system enables the visualization of pre-clinical and clinical high-throughput data in the context of a complete biological organism. Substructure and similarity structure searches can be performed using the underlying databases of xenobiotics, active ligands, and endobiotics. The system also has an analytical component for the parsing, integration, and network analysis of genomics, proteomics, and metabolomics high-throughput data. From this information, the system further generates networks around proteins, genes and compounds to assess toxicity and drug-drug interactions.

Abstract: The present invention discloses methods of modulating the activity of Group I mGluRs using a defined class of benzamide compounds. In one embodiment, methods of modulating the activity of mGluR1 are provided. In another embodiment, methods of modulating the activity of mGluR5 are provided. In still another embodiment, methods of simultaneously modulating the activities of both mGluR1 and mGluR5 are provided. The present invention also provides methods of treating diseases or disorders which are mediated in full or in part by Group I mGluRs using one or more compounds belonging to the defined class of benzamide compounds. The present invention further provides methods of preventing diseases or disorders which are mediated in full or in part by Group I mGluRs using one or more compounds belonging to the defined class of compounds.

Abstract: A system is provided for the prediction of human drug metabolism and toxicity of novel compounds. The system enables the visualization of pre-clinical and clinical high-throughput data in the context of a complete biological organism. Substructure and similarity structure searches can be performed using the underlying databases of xenobiotics, active ligands, and endobiotics. The system also has an analytical component for the parsing, integration, and network analysis of genomics, proteomics, and metabolomics high-throughput data. From this information, the system further generates networks around proteins, genes and compounds to assess toxicity and drug-drug interactions.

Abstract: The present invention relates to novel screening methods which enable the selection of neurokinin-1 (NK-1) receptor antagonist compounds which do not possess significant inhibitory potency towards cytochrome P450 enzymes, in particular, CYP2D6. The present invention also relates to a method of generating a pharmacophore model for the CYP2D6 inhibitory activity of NK-1 receptor antagonist compounds; to methods for the discovery of molecules that are potential NK-1 receptor antagonist compounds which do not possess significant inhibitory potency towards the CYP2D6 enzyme; to methods of modeling the features of the CYP2D6 pharmacophore useful in selecting NK-1 receptor antagonist molecules which do not possess significant potency towards CYP2D6.

Abstract: A method and device for the automated large scale preparation for testing of drug-drug interactions, particularly with determination of IC50 and Ki, as a screening tool enhancement for determining viability of large numbers of compounds as drug candidates. Small samples of specific probe substrates and new compound inhibitors are automatically dispensed en masse into multi-welled reaction plates which are prefilled with thawed human microsomes, buffer and cofactor. The reaction plates are incubated and the reaction products are tested within degradation time limits, for initial biological determinations of relevant interaction effects of the compounds.

Abstract: A method and device for the automated large scale preparation for testing of drug-drug interactions, particularly with determination of IC50 and Ki, as a screening tool enhancement for determining viability of large numbers of compounds as drug candidates. Small samples of specific probe substrates and new compound inhibitors are automatically dispensed en masse into multi-welled reaction plates which are prefilled with thawed human microsomes, buffer and cofactor. The reaction plates are incubated and the reaction products are tested within degradation time limits, for initial biological determinations of relevant interaction effects of the compounds.