University of California

Olema Pharmaceuticals, Inc.

Other

California Biotechnology Inc.

Peter J Kushner

David C Myles

Cyrus L Harmon

Paul Webb

Brian L West

John D Baxter

C Anthony Hunt

Robert J Fletterick

Richard L Wagner

Renee Williard

Gabriella Lopez

Thomas S Scanlan

Andrew K Shiau

James J Apriletti

Rosalie M Uht

Karen D Talmadge

Ira D Goldfine

Keith R Yamamoto

Jeffrey M Arbeit

Betty A Maddux

Michael Campbell

Leslie Carol Hodges Gallagher

Jack F Youngren

Birgit Anderegg

John Kerner

Claire L Cofer

Jeffrey S Friedman

Beatrice Darimont

Richard Sun

Weijun Feng

Leslie Hodges Gallagher

Provided herein are methods of administering estrogen receptor antagonists for use in treatment of cancer. In some embodiments, estrogen receptor antagonists provided herein are tetrahydro pyrido[3,4-b] indole compounds. In some embodiments, provided antagonists are complete estrogen receptor antagonists.

Regimens of estrogen receptor antagonists

The present disclosure provides tetrahydro-1H-pyrido[3,4-b]indole compounds or a pharmaceutically acceptable salt, solvate, hydrate, prodrug, stereoisomer, tautomer, rotamer, N-oxide and/or substituted derivative or, optionally in a pharmaceutical composition, for the modulation of disorders mediated by estrogen, or other disorders as more fully described herein.

Tetrahydro-1H-pyrido [3,4-b]indole anti-estrogenic drugs

Tetrahydro-1H-pyrido[3,4-b]indole anti-estrogenic drugs

Benzopyran compounds with strong anti-estrogenic activity and essentially no estrogenic activity are provided, which are OP-1038, which is 3-(4-hydroxyphenyl)-4-methyl-2-(4-{2-[(3R)-3-methylpyrrolidin-1-yl]ethoxy}phenyl)-2H-chromen-7-ol, and OP-1074, which is (2S)-3-(4-hydroxyphenyl)-4-methyl-2-(4-{2-[(3R)-3-methylpyrrolidin-1-yl]ethoxy}phenyl)-2H-chromen-7-ol. OP-1074 is a pure anti-estrogen when tested in the agonist mode and a complete anti-estrogen when tested in the antagonist mode. These compounds are useful for the treatment or prevention of a variety of conditions that are modulated through the estrogen receptor in mammals including humans.

Benzopyran compounds, compositions and uses thereof

A method of treatment is disclosed whereby cancer cells are brought into contact with a formulation comprising an inhibitor of tyrosine kinase receptors. The formulation may be comprised of an injectable carrier and two or more tyrosine kinase receptor inhibitors which may be nordihydroguaiarectic acid (NDGA) and doxorubicin.

Tyrosine kinase receptor antagonists and methods of treatment for breast cancer

The present invention is directed to compounds, compositions thereof, and the use of the compounds and compositions for the treatment and prevention of breast cancer. In one embodiment, the present invention relates to the use of a substituted triphenyl butene or prodrug thereof for the treatment of breast cancer in mono-therapy or in combination therapy, or for a reduction in the recurrence rate of previously-treated breast cancer.

Substituted triphenyl butenes

The present invention relates to methods and agonist/antagonist compounds for modulating nuclear receptor coactivator binding. The invention includes a method for identifying residues comprising a coactivator binding site for a nuclear receptor of interest. Also included is a method of identifying agonists and/or antagonists that bind to a coactivator binding site of a nuclear receptor of interest. Agonists and antagonists of coactivator binding to nuclear receptors also are provided. The invention is exemplified by identification and manipulation of the coactivator binding site of the thyroid receptor (TR), and compounds that bind to this sites. The methods can be applied to other nuclear receptors including RAR, RXR, PPAR, VDR, ER, GR, PR, MR, and AR.

Methods for modulating nuclear receptor coactivator binding

The present invention provides novel assay methods for identifying compounds that may have both estrogen agonist and antagonist properties. In particular, the assay use cells comprising promoters having an AP1 site linked to a reporter gene. Compounds capable of inducing or blocking expression of the reporter gene can thus be identified. The compounds may be further tested for the ability to modulate the standard estrogen response, as well.

Methods for screening compounds for estrogenic activity

The present invention relates to improved compositions and methods for assaying the efficacy of novel drugs functioning either as agonists or antagonists at nuclear receptors. In particular, the invention provides transgenic non-human animals comprising a human steroid hormone receptor gene operably linked to a promoter which directs expression of the steroid hormone receptor gene in an epithelial cell of the non-human animals.

Expression of human estrogen receptors in transgenic mice

The present invention provides new methods, particularly computational methods, and compositions for the generation of nuclear receptor synthetic ligands based on the three dimensional structure of nuclear receptors, particularly the thyroid receptor (herein referred to as &ldquo;TR&rdquo;). Also provided are crystals, nuclear receptor synthetic ligands, and related methods.

Nuclear receptor ligands and ligand binding domains

Compositions comprising inhibitors of estrogen response

This invention provides methods for modulating gene expression at the transcriptional level. In particular, the methods involve tethering a transcriptional coactivator to a DNA binding domain that is specific for a target nucleic acid sequence and contacting the coactivator with a transcription factor. The transcription factor triggers or represses transcription mediated by the coactivator. Methods for identifying compounds that are able to modulate gene expression are also provided.

Methods to screen for transcription factor-coactivator interactions

Growing community of inventors

San Francisco, CA, United States of America

Peter J Kushner