Harvard College

Nuvalent, Inc.

The Procter Gamble Company

Other

Taiho Pharmaceutical Company Limited

Matthew D Shair

Henry Efrem Pelish

Scot Richard Mente

Joshua Courtney Horan

Anupong Tangpeerachaikul

Xinxing Tang

Andrew G Myers

Juergen Ramharter

Alec Nathanson Flyer

Hong Myung Lee

Cristina Montserrat Nieto-Oberhuber

Chong Si

Jae Young Ahn

Brian Bor-Jen Liau

Stuart L Schreiber

Alan Roy Katritzky

Brent R Stockwell

Eric Block

Derek S Tan

Michael A Foley

Robert Wayne Glenn, Jr

Matthew David Butts

Thomas Ehlis

Joseph Anthony Lupia

Robert Wayne Glenn

Randall W King

Baudouin Gerard

Alexander Arefolov

Brian Andrew Sparling

Nicholas Westwood

Kristin Lynne Andrews

Gojko Lalic

Yuting Sun

Gregory A Korbel

Jennifer E Ring

Maria Paola Castaldi

Grace L Williams

Astrid S Clarke

Eun Sun Park

David Moebius

Anthony William George Burgett

Disclosed are heterocyclic heteroaromatic macrocyclic ether compounds, pharmaceutically acceptable salts of the compounds and pharmaceutical compositions thereof. Also disclosed are methods of treating or preventing cancer using the heterocyclic heteroaromatic macrocyclic ether compounds, pharmaceutically acceptable salts of the compounds, and pharmaceutical compositions thereof.

Heteroaromatic macrocyclic ether chemotherapeutic agents

Disclosed are heterocyclic heteroaromatic macrocyclic ether compounds of Formula (I): pharmaceutically acceptable salts of the compounds and pharmaceutical compositions thereof. The disclosure further relates to methods of treating or preventing cancer using the heterocyclic heteroaromatic macrocyclic ether compounds, pharmaceutically acceptable salts of the compounds and pharmaceutical compositions thereof.

Disclosed are amino-substituted heteroaromatic compounds such as a compound of Formula (I): pharmaceutically acceptable salts of the compounds, and pharmaceutical compositions thereof. Also disclosed are methods of treating or preventing cancer using the amino-substituted heteroaromatic compounds, pharmaceutically acceptable salts of the compounds, and pharmaceutical compositions thereof.

Amino-substituted heteroaryls for treating cancers with EGFR mutations

Provided herein are compounds of Formula (A), (B), (C), (D) and (E), pharmaceutically acceptable salts, quaternary amine salts, and N-oxides thereof, and pharmaceutical compositions thereof.  Compounds of Formula (A), (B), (C), (D), and (E) are contemplated useful as therapeutics for treating a wide variety of conditions, e.g., including but not limited to, conditions associated with angiogenesis and with CDK8 and/or CDK19 kinase activity. Further provided are methods of inhibiting CDK8 and/or CDK19 kinase activity, methods of modulating the &#x25a1;-catenin pathway, methods of modulating STAT 1 activity, methods of modulating the TGF&#x3b2;/BMP pathway, methods of modulating HIF-1-alpha activity in a cell, and methods of increasing BIM expression to induce apoptosis, using a compound of Formula (A), (B), (C), (D), or (E). Further provided are CDK8 and CDK19 point mutants and methods of use thereof.

Cortistatin analogues and syntheses and uses thereof

Provided herein are compounds of Formula (A), (B), (C), (D) and (E), pharmaceutically acceptable salts, quaternary amine salts, and N-oxides thereof, and pharmaceutical compositions thereof.  Compounds of Formula (A), (B), (C), (D), and (E) are contemplated useful as therapeutics for treating a wide variety of conditions, e.g., including but not limited to, conditions associated with angiogenesis and with CDK8 and/or CDK19 kinase activity. Further provided are methods of inhibiting CDK8 and/or CDK19 kinase activity, methods of modulating the-catenin pathway, methods of modulating STAT1 activity, methods of modulating the TGF&#x3b2;/BMP pathway, methods of modulating HIF-1-alpha activity in a cell, and methods of increasing BIM expression to induce apoptosis, using a compound of Formula (A), (B), (C), (D), or (E). Further provided are CDK8 and CDK19 point mutants and methods of use thereof.

Compounds of Formula (A'), (B&#x2032;), (C&#x2032;), (D&#x2032;), (E&#x2032;), (A&#x2033;), (B&#x2033;), (C&#x2033;), (D&#x2033;), (E&#x2033;), (G1), and (G2) are useful as therapeutics for treating a wide variety of conditions in a host such as a human, e.g., including but not limited to, conditions associated with angiogenesis and/or which are mediated by CDK8 and/or CDK19 kinase activity. Also provided are methods of modulating the &#x3b2;-catenin pathway, methods of modulating STAT1 activity, methods of modulating the TGF&#x3b2;/BMP pathway, methods of modulating HIF-1-alpha activity in a cell, and methods of increasing BIM expression to induce apoptosis, using an effective amount of a compound of Formula (A&#x2032;), (B&#x2032;), (C&#x2032;), (D&#x2032;), (E&#x2032;), (A&#x2033;), (B&#x2033;), (C&#x2033;), (D&#x2033;), (E&#x2033;), (G1), or (G2).

New cortistatin compounds and pharmaceutically acceptable salts and pharmaceutically acceptable compositions thereof are provided. These compounds can be used to treat a disorder mediated by CDK8 and/or CDK19 kinase or by the Mediator Complex generally. In particular, the compounds can be used, for example, to treat a disorder such as a tumor, cancer, or a disorder associated with angiogenesis.

Cortistatin analogues, syntheses, and uses thereof

The present invention relates to analogs of cortistatin A, J, K, and L, having the general formula: and salts thereof, wherein R, R, R, R, n, and m are as defined herein; processes for preparing such compounds and intermediates thereto; pharmaceutical compositions comprising such compounds; methods for treating a proliferative disease; methods for treating a disease associated with aberrant angiogenesis; methods for inhibiting angiogenesis; and processes for preparing cortistatin A, J, K, and L, and analogs thereof.

Cortistatin analogues and syntheses thereof

Provided herein are compounds of Formula (A), (B), (C), (D) and (E), pharmaceutically acceptable salts, quaternary amine salts, and N-oxides thereof, and pharmaceutical compositions thereof.  Compounds of Formula (A), (B), (C), (D), and (E) are contemplated useful as therapeutics for treating a wide variety of conditions, e.g., including but not limited to, conditions associated with angiogenesis and with CDK8 and/or CDK19 kinase activity. Further provided are methods of inhibiting CDK8 and/or CDK19 kinase activity, methods of modulating the &#x25a1;-catenin pathway, methods of modulating STAT1 activity, methods of modulating the TGF&#x3b2;/BMP pathway, methods of modulating HIF-1-alpha activity in a cell, and methods of increasing BIM expression to induce apoptosis, using a compound of Formula (A), (B), (C), (D), or (E). Further provided are CDK8 and CDK19 point mutants and methods of use thereof.

Provided are a number of compounds structurally related to OSW-1, a natural compound that binds OSBPs. Also provided are pharmaceutical compositions comprising the OSW-1 analogs, as well as methods for use of these OSW-1 analogs, or pharmaceutically acceptable salts, enantiomers, or stereoisomers thereof in the treatment of atherosclerosis. Alzheimer's disease, and cancer, including p21-deficient cancer. Conjugates of OSW-1 analogs with monoclonal antibodies, including monoclonal antibodies targeted to cancer cells, are also provided. Also provided are pharmaceutical compositions comprising the conjugates, as well as methods for use of these conjugates, in the treatment of cancer, including p21-deficient cancer.

OSW-1 analogs and conjugates, and uses thereof

The present invention provides a novel 11-step enantioselective approach to the natural product hyperforin, which enables access to a wide variety of hyperforin analogs. The present invention also provides pharmaceutical compositions comprising inventive hyperforin analogs. Hyperforin analogs synthesized using the present synthetic method are envisioned useful in the treatment of various conditions, including, but not limited to, depression and conditions characterized by depression, inflammatory skin conditions, diabetes, asthma, chronic obstructive pulmonary disease (COPD), kidney disorders, and ischemic brain damage.  

Hyperforin analogs, methods of synthesis, and uses thereof

The present invention provides methods of identifying an agent that modulates PRPK, TPRKB, OSGEP, LAGE3 and its homologs, PRPK/TPRKB complex, and/or KEOPS complex. The present invention also provides compositions of such agents and methods of treating a disease, disorder, or condition associated with PRPK, TPRKB, OSGEP, LAGE3 and its homologs family (CT antigens), PRPK/TPRKB complex, and/or KEOPS complex using such an agent or composition.

PRPK-TPRKB modulators and uses thereof

Growing community of inventors

Lexington, MA, United States of America

Matthew D Shair