Cadus Technologies, Inc.

Cadus Pharmaceutical Corp.

Myriad Genetics, Inc.

Other

John P Manfredi

Joshua Trueheart

Christine A Klein

Dana M Fowlkes

Jeremy I Paul

Andrew J Murphy

James R Broach

Jim Broach

Andrew J M Murphy

Mark B Anderson

Warren S Weiner

Ruth J Walton

Kenton Zavitz

Rachel M Slade

Yevgeniya Klimova

Robert J Halter

Andrew Gassman

Ashantai J Yungai

Jon Adam Willardsen

Leena Bhoite

Benjamin K Benton

Meng-Yu Wu

Jay Zhang

The present disclosure relates to novel indole and tetrahydroindole core compounds useful for the treatment of disorders associated with a defect in vesicular transport (e.g., axonal transport).

Compounds for Alzheimer's disease

Yeast cells are engineered to express both a surrogate of a pheromone system protein (e.g., enzymes involved in maturation of &#x3b1;-factor, transporters of a-factor, pheromone receptors, etc.) and a potential peptide modulator of the surrogate, in such a manner that the inhibition or activation of the surrogate affects a screenable or selectable trait of the yeast cells. Various additional features improve the signal-to-noise ratio of the screening/selection system.

Yeast cells engineered to produce pheromone system protein surrogates, and uses therefor

The present invention pertains to novel yeast cells which are useful for the expression of heterologous G protein coupled receptors. The yeast cells of the present invention can be used in screening assays which can be used to screen for modulators of G protein coupled receptors. Specifically, the invention provides novel yeast cells which express a heterologous G protein coupled receptor and mutant and/or chimeric G protein subunit molecules which serve to functionally integrate the heterologous into the pheromone signaling pathway of the yeast cell. The invention also provides for the expression of heterologous G protein coupled receptors which are functionally integrated into the yeast cell membrane using a yeast &#x3b1; factor leader sequence. Drug discovery assays using the subject yeast cells are also provided.

Yeast cells expressing modified G proteins and methods of use therefor

The invention provides recombinant cells that have been engineered such that ligand stimulation of a receptor expressed by the cells leads to amplified signal transduction responses. In one embodiment, the receptor-expressing cells have been engineered to carry a heterologous DNA construct comprising a gene encoding a protein that activates the signal transduction pathway, which gene is operatively linked to a promoter that is responsive to activation of the signal transduction pathway. Stimulation of the receptor by a ligand leads to expression of the heterologous DNA construct encoding the protein that activates the signal transduction pathway such that signals generated by ligand binding to the receptor are amplified. Preferred cells are yeast cells expressing heterologous G protein coupled receptors functionally coupled to the yeast pheromone response pathway and overexpressing Ste5p, Ste4p, Ste12p, Ste11p or a dominant truncation allele of Ste20 via a pheromone-responsive promoter. The invention further provides cells expressing a heterologous receptor, wherein an endogenous gene encoding a protein that negatively regulates an endogenous signal transduction pathway is mutated to render the protein nonfunctional such that signals generated by ligand binding to the receptor are amplified. The invention further provides cells expressing a heterologous receptor, wherein an endogenous gene encoding a protein that positively regulates an endogenous signal transduction pathway is mutated to a supersensitive form such that the sensitivity of the pathway to ligand stimulation is increases. Methods of using the cells of the invention to identify receptor modulators are also provided.

Cell having amplified signal transduction pathway responses and uses therefor

The present invention makes available a rapid, effective assay for screening and identifying pharmaceutically effective compounds that specifically interact with and modulate the activity of a cellular receptor or ion channel. The subject assay enables rapid screening of large numbers of polypeptides in a library to identifying those polypeptides which induce or antagonize receptor bioactivity. The subject assay is particularly amenable for identifying surrogate ligands for orphan receptors.

Methods and compositions for identifying receptor effectors

Yeast cells engineered to produce pheromone system protein surrogates and uses therefor

An in vitro method for detecting protein-protein interactions is provided, in which two fusion proteins are prepared and allowed to interact with each other in a substantially cell free environment. The interaction between the two fusion proteins leads to protein trans-splicing, generating an active and detectable reporter.

Method of detecting protein-protein interactions

A method for detecting protein-protein interactions is provided, in which two fusion proteins are prepared and allowed to interact with each other. The interaction between the two fusion proteins leads to protein trans-splicing, generating an active and detectable reporter.

A method for detecting protein-protein interactions is provided, in which two fusion proteins are prepared and allowed to interact with each other in yeast cells. The interaction between the two fusion proteins leads to protein trans-splicing, generating an active and detectable reporter.

Yeast two-hybrid system and use thereof

A method for selecting compounds capable of modulating protein-protein interactions is provided, in which two fusion proteins are prepared and allowed to interact with each other in the presence of test compounds. The interaction between the two fusion proteins leads to protein trans-splicing, producing an active reporter. Compounds that disrupt or enhance protein-protein interactions can be selected based on the presence or absence of the active reporter.

Screen assay for selecting protein-protein interaction modulators

The present invention makes available a rapid, effective assay for screening and identifying pharmaceutically effective compounds that specifically interact with and modulate the activity of a cellular receptor or ion channel. The subject assay enables rapid screening of large numbers of polypeptides in a yeast expression library to identifying those polypeptides which induce or antagonize receptor bioactivity. The subject assay is particularly amenable for identifying surrogate ligands for orphan receptors.

Growing community of inventors

Ossining, NY, United States of America

John P Manfredi