Harvard College

Nuvalent, Inc.

Other

Taiho Pharmaceutical Company Limited

Henry Efrem Pelish

Matthew D Shair

Scot Richard Mente

Joshua Courtney Horan

Anupong Tangpeerachaikul

Xinxing Tang

Juergen Ramharter

Brian Bor-Jen Liau

Jae Young Ahn

Randall W King

Baudouin Gerard

Alexander Arefolov

Nicholas Westwood

Eun Sun Park

Kristin Lynne Andrews

Astrid S Clarke

Yuting Sun

Grace L Williams

Maria Paola Castaldi

Jennifer E Ring

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

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.

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

The present invention provides novel alkaloid compounds and collections of these compounds, and provides methods for the synthesis of these compounds using biomimetic synthetic strategies. Additionally, the present invention provides pharmaceutical compositions and methods for treating disorders such as bacterial infections, proliferative diseases, and reproductive disorders, to name a few.

Growing community of inventors

Newton, MA, United States of America

Henry Efrem Pelish