Icahn School of Medicine at Mount Sinai

Pharmacopeia Inc.

Columbia University

Cold Spring Harbor Laboratory

N.v. Organon

The United States Government As Represented by the Department of Veterans Affairs

Msd Oss B.v.

Wyeth

Case Western Reserve University

Otsuka Pharmaceutical Factory, Inc.

Merck Sharp + Dohme B.v.

Atux Iskay LLC

Pharmacopeia Drug Discovery, Inc.

Michael H Ohlmeyer

Lawrence Wayne Dillard

John C Reader

Irina Neagu

Koc-Kan Ho

Michael H Wigler

W Clark Still

Nilesh Zaware

David Kastrinsky

Yajing Rong

Jui-Hsiang Chan

Nasrin Ansari

Jeffrey John Letourneau

Ian Henderson

Patrick Anthony Jokiel

Susan Elizabeth Napier

Andrew Laird Roughton

Goutham Narla

John J Baldwin

Vidyadhar Madhav Paradkar

David Jonathan Bennett

Michelle Lee Morris

Ming-Ming Zhou

Paul David Ratcliffe

Christopher Mark Riviello

John Richard Morphy

Andrew Stanley Edwards

Adam Vincek

Dongming Cai

Matthew David Galsky

Kurt William Saionz

Takashi Okamura

Andrew John Cooke

David J Diller

Steven G Kultgen

Andrew Roughton

Koushi Iwata

Tadao Shibutani

Andrew Cooke

Adolph C Bohnstedt

Ronald Palin

Celia Kingsbury

Jurgen Schulz

Duncan Robert McArthur

Fiona Jeremiah

Neil Dhawan

Yingchun Lu

Koc-Kan Hoc

Koc Kan Ho

Suzanna Katz

Daniel McQuaid

Narla Goutham

Jui Hsiang Chan

Schulz Jurgen

Jeremiah Fiona

Duncan Robert Mcarthur

Jeffrey Letourneau

3-Diarylmethylenes are disclosed. The compounds activate PP2A, suppress oncogenic kinase signaling, and negatively regulate MYC and MYCN in cancer. The compounds also induce FOXO transcription factor translocation to the nucleus by modulating PP2A and, as a consequence, exhibit anti-proliferative effects. They are useful in the treatment of a variety of disorders, including as a monotherapy in cancer treatment, or used in combination with other drugs to restore sensitivity to chemotherapy where resistance has developed.

3-diarylmethylenes and uses thereof

A genus of dihydropyridine chemical modulators of synaptojanin is disclosed. These modulators are selective inhibitors of synaptojanin 1 and may be used to treat cognitive impairment or traumatic brain injury, including promoting regeneration in cases of traumatic brain injury, or for treating neurodegenerative disorders.

Dihydropyridines for the treatment of cognitive impairment or traumatic brain injury

A genus of arylsulfonamide derivatives of heterocyclic constrained tricyclic compounds is disclosed. The compounds are of the following genus:  The compounds induce FOXO1 transcription factor translocation to the nucleus by modulating PP2A and, as a consequence, exhibit anti-proliferative effects. They are useful in the treatment of a variety of disorders, including as a therapy in cancer treatment, or used in combination with other drugs to restore sensitivity to chemotherapy where resistance has developed.

Heterocyclic constrained tricyclic sulfonamides as anti-cancer agents

A method of treating cancer in a subject in need thereof includes administering to the subject therapeutically effective amounts of a PP2A activator and a protein kinase inhibitor.

Compositions and methods for treating cancer

A process for the stereoselective synthesis of chiral 3-heterocyclyl-1,2-dihydroxy cyclohexanes is disclosed. The process involves reacting a tricyclic nitrogenous heterocycle with an allyl carbonate in the presence of a chiral palladium catalyst followed by oxidation of the olefinic bond to provide 3-heterocyclyl-1,2-dihydroxy cyclohexanes, cyclopentanes and corresponding alicyclic heterocycles. Also disclosed are methods for converting the heterocyclyl-1,2-dihydroxy cyclohexanes to 2-amino-6-(heteroaryl)cyclohexanols (and related cyclic compounds).

Stereospecific process for 3-heterocyclylcycloaliphatic-1,2-diols

Cyclic vinylogous amides of Formula I are disclosed The compounds are useful for treating diseases that arise from inappropriate activity of proteins containing an acetyl-lysine. The compositions comprise a genus of cyclic vinylogous amides that are inhibitors of bromodomain.

Cyclic vinylogous amides as bromodomain inhibitors

Tricyclic chemical modulators of protein phosphatase 2A are disclosed. The compounds are useful to treat cancer, age-onset proteotoxicity, stress-induced depression, inflammation, and acne. The compounds are of the following phenothiazine and dibenzoazepine compounds and similar genera: 

Constrained tricyclic sulfonamides

A genus of arylsulfonamide derivatives of aminocycloalkanols is disclosed. The compounds are of the following genus: The compounds induce FOXO1 transcription factor translocation to the nucleus by modulating PP2A and, as a consequence, exhibit anti-proliferative effects. They are useful in the treatment of a variety of disorders, including as a monotherapy in cancer treatment, or used in combination with other drugs to restore sensitivity to chemotherapy where resistance has developed.

Sulfonamides derived from tricyclyl-2-aminocycloalkanols as anticancer agents

Cyclic vinylogous amides of Formula I are disclosed  The compounds are useful for treating diseases that arise from inappropriate activity of proteins containing an acetyl-lysine. The compositions comprise a genus of cyclic vinylogous amides that are inhibitors of bromodomain.

Tricyclic chemical modulators of FOXO transcription factor proteins are disclosed. The compounds are useful to treat cancer, age-onset proteotoxicity, stress-induced depression, inflammation, and acne. The compounds are of the following and similar genera: in which Het is an aromatic heterocyclic ring and Y is a point of attachment of various side chains and rings. An example of such a compound is 4-chloro-N-(3-(10,11-dihydro-5H-benzo[b]pyrido[2,3-f]azepin-5-yl)propyl)benzenesulfonamide: 

Tricyclic heterocycles as anticancer agents

Tricyclic chemical modulators of FOXO transcription factor proteins are disclosed. The compounds are useful to treat cancer, age-onset proteotoxicity, stress-induced depression, inflammation, and acne. The compounds are of the following phenothiazine, dibenzoazepine and annulene and similar genera: 

Tricyclic compounds as anticancer agents

The present invention relates to anti-cancer therapeutics. In certain aspects, cancers are treated with a combination of an anti-EGFR agent and an agent that increases the activity of the KLF6 tumor suppressor gene and/or an agent that increases activity of the FOXO1 tumor suppressor gene. In a preferred aspect, the anti-EGFR agent erlotinib a tricyclic agent compound, are used in combination to treat non-small cell lung cancer in a patient with primary or acquired drug resistance to erlotinib, and wherein the tricyclic agent is administered in an amount that does not lead to a substantial central nervous system effect. In additional aspects, the invention relates to compositions and kits useful for treating cancers, methods for screening for compounds that enhance the activity of anti-EGFR agent, and methods for determining whether a patient will respond to anti-EGFR therapy.

Method and compositions for treating cancer and related methods

Growing community of inventors

Plainsboro, NJ, United States of America

Michael H Ohlmeyer