Pharmacy and Pharmaceutical Sciences Commons^™

High-Activity Mutants Of Butyrylcholinesterase For Cocaine Hydrolysis And Method Of Generating The Same, Chang-Guo Zhan, Hoon Cho, Hsin-Hsiung Tai

Pharmaceutical Sciences Faculty Patents

A novel computational method and generation of mutant butyrylcholinesterase for cocaine hydrolysis is provided. The method includes molecular modeling a possible BChE mutant and conducting molecular dynamics simulations and hybrid quantum mechanical/molecular mechanical calculations thereby providing a screening method of possible BChE mutants by predicting which mutant will lead to a more stable transition state for a rate determining step. Site-directed mutagenesis, protein expression, and protein activity is conducted for mutants determined computationally as being good candidates for possible BChE mutants, i.e., ones predicted to have higher catalytic efficiency as compared with wild-type BChE. In addition, mutants A199S/A328W/Y332G, A199S/F227A/A328W/Y332G, A199S/S287G/A328W/Y332G, …

Methods And Compositions For Optimizing Blood And Tissue Stability Of Camptothecin And Other Albumin-Binding Therapeutic Compounds, Thomas G. Burke, Daniel C. Carter

Pharmaceutical Sciences Faculty Patents

The present invention provides methods and formulations for optimizing the anti-cancer and anti-HIV activities of a camptothecin drug, including camptothecin and its related analogs including 9-aminocamptothecin and 9-nitrocamptothecin. The invention involves methodologies and formulations that limit human serum albumin-mediated reduction of the anti-cancer and anti-HIV effects of the camptothecins, and the methods and formulations provide combination therapies in which binding of the camptothecin agent to human serum albumin can be modulated by the administration of a competing agent that also binds human serum albumin. Reduced camptothecin drug binding to human serum albumin can result in elevated camptothecin free drug levels …

Use Of Parthenolide Derivatives As Antileukemic And Cytotoxic Agents, Peter A. Crooks, Craig T. Jordan, Xiaochen Wei

Pharmaceutical Sciences Faculty Patents

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Methods To Impair Hematologic Cancer Progenitor Cells And Compounds Related Thereto, Craig Jordan

Pharmaceutical Sciences Faculty Patents

Primitive or progenitor hematologic cancer cells have been implicated in the early stages and development of leukemia and malignant lymphoproliferative disorders, including acute myelogenous leukemia (AML), chronic myelogenous leukemia (CML) and chronic lymphoid leukemia (CLL). Interleukin-3 receptor alpha chain (IL-3Rα or CD123) is strongly expressed on progenitor hematologic cancer cells, but is virtually undetectable on normal bone marrow cells. The present invention provides methods of impairing progenitor hematologic cancer (e.g., leukemia and lymphomic) cells by selectively targeting cells expressing CD123. These methods are useful in the detection and treatment of leukemias and malignant lymphoproliferative disorders. Also provided are compounds useful …

Epoxyketone-Based Immunoproteasome Inhibitors, Kyung Bo Kim, Yik Khuan Ho

Pharmaceutical Sciences Faculty Patents

An efficient new route for the preparation of dihydroeponemycin, an active eponemycin derivative, is provided, which includes the synthesis of the intermediate compound, a hydroxymethyl-substituted enone. In addition, a method is provided for synthesizing inhibitors, which includes PI′-modified analogues. These analogues selectively bind to a major immunoproteasome catalytic subunit LMP2 and inactivate its proteolytic activity in a method of treating diseases, including myeloma and other cancers, Huntington's disease and Alzheimer's disease.

Compositions Comprising Human Immunodeficiency Virus Tat Adsorbed To The Surface Of Anionic Nanoparticles, Russell J. Mumper, Jerold Woodward, Zhengrong Cui, Avindra Nath

Pharmaceutical Sciences Faculty Patents

Non-denatured, recombinant human immunodeficiency virus (HIV) Tat that is free of bacterial RNA and endotoxin is employed in an anti-HIV vaccine. A process of producing the recombinant Tat protein includes steps for removing bacterial RNA from the recombinant Tat and for removing endotoxin from the recombinant Tat protein. A Tat-adsorbed nanoparticle formulation and method of making the same. A method of vaccinating against and/or treating HIV infection comprises administering to a subject in need of such vaccination or treatment an immune-response inducing effective amount of the recombinant Tat protein.

Method And System For In Situ Spectroscopic Evaulation Of An Object, Robert A. Lodder

Pharmaceutical Sciences Faculty Patents

A method and system for spectroscopically determining surface and product characteristics is employed for rapid detection of product characteristics and/or the presence or absence of suspected analytes, and the concentration of the analyte. The method and system uses a signal wide band detector that does not require focusing optics in many environments. It can be used for cleaning validation of pharmaceutical products and process equipment.

Genes Encoding Several Poly (Adp-Ribose) Glycohydrolase (Parg) Enzymes, The Proteins And Fragments Thereof, And Antibodies Immunoreactive Therewith, Myron Jacobson, Elaine L. Jacobson, Jean-Christoph Amé, Winston Lin

Pharmaceutical Sciences Faculty Patents

The isolation and characterization of cDNAs encoding poly(ADP-ribose) glycohydrolase (PARG) enzymes and the amino acid sequences of PARGs from several species are described. PARG is involved in the cellular response to DNA damage and its proper function is associated with the body's response to neoplastic disorder inducing agents and oxidative stress. Expression vectors containing the cDNAs and cells transformed with the vectors are described. Probes and primers that hybridize with the cDNAs are described. Expression of the cDNA in E. coli results in an enzymatically active protein of about 111 kDa and an active fragment of about 59 kDa. Methods …

Sequiterpene Synthase Gene And Protein, Joe Chappell, Bryan T. Greenhagen

Pharmaceutical Sciences Faculty Patents

The invention relates to sesquiterpene synthases and methods for their production and use. Particularly, the invention provides nucleic acids comprising the nucleotide sequence of citrus valencene synthase (CVS) which codes for at least one CVS. The invention further provides nucleic acids comprising the nucleotide sequence coding for amino acid residues forming the tier 1 and tier 2 domains of CVS. The invention also provides for methods of making and using the nucleic acids and amino acids of the current invention.

High-Activity Mutants Of Butyrylcholinesterase For Cocaine Hydrolysis And Method Of Generating The Same, Chang-Guo Zhan, Hoon Cho, Hsin-Hsiung Tai

Pharmaceutical Sciences Faculty Patents

A novel computational method and generation of mutant butyrylcholinesterase for cocaine hydrolysis is provided. The method includes molecular modeling a possible BChE mutant and conducting molecular dynamics simulations and hybrid quantum mechanical/molecular mechanical calculations thereby providing a screening method of possible BChE mutants by predicting which mutant will lead to a more stable transition state for a rate determining step. Site-directed mutagenesis, protein expression, and protein activity is conducted for mutants determined computationally as being good candidates for possible BChE mutants, i.e., ones predicted to have higher catalytic efficiency as compared with wild-type BChE. In addition, mutants A199S/A328W/Y332G, A199S/F227A/A328W/Y332G, A199S/S287G/A328W/Y332G, …

Method For Enhancing Protective Cellular Responses To Genotoxic Stress In Skin, Elaine L. Jacobson, Myron K. Jacobson

Pharmaceutical Sciences Faculty Patents

The present invention is directed to methods of using pro-NAD agents capable of enhancing the dermal and epidermal skin cell NAD content. These pro-NAD agents may be administered topically, orally, or parenterally to enhance DNA repair and other protective responses to DNA damage. The invention further relates to pharmaceutical compositions comprising pro-NAD agents that effectively elevate intracellular NAD content. Finally, the invention relates to the method of using the pro-NAD agents to treat disorders such as sunburn and other skin deterioration that results from DNA damage in skin cells.

Derivatives Of Mithramycin And Methods Of Making And Uses Thereof, Jürgen Rohr, Lily L. Remsing, Mohammad Ner-E-Alam, Jose A. Salas, Carmen Mendez, Alfredo F. Brana, Ana M. Gonzalez

Pharmaceutical Sciences Faculty Patents

The invention, in one aspect, generally relates to mithramycin derivatives from mutated Streptomyces argillaceus and their production. The invention also relates using the derivatives for the treatment of various diseases. Finally, the invention relates to a mutated Streptomyces argillaceus useful in the production of the mithramycin derivatives.

Cytochrome P450 And Uses Of Thereof, Joseph Chappell, Lyle F. Ralston

Pharmaceutical Sciences Faculty Patents

The invention features isolated cytochrome P450 polypeptides and nucleic acid molecules, as well as expression vectors and transgenic plants containing these molecules. In addition, the invention features uses of such molecules in methods of increasing the level of resistance against a disease caused by a plant pathogen in a transgenic plant, in methods for producing altered compounds, for example, hydroxylated compounds, and in methods of producing isoprenoid compounds.

2,6-Disubstituted Piperidines And Piperazine Compounds, Peter A. Crooks, Linda P. Dwoskin, Marlon D. Jones, Dennis Keith Miller, Seth Davin Norholm, Guangrong Zheng, Sairam Krishamurthy

Pharmaceutical Sciences Faculty Patents

The preparation of novel microemulsions to be used as precursors for solid nanoparticles is described. The microemulsion precursors consist of either alcohol-in-fluorocarbon microemulsions, liquid hydrocarbon-in-fluorocarbon microemulsions, or liquid hydrocarbon-in-water microemulsions. The formed solid nanoparticles have diameters below 200 nanometers and can be made to entrap various materials including drugs, magnets, and sensors. The solid nanoparticles can be made to target different cells in the body by the inclusion of a cell-specific targeting ligand. Methods of preparing the novel microemulsion precursors and methods to cure solid nanoparticles are provided.

Use Of Parthenolide Derivatives As Antileukemic And Cytotoxic Agents, Peter A. Crooks, Craig T. Jordan, Xiaochen Wei

Pharmaceutical Sciences Faculty Patents

Compounds of the formula having anti-tumor activity, wherein R₁ and R₂ are as described herein

Methods Of Delaying Development Of Cea-Associated Tumors Using Anti-Idiotype Antibody 3h1, Malaya Chatterjee, Kenneth A. Foon, Sunil K. Chatterjee

Pharmaceutical Sciences Faculty Patents

The present invention provides methods of delaying development of CEA-associated tumors using the anti-idiotype antibody 3H1, particularly in high-risk individuals.

Optical Monitoring System With Molecular Filters, Robert A. Lodder, John Carberry

Pharmaceutical Sciences Faculty Patents

An optical monitoring system for determining the constituents of a sample or specimen. An absorption spectrum is obtained from a sample and is passed through one or more filters having a specified absorption spectrum defined by a single atom or a compound. If the filter's absorption spectrum is included in the sample's absorption spectrum, then the sample contains that atom or compound. The apparatus includes a switching assembly that sequentially places one or more filters into the light path to determine if the subject atom or compound is contained in the sample.

Compounds Of Use In The Treatment Of Epilepsy, Seizure, And Electroconvulsive Disorders, Peter A. Crooks, Aimee K. Bence, David Robert Worthern

Pharmaceutical Sciences Faculty Patents

The present invention provides pharmaceutical preparations and the uses thereof for preventing and/or treating seizures and other electroconvulsive disorders by administering a pharmaceutically effective amount of a therapeutic compound . . .

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Permeable, Water Soluble, Non-Irritating Prodrugs Of Chemotherapeutic Agents With Oxaalkanoic Acids, Peter A. Crooks, Tadeusz Cynkowski, Grazyna Cynkowska, Hong Guo, Paul Ashton

Pharmaceutical Sciences Faculty Patents

The present invention relates to the field of prodrugs of chemotherapeutic agents and method of use thereof.

Microemulsions As Precursors To Solid Nanoparticles, Russell John Mumper, Michael Jay

Pharmaceutical Sciences Faculty Patents

The preparation of novel microemulsions to be used as precursors for solid nanoparticles is described. The microemulsion precursors consist of either alcohol-in-fluorocarbon microemulsions, liquid hydrocarbon-in-fluorocarbon microemulsions, or liquid hydrocarbon-in-water microemulsions. The formed solid nanoparticles have diameters below 200 nanometers and can be made to entrap various materials including drugs, magnets, and sensors. The solid nanoparticles can be made to target different cells in the body by the inclusion of a cell-specific targeting ligand. Methods of preparing the novel microemulsion precursors and methods to cure solid nanoparticles are provided.

Chain-Modified Pyridino-N Substituted Nicotine Compounds For Use In The Treatment Of Cns Pathologies, Peter A. Crooks, Linda Dwoshin, Rui Xu, Joshua T. Ayers

Pharmaceutical Sciences Faculty Patents

Compounds for treating abuse of nicotinic receptor agonists, addiction to psychostimulant drugs, addiction to opiates, addiction to alcohol, addiction to tobacco products, addiction to nicotine, schizophrenia and related diseases, depression and related conditions, Alzheimer's disease, Parkinson's disease, irritable bowel syndrome, and colitis. The compounds competitively inhibit central nervous system acting nicotinic receptor agonists and act at the putative α3β2* and α4β2 neuronal nicotinic receptors in the central nervous system.

Camptothecin Intermediates And Prodrugs And Methods Of Preparation Thereof, Thomas G. Burke, Dennis P. Curran, Wu Du

Pharmaceutical Sciences Faculty Patents

The present invention relates to novel intermediates and prodrugs of camptothecin and related analogs.

Selective Parp-1 Targeting For Designing Chemo/Radio Sensitizing Agents, Marcos Oliveira

Pharmaceutical Sciences Faculty Patents

Poly(ADP-ribose) polymerase-1 (PARP-1) is a central signaling enzyme in a cell nucleus. PARP-1 is a target for the development of radio and chemo sensitizing agents in cancer treatment as well as providing protection from stroke. An SH3 domain and an SH3 ligand domain have now been discovered on the PARP-1 protein. These domains are involved in PARP-1 activation. This discovery makes possible the use of bioinformatics tools for the design of new drugs and strategies for drug target selection, specifically targeting the PARP-1 enzyme.

Cis-2,6-Disubstituted Piperidines For The Treatment Of Psychostimulant Abuse And Withdrawal, Eating Disorders, And Central Nervous System Diseases And Pathologies, Linda P. Dwoskin, Peter A. Crooks, Marlon D. Jones

Pharmaceutical Sciences Faculty Patents

Cis-2,6-disubstituted piperdine analogs, or lobeline analogs, having the general formula...

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Oligonucleotide Delivery Systems For Camptothecins, Thomas Burke, Ayhan S. Demir, Ashok J. Chavan, Danzhou Yang

Pharmaceutical Sciences Faculty Patents

Camptothecin drugs are stabilized in their antitumor active lactone form by complexation with an oligonucleotide including RNA or catalytic RNA. The oligonucleotide-camptothecin drug complex may be incorporated within a macromolecular assembly including both viral and non-viral oligonucleotide vectors. The invention allows combination gene and camptothecin drug therapy.

Synthases, Joseph Chappell, Kathleen R. Manna, Joseph P. Noel, Courtney M. Starks

Pharmaceutical Sciences Faculty Patents

Novel synthases and the corresponding nucleic acids encoding such synthases are disclosed herein. Such synthases possess an active site pocket that includes key amino acid residues that are modified to generate desired terpenoid reaction intermediates and products. Synthase modifications are designed based on, e.g., the three-dimensional coordinates of tobacco 5-epi-aristolochene synthase. with or without a substrate bound in the active site.

Nanoscintillation Systems For Aqueous-Based Liquid Scintillation Counting, Russell J. Mumper, Michael Jay

Pharmaceutical Sciences Faculty Patents

The present invention relates to the use of nanoscintillation systems, or nanoparticles containing fluor molecules, that can be used to detect an electron-emitting or alpha-particle-emitting radioisotope in the absence of organic-solvents commonly used in organic-based liquid scintillation cocktails. The invention also relates to compositions and use of three oil-in-water microemulsion precursors that can be engineered rapidly, reproducibly, and cost-effectively to produce useful nanoparticles less than 100 nanometers.

Permeable, Water Soluble, Non-Irritating Prodrugs Of Chemotherapeutic Agents With Oxaalkanoic Acids, Peter A. Crooks, Tadeusz Cynkowski, Grazyna Cynkowska, Hong Guo, Paul Ashton

Pharmaceutical Sciences Faculty Patents

The present invention relates to the field of prodrugs of chemotherapeutic agents and method of use thereof.

2,6-Disubstituted Piperidines As Modulators Of Nicotinic Acetylcholine Receptor Mediated Neurotransmitter Release, Uptake And Storage, Peter A. Crooks, Linda P. Dwoskin, Dennis Keith Miller, Vladimir P. Grinevich, Seth Davin Norrholm, Guangrong Zheng

Pharmaceutical Sciences Faculty Patents

Compounds used for treating dependence on or withdrawal from a drug of abuse, for an eating disorder or for a CNS disease or pathology . . .

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Pharmaceutical Formulation For Poorly Water Soluble Camptothecin Analogues, Tiang-Xiang Xiang, Bradley D. Anderson

Pharmaceutical Sciences Faculty Patents

The present invention provides a general method to retard the precipitation inception time for poorly water-soluble camptothecin analogues from a supersaturated solution by a chemical conversion approach via pH alteration. This method is successfully utilized to prepare stable parenteral formulations for silatecan 7-t-butyldimethylsilyl-10-hydroxycamptothecin (DB-67), a poorly water-soluble lipophilic camptothecin analogue, in aqueous solutions containing β-cyclodextrin sulfobutyl ether (SBE-CD) or other solubilizing agents. The formulations manufactured by this method are more simple and cost-effective, of higher doses and better quality in terms of manufacture loss and formulation stability, and can be free of organic solvents (e.g., DMSO or N-methyl-2-pyrrolidinone).