Whitehead Institute for Biomedical Research

Syros Pharmaceuticals, Inc.

Fulcrum Therapeutics, Inc.

Dana-Farber-Cancer Institute Inc.

Peter B Rahl

Jason J Marineau

Richard A Young

Stephane Ciblat

Yi Zhang

Ivan Viktorovich Efremov

Kevin Sprott

Robin Larouche-Gauthier

Francis Beaumier

Luce Lépissier

Qingyi Li

Owen Brendan Wallace

Lorin A Thompson, Iii

Boubacar Sow

Lauren Berstler

Christopher Roberts

Feng Zhou

Shawn Donald Johnstone

Steven Kazmirski

James Elliott Bradner

Jun Qi

Michael Robert McKeown

Matthew G Guenther

Michael R Mckeown

The invention relates to modulators of Embryonic Ectoderm Development (EED) and/or Polycomb Repressive Complex 2 (PRC2) useful in the treatment of disorders and diseases associated with EEC and PRC2, being macrocyclic azolopyridine derivatives and compositions thereof of Formula I: or a pharmaceutically acceptable salt, prodrug, solvate, hydrate, enantiomer, isomer, or tautomer thereof, wherein X, X, X, A, A, Y, R, R, R, and Rare as described herein.

Macrocyclic azolopyridine derivatives as EED and PRC2 modulators

The present invention provides novel compounds of Formulas (I) and (II) and pharmaceutically acceptable salts, solvates, hydrates, tautomers, stereoisomers, isotopically labeled derivatives, and compositions thereof. Also provided are methods and kits involving the compounds or compositions for treating or preventing proliferative diseases, e.g., cancers (e.g., breast cancer, prostate cancer, lymphoma, lung cancer, pancreatic cancer, ovarian cancer, neuroblastoma, or colorectal cancer), benign neoplasms, angio genesis, inflammatory diseases, fibrosis (e.g., polycystic kidney disease), autoinflammatory diseases, and autoimmune diseases in a subject.

Compounds for the modulation of Myc activity

The present invention provides novel compounds of Formulas (I) and (II) and pharmaceutically acceptable salts, solvates, hydrates, tautomers, stereoisomers, isotopically labeled derivatives, and compositions thereof. Also provided are methods and kits involving the compounds or compositions for treating or preventing proliferative diseases, e.g., cancers (e.g., breast cancer, prostate cancer, lymphoma, lung cancer, pancreatic cancer, ovarian cancer, neuroblastoma, or colorectal cancer), benign neoplasms, angio genesis, inflammatory diseases, fibrosis (e.g., polycystic kidney disease), autoinflammatory diseases, and autoimmune diseases in a subject. 

The present invention provides novel compounds of Formula (I) and Formula (II) and pharmaceutically acceptable salts, solvates, hydrates, tautomers, stereoisomers, isotopically labeled derivatives, and compositions thereof. Also provided are methods and kits involving the compounds or compositions for treating or preventing proliferative diseases, e.g., cancers (e.g., breast cancer, prostate cancer, lymphoma, lung cancer, pancreatic cancer, ovarian cancer, neuroblastoma, or colorectal cancer), benign neoplasms, angio genesis, inflammatory diseases, fibrosis (e.g., polycystic kidney disease), autoinflammatory diseases, and autoimmune diseases in a subject. 

Compounds for the modulation of myc activity

Disclosed herein are methods and compositions useful for inhibiting interaction between a bromodomain protein and an immunoglobulin (Ig) regulatory element. The methods and compositions are particularly useful for downregulating expression of an oncogene translocated with an Ig locus, as well as for treating a cancer (e.g., hematological malignancy) characterized by increased expression of an oncogene which is translocated with an Ig locus. Also disclosed herein are methods and assays for identifying agents that interfere with binding of bromodomain proteins to Ig regulatory elements, as well as methods and assays for identifying inhibitors of bromodomain.

Method for identifying bromodomain inhibitors

The present invention provides compounds of Formula (I-A), (I-B), and (I-C), pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof. Compounds of the present invention are useful for inhibiting Myc (e.g., c-Myc) activity. The present invention further provides methods of using the compounds described herein for treating Myc-mediated disorders (e.g., cancer and other proliferative diseases). The present invention also provides assays for identifying Myc inhibitors. 

Pyrrol-1-yl benzoic acid derivatives useful as myc inhibitors

In some aspects, the invention provides compositions and methods of use for treating a variety of diseases. In some aspect, the compositions and methods involve combined modulation of transcriptional modulators.

Combination methods for treatment of disease

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Natick, MA, United States of America

Peter B Rahl