University of California

Leidos Biomedical Research, Inc.

Frank McCormick

Adam Renslo

Anna E Maciag

David Turner

Oleg Chertov

Stephan Gysin

Osamu Tetsu

Kenichi Wakita

Joseph Saavedra

Marcin Dyba

Vandana Kumari

Elizabeth D Vo

Man-Tzu Wang

Provided herein, inter alia, are methods and compounds for inhibiting K-Ras and for treating cancer.

K-Ras modulators

Provided herein are the K-Ras inhibitors of the formulae: Also provided are compositions comprising thereof for treating cancer.

Provided herein, inter alia, are methods and compounds of formula (I) for inhibiting K-Ras and for treating cancer. 

The present invention provides method of treating a K-Ras-expressing cancer in a subject comprising administering to the subject a therapeutic amount of prostratin or a prostratin analog, or a salt or isomer thereof. Compositions and kits for treating a K-Rasexpressing cancer in a subject are also provided.

Targeting K-Ras-mediated signaling pathways and malignancy by prostratin

This invention utilizes a two-hybrid system to screen for agents that modulate the ability of a cell to degrade or to accumulate a metabolic product or to selective kill a cell or to selectively express a gene or cDNA in a cell that has a defect in its ability to degrade or to accumulate a metabolic product. One embodiment provides a mammalian cell comprising a nucleic acid encoding a peptide binding domain and an effector gene; a first chimeric protein comprising a nucleic acid binding domain that binds the peptide binding domain attached to the metabolic product or to a ligand that binds to the metabolic product; and a second chimeric protein comprising an expression control protein attached to the metabolic product or to the ligand that binds to the metabolic product such that when the first chimeric protein comprises the metabolic product, the second chimeric protein comprises the ligand and when the first chimeric protein comprises the ligand, the second chimeric protein comprises the metabolic product. The cell is contacted with a test agent and an alteration of expression of the effector gene is detected (if present) where a change in expression of the effector gene in response to the test agent indicates that the test agent modulates the ability of the cell to accumulate or degrade the metabolic product.

Mammalian two-hybrid system for screening for modulators of the accumulation of metabolic products

This invention utilizes a two-hybrid system to screen for agents that modulate the ability of a cell to degrade or to accumulate a metabolic product or to selective kill a cell or to selectively express a gene or cDNA in a cell that has a defect in its ability to degrade or to accumulate a metabolic product. One embodiment provides a mammalian cell comprising a nucleic acid encoding a peptide binding domain and an effector gene; a first chimeric protein comprising a nucleic acid binding domain that binds the peptide binding domain attached to the metabolic product or to a ligand that binds to the metabolic product; and a second chimeric protein comprising an expression control protein attached to the metabolic product or to the ligand that binds to the metabolic product such that when the first chimeric protein comprises the metabolic product, the second chimeric protein comprises the ligand and when the first chimeric protein comprises the ligand, the second chimeric protein comprises the metabolic product. The cell is contacted with a test agent and in alteration of expression of the effector gene is detected (if present) where a change in expression of the effector gene in response to the test agent indicates that the test agent modulates the ability of the cell to accumulate or degrade the metabolic product.

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San Francisco, CA, United States of America

Frank McCormick