Columbia University

Whitehead Institute for Biomedical Research

Combinatorx, Incorporated

Massachusetts Institute of Technology

Harvard College

Prolexys Pharmaceuticals, Inc.

Other

Brent R Stockwell

Rachid Skouta

Scott E Dixon

Alexis Borisy

Michael Andrew Foley

Curtis Keith

Wan Seok Yang

Stuart L Schreiber

Matthew D Shair

Paul B Robbins

Vernon M Ingram

Longwu Qi

Barbara J Blanchard

Robert Selliah

Raj Gopal Venkat

Sudhir R Sahasrabudhe

Matthew Welsch

Derek S Tan

Michael A Foley

Arie Zask

Moritz Von Rechenberg

Hynek Wichterle

John M Peltier

Emily Rhodes Lowry

Rohitha Sriramaratnam

Robert R Becklin

Kenichi Shimada

Cindy Lou Chepanoske

Marie-Helene Larraufie

Keith Simmon

Eugene Y Zhen

Pieter Bos

Sebastian Thams

Keith Simmons

John M Pelter

Eugene Zhen

The present invention provides, inter alia, a compound having the structure: Also provided are compositions containing a pharmaceutically acceptable carrier and one or more compounds according to the present invention. Further provided are methods for treating or ameliorating the effects of a disorder in a subject, methods of suppressing the toxicity of endoplasmic reticulum (ER) stress in a subject, methods of treating or ameliorating the effects of a disease involving axon degeneration in a subject, and methods for treating or ameliorating the effects of a neurodegenerative disease.

Substituted pyrrolo[2,3-b]pyridines for suppressing toxic endoplasmic reticulum stress

The present invention provides, inter alia, a compound having the structure of Formula (I). Also provided are compositions containing a pharmaceutically acceptable carrier and a compound according to the present invention. Further provided are methods for treating or ameliorating the effects of an excitotoxic disorder in a subject, methods of modulating ferroptosis in a subject, methods of reducing reactive oxygen species (ROS) in a cell, and methods for treating or ameliorating the effects of a neurodegenerative disease. 

Compounds, compositions, and methods for modulating ferroptosis and treating excitotoxic disorders

The present invention provides, inter alia, a compound according to formula (I): Also provided are compositions containing a pharmaceutically acceptable carrier and a compound according to the present invention. Further provided are methods for regulating GPX4 in a cell and methods for inducing ferroptosis in a cell.

Small molecule ferroptosis inducers

The present invention provides, inter alia, a compound having the structure: Also provided are compositions containing a pharmaceutically acceptable carrier and a compound according to the present invention. Further provided are methods for treating or ameliorating the effects of an excitotoxic disorder in a subject, methods of modulating ferroptosis in a subject, methods of reducing reactive oxygen species (ROS) in a cell, and methods for treating or ameliorating the effects of a neurodegenerative disease.

The present invention provides, inter alia, compounds having the structure of formula (I): Compositions containing such compounds are also provided. Methods for using such compounds or compositions for treating or ameliorating the effects of a cancer having a cell that harbors an oncogenic RAS mutation, for modulating a lipoxygenase in a ferroptosis cell death pathway, and for depleting reduced glutathione (GSH) in a cell harboring an oncogenic RAS mutation are further provided. 

Carbonyl erastin analogs and their use

The present invention provides, inter alia, compounds having the structure: wherein R, Rand n are as disclosed herein, that selectively bind a RAS protein at two or more sites and methods for their synthesis. Compositions and kits containing the compounds, as well as methods of using the compounds and compositions for ameliorating or treating the effects of a disease associated with altered RAS signaling, such as a cancer, in a subject and methods for effecting cancer cell death are also provided herein. Methods of identifying a multivalent compound which binds selectively to a target protein also are provided herein.

Multivalent RAS binding compounds

The present invention provides, inter alia, compounds having the structure (1) compositions containing such compounds are also provided. Methods for using such compounds or compositions for treating or ameliorating the effects of a cancer having a cell that harbors an oncogenic RAS mutation, for modulating a lipoxygenase in a ferroptosis cell death pathway, and for depleting reduced glutathione (GSH) in a cell harboring an oncogenic RAS mutation are further provided. 

Quinazolinone-based oncogenic-RAS-selective lethal compounds and their use

The present invention provides, inter alia, a compound having the structure: (Formula (I). Also provided are compositions containing a pharmaceutically acceptable carrier and a compound according to the present invention. Further provided are methods for treating or ameliorating the effects of an excitotoxic disorder in a subject, methods of modulating ferroptosis in a subject, methods of reducing reactive oxygen species (ROS) in a cell, and methods for treating or ameliorating the effects of a neurodegenerative disease. 

Compounds with cancer cell specific lethality are provided. In particular, RAS-selective lethal compounds and compositions are provided. Also provided are methods of screening for such compounds and methods of treating a condition in a mammal, by administering to the mammal a therapeutically effective amount of such compounds or compositions.

Oncogenic-RAS-signal dependent lethal compounds

The invention relates to methods for identifying agents, which induce oxidative cell death in a tumor cell. The invention further relates to methods for identifying tumor cells, which are sensitive to agents that induce oxidative cell death. The invention also relates to methods for identifying subjects who are suffering from tumors, which are sensitive to agents that induce oxidative cell death.

Assays for non-apoptotic cell death and uses thereof

The invention relates to methods of screening for binding partners, especially binding partners essential for the biological activity of erastin (e.g. VDACs such as VDAC3). The invention also provides reagents and methods for effective killing of cancer cells with erastin and related compounds or derivatives.

Quinoxaline derivatives as antitumor agents

The present invention relate to methods of identifying a genotype-selective agent. In certain embodiments, the invention relates to agents that are selectively toxic to engineered human tumorigenic cells.

Identification of genotype-selective anti-tumor agents

Erastin and erastin binding proteins, and uses thereof

Growing community of inventors

New York, NY, United States of America

Brent R Stockwell