Syros Pharmaceuticals, Inc.

Dana-Farber-Cancer Institute Inc.

Other

Zipwhip, Inc.

Michael Bradley

Stephane Ciblat

Jason J Marineau

Anzhelika Kabro

M Arshad Siddiqui

Kevin Sprott

Darby Schmidt

Melissa Leblanc

Stephanie Roy

Dana K Winter

Tom Miller

Serge Leger

Nathanael Schiander Gray

Tinghu Zhang

Dansu Li

Amy Ripka

Joel D Moore

Claudio Edmundo Chuaqui

Nathanael S Gray

James Lapic

Alan Capps

Patrick Deroy

Kenneth Matthew Whitmore

Kate-Lyn Lund

Henri Piras

The present invention provides various compositions, including compounds of Formula (I) or (Ia), or a species thereof, and pharmaceutically acceptable salts, solvates (e.g., hydrates), stereoisomer, tautomers, isotopic and other specified forms thereof. Also provided are methods (or uses) and kits involving the compounds or pharmaceutically acceptable compositions containing them for treating or preventing a disease (e.g., a proliferative disease such as cancer) in a subject. Administration of a compound or pharmaceutical composition described herein is expected to inhibit cyclin-dependent kinase 7 (CDK7), and thereby, induce apoptosis in tumor cells in the subject.

Inhibitors of cyclin-dependent kinase 7 (CDK7)

The present invention provides, inter alia, compounds having the structures of formulas described herein; pharmaceutically acceptable salts, solvates, hydrates, tautomers, and isotopic forms thereof; and compositions (e.g., pharmaceutical compositions and kits) containing one or more of the foregoing. Also provided are methods of administering and uses involving the compounds and/or pharmaceutical compositions for treating or preventing disease. The disease can be a proliferative disease, such as a cancer (e.g., a blood cancer (e.g., a leukemia or lymphoma), a brain cancer, a breast cancer, melanoma, multiple myeloma, or an ovarian cancer) a benign neoplasm, pathologic angiogenesis, or a fibrotic disease. While no aspect of the invention is limited by the biological events that may transpire, administering a compound or other composition described herein may selectively inhibit the aberrant expression or activity of cyclin-dependent kinase 7 (CDK7) and, thereby, induce cellular apoptosis and/or inhibit the transcription of disease-related genes in the patient (or in a biological sample).

Inhibitors of cyclin dependent kinase 7 (CDK7)

The present invention provides novel compounds of Formula (I), 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., leukemia, melanoma, multiple myeloma), benign neoplasms, angiogenesis, inflammatory diseases, autoinflammatory diseases, and autoimmune diseases) in a subject. Treatment of a subject with a proliferative disease using a compound or composition of the invention may inhibit the aberrant activity of a kinase, such as a cyclin-dependent kinase (CDK) (e.g., cyclin-dependent kinase 7 (CDK7)), and therefore, induce cellular apoptosis and/or inhibit transcription in the subject. 

Heteroaromatic compounds useful for the treatment of proliferative diseases

The present invention provides novel compounds of Formula (I), and pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled derivatives, prodrugs, and compositions thereof. Also provided are methods and kits involving the inventive compounds or compositions for treating or preventing proliferative diseases (e.g., cancers (e.g., leukemia, lymphoma, melanoma, multiple myeloma, breast cancer, Ewing's sarcoma, osteosarcoma, brain cancer, neuroblastoma, lung cancer), benign neoplasms, angiogenesis, inflammatory diseases, autoinflammatory diseases, and autoimmune diseases) in a subject. Treatment of a subject with a proliferative disease using a compound or composition of the invention may inhibit the aberrant activity of a kinase, such as a cyclin-dependent kinase (CDK) (e.g., cyclin-dependent kinase 7 (CDK7), cyclin-dependent kinase 12 (CDK12), or cyclin-dependent kinase 13 (CDK13)), and therefore, induce cellular apoptosis and/or inhibit transcription in the subject. 

Polycyclic inhibitors of cyclin-dependent kinase 7 (CDK7)

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., leukemia, melanoma, multiple myeloma), benign neoplasms, angiogenesis, inflammatory diseases, autoinflammatory diseases, and autoimmune diseases) in a subject. Treatment of a subject with a proliferative disease using a compound or composition of the invention may inhibit the aberrant activity of cyclin-dependent kinase 7 (CDK7), and therefore, induce cellular apoptosis and/or inhibit transcription in the subject.

A system and method dynamically generates structured graphical user interfaces based on the type of device accessing a user interface. The system and method dynamically trigger the pre-population of content within a native application or internet-based application on user agent information and user-entered information and initiates SMS communications between users of disparate device types.

Activation of SMS signaling from dynamically activated control interface

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., leukemia, melanoma, multiple myeloma), benign neoplasms, angiogenesis, inflammatory diseases, autoinflammatory diseases, and autoimmune diseases) in a subject. Treatment of a subject with a proliferative disease using a compound or composition of the invention may inhibit the aberrant activity of cyclin-dependent kinase 7 (CDK7), and therefore, induce cellular apoptosis and/or inhibit transcription in the subject. 

T post support step

Multiple position swing up jump rail support

A spring tension arrow stabilizing mechanism is provided with trigger-controlled disengagement. The arrow stabilizing mechanism includes a mounting bracket for attachment to a bow, an elongate rod rotatably mounted through the mounting bracket so as to have a forward end and a rearward end, a holding mechanism mounted on the rearward end of the rod, and a trigger mechanism pivotally mounted to the mounting bracket and attached to the forward end of the rod. The trigger mechanism has an at rest position and a pulled position. The holding mechanism has an engaged and a disengaged position, with the engaged position for stabilizing an arrow on the bow. A tension element biases the trigger mechanism into the at rest position and the holding mechanism into the engaged position. Pivoting of the trigger mechanism to the pulled position causes rotation of the elongate rod and thus the holding mechanism mounted thereon to the disengaged position.

Arrow stabilizing mechanism for bow and arrow

Growing community of inventors

Allston, MA, United States of America

Michael Bradley