Northwestern University

The General Hospital Corporation

Bial - R&d Investments, S.a.

Lysosomal Therapeutics Inc.

Dimitri Krainc

Richard B Silverman

Jianbin Zheng

Andrew Charles Good

Renato T Skerlj

Peter T Lansbury

Elyse Marie Josee Bourque

Michael Schwake

Hyunkyung Jeong

Florian Then

Elyse Marie Josée Bourque

Disclosed are new small molecules having a substituted pyrimidine or substituted fused pyrimidine core structure and the uses thereof for modulating glucocerebrosidase activity. Also disclosed are pharmaceutical compositions comprising the small molecules which may be administered in methods of treating diseases or disorders associated with glucocerebrosidase activity, including Gaucher's disease and neurological diseases and disorders such as genetic and sporadic synucleinopathies, including Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy associated with aberrant glucocerebrosidase activity. The small molecules may contain a fluorophore or may be conjugated to a fluorophore in order to prepare a fluorescent probe for use in high throughput screening methods to identify new modulators of glucocerebrosidase activity via fluorescence polarization.

Substituted fused pyrimidine compounds and uses thereof

The invention provides substituted pyrrolo[1,2-a]pyrimidines and related organic compounds, compositions containing such compounds, medical kits, and methods for using such compounds and compositions to treat medical disorders, e.g., Gaucher disease, Parkinson's disease, Lewy body disease, dementia, or multiple system atrophy, in a patient. Exemplary substituted pyrrolo[1,2-a]pyrimidines compounds described herein include substituted 2,4-dimethyl-N-phenylpyrrolo[1,2-a]pyrimidine-8-carboxamide compounds and variants thereof.

Substituted pyrrolo[1,2-a]pyrimidines and their use in the treatment of medical disorders

Disclosed are new small molecules having a substituted quinazoline core structure and the uses thereof for modulating glucocerebrosidase activity. Also disclosed are pharmaceutical compositions comprising the small molecules or activated glucocerebrosidase conjugated to the small molecules, which compositions may be administered in methods of treating diseases or disorders associated with glucocerebrosidase activity, including neurological diseases and disorders such as Gaucher's disease and Parkinson's disease.

Substituted quinazoline compounds and uses thereof for modulating glucocerebrosidase activity

Disclosed are new small molecules having a pyrrolopyrimidine core structure and the uses thereof for modulating glucocerebrosidase activity. Also disclosed are pharmaceutical compositions comprising the small molecules which may be administered in methods of treating diseases or disorders associated with glucocerebrosidase activity, including neurological diseases and disorders such as Gaucher's disease and Parkinson's disease. The small molecules may be utilized to generate activated glucocerebrosidase. The activated glucocerebrosidase thusly generated can be administered in enzyme replacement therapy and/or utilized in screening assays for new small molecules that bind to the activated glucocerebrosidase and/or modulate the activity of the activated glucocerebrosidase.

Pyrrolopyrimidine compounds and uses thereof for modulating glucocerebrosidase activity

Disclosed are new small molecules having a 4-methylpyrrrolo[1,2-a]pyrimidine-8-carboxamide core structure and the uses thereof for modulating glucocerebrosidase activity. Also disclosed are pharmaceutical compositions comprising the small molecules which may be administered in methods of treating diseases or disorders associated with glucocerebrosidase activity, including neurological diseases and disorders such as Gaucher's disease and Parkinson's disease. The small molecules may contain a fluorophore or may be conjugated to a fluorophore in order to prepare a fluorescent probe for use in high throughput screening methods to identify new modulators of glucocerebrosidase activity via fluorescence polarization.

Substituted 4-methyl-pyrrolo[1,2-a]pyrimidine-8-carboxamide compounds and uses thereof for modulating glucocerebrosidase activity

A group of LIMP-2 peptides, LIMP-2 polypeptides, variants thereof, and pharmaceutical compositions comprising the LIMP-2 peptides, LIMP-2 polypeptides, or variants thereof are described. The disclosed peptides and polypeptides preferably comprise an amino acid sequence that is sufficient for providing a biological activity associated with LIMP-2, which may include binding and/or activating biological molecules such as &#x3b2;-glucocerebrosidase and binding viral protein 1 (VP1) of enterovirus 71 (E71) or coxsackievirus A16 (CA16). Also disclosed are methods of using the LIMP-2 peptides, LIMP-2 polypeptides, and variants thereof as therapeutics for treating diseases and disorders associated with &#x3b2;-glucocerebrosidase activity in subjects in need thereof.

Lysosome membrane protein 2 (LIMP-2) based peptides and related uses

Substituted 4-methyl-pyrrolo[1,2-A]pyrimidine-8-carboxamide compounds and uses thereof for modulating glucocerebrosidase activity

This invention includes, in part, methods of preparing acetylated Huntingtin (Htt) polypeptides, acetylated Htt polypeptide antigens, and antibodies that specifically recognize acetylated epitopes on Htt polypeptides. The invention also relates, in part, to the preparation and use of antibodies that specifically recognize and bind to acetylated epitopes on acetylated Htt polypeptides when an acetylated residue on the Htt polypeptide is a lysine that corresponds to K444 residue of full-length, wild-type Htt polypeptide. In some aspects, the invention includes hybridoma cell lines that produce antibodies that specifically bind acetylated Htt polypeptide and also includes antibodies and antigen-binding fragments thereof produced using polypeptides of the invention.

Anti-acetylated huntingtin antibodies and uses therof

The invention relates to methods and products for deregulating gene transcription in neurodegenerative disease associated with an expanded polyglutamine tract in mutant proteins. The invention is useful for preventing and treating diseases associated with expanded polyglutamine tracts, including Huntington's disease. The methods and compositions of the invention are also useful for identifying additional pharmaceutical agents for preventing and treating diseases associated with expanded polyglutamine tracts.

Growing community of inventors

Chicago, IL, United States of America

Dimitri Krainc