University of Kentucky Research Foundation

Columbia University

University of Michigan

Chang-Guo Zhan

Fang Zheng

Wenchao Yang

Hsin-Hsiung Tai

Hoon Cho

Donald W Landry

Liu Xue

Shurong Hou

Ziyuan Zhou

Shi-Xian Deng

Young Min Kwon

Roger K Sunahara

Victor C Yang

James H Woods

John J Tesmer

Diwahar L Narasimhan

Joanne MacDonald

Christopher D Spilling

Robert A Yokel

Wesley R Harris

Tien-Yi Lee

Daquan Gao

Vinod Kasam

Kai Ding

Mei-Chuan Holden Ko

Dong-Eun Kim

Kyung Bo Kim

Lei Fang

Xiaoqin Huang

Adel Hamza

Chunhui Zhang

Na-Re Lee

Xiabin Chen

Kyung-Bo Kim

Wooin Lee

Zach Miller

Do-Min Lee

Shuo Zhou

Joanne Macdonald

Victor Yang

Compositions and methods are provided for use in binding opioids, such as 6-MAM, morphine, heroin, hydrocodone, oxycodone, meperidine, and fentanyl, while avoiding binding to OUD treatment agents, such as naloxone and naltrexone. Methods are also provided for use in a systematic structure-based virtual screening and design approach for identification of such antibodies. Methods are also provided for use in treating OUD. Methods are also provided for use in detecting an opioid in a sample.

Compounds and methods for use in connection with opioid use disorders

Compounds and compositions are provided that can inhibit microsomal prostaglandin E synthase-1 (mPGES-1). The compounds and compositions can reduce inflammation in a subject, such as inflammation caused by an inflammation disorder or symptoms thereof. Pharmaceutical compositions comprising the compound are also provided. Furthermore, methods are provided for reducing inflammation and/or inhibiting mPGES-1. The methods can comprise administering an effective amount of the composition to a subject.

Prostaglandin E synthase inhibitors and methods for utilizing the same

The presently-disclosed subject matter describes fusion proteins comprising butyrylcholinesterase (BChE) having an improved production yield and biological half-life and nucleotides encoding the same.

Increased polypeptide production yields of butyrylcholinesterase polypeptides for therapeutic use

A method of treating opioid use disorder involves administering a selective butyrylcholinesterase (BChE) inhibitor.

Butyrylcholinesterase inhibitors for treatment of opioid use disorder

A method of treating pain is disclosed, which involves administering an effective amount of lapatinib or a pharmaceutically-acceptable salt thereof to a subject in need of treatment for pain.

Methods of treating pain and/or inflammatory disorders using lapatinib

Provided are mutant cocaine esterase polypeptides and PEGylated formulations thereof.

Mutants of cocaine esterase

The presently-disclosed subject matter includes isolated polypeptides that comprise a butyrylcholinestrase (BChE) polypeptide and a second polypeptide. The BChE polypeptide as well as the second polypeptide can be variants and/or fragments thereof. The presently-disclosed subject matter also includes a pharmaceutical composition that comprises the present isolated polypeptide and a suitable pharmaceutical carrier. Further still, methods are provided for treating cocaine-induced conditions, and comprise administering the isolated polypeptide and/or pharmaceutical compositions thereof to an individual.

Cocaine hydrolase-FC fusion proteins for cocaine and methods for utilizing the same

The Bacterial cocaine esterase (CocE) mutants disclosed herein each have enhanced catalytic efficiency for (&#x2212;)-cocaine, as compared to CocE mutants in the prior art, including CocE mutant E172-173. The presently-disclosed subject matter further includes a pharmaceutical composition including a mutant of bacterial cocaine hydrolase, as described herein, and a suitable pharmaceutical carrier. The presently-disclosed subject matter further includes a method of treating a cocaine-induced condition comprising administering to an individual an effective amount of a mutant of bacterial cocaine hydrolase variant, as disclosed herein, to accelerate cocaine metabolism and produce biologically inactive metabolites.

High activity mutants of cocaine esterase for cocaine hydrolysis

Compounds useful for inhibiting the immunoproteasome have the formula of Methods and compounds for inhibiting the immunoproteasome, particularly, immunoproteasome inhibitors with non-peptide scaffolds, are described.

Selective immunoproteasome inhibitors with non-peptide scaffolds

Compounds of formula (I) are useful for inhibiting a proteasome in a cell. Compounds, pharmaceutical compositions and methods of use are provided herein.

Proteasome inhibitors

Butyrylcholinesterase (BChE) polypeptide variants of the presently-disclosed subject matter have enhanced catalytic efficiency for (&#x2212;)-cocaine, as compared to wild-type BChE. Pharmaceutical compositions of the presently-disclosed subject matter include a BChE polypeptide variant having an enhanced catalytic efficiency for (&#x2212;)-cocaine. A method of the presently-disclosed subject matter for treating a cocaine-induced condition includes administering to an individual an effective amount of a BChE polypeptide variant, as disclosed herein, to lower blood cocaine concentration.

High activity mutants of butyrylcholinesterase for cocaine hydrolysis

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, A199S/F227A/S287G/A328W/Y332G, and A199S/F227A/S287G/A328W/E441D all have enhanced catalytic efficiency for (&#x2212;)-cocaine compared with wild-type BChE.

High-activity mutants of butyrylcholinesterase for cocaine hydrolysis and method of generating the same

Growing community of inventors

Lexington, KY, United States of America

Chang-Guo Zhan