Tolero Pharmaceuticals, Inc.

University of Utah Research Foundation

The University of Arizona

Supergen, Inc

Sumitomo Pharma Oncology, Inc.

Neuropro Technologies, Inc.

Sumitomo Dainippon Pharma Oncology, Inc.

Montigen Pharmaceuticals, Inc.

Other

Astex Pharmaceuticals, Inc.

Astex Pharmaceutials, Inc.

Biolexis Therapeutics, Inc.

David J Bearss

Steven L Warner

Hariprasad Vankayalapati

Adam Siddiqui-Jain

Sunil Sharma

Venkataswamy Sorna

Clifford J Whatcott

Laurence H Hurley

Daruka Mahadevan

Sridevi Bashyam

Yong Xu

Benjamin J Remington

Pasit Phiasivongsa

Sanjeev Redkar

Xiao-Hui Liu

Kavian Shahi

Bret Stephens

Jason Marc Foulks

Alexis Mollard

Lars Mouritsen

Peter W Peterson

Wontak Kim

Gary A Flynn

William Alexander Denny

Rajashree Joshi-Hangal

Paul Flynn

Swarna Gamage

Darby Brooke

James Welsh

Vincent A Fischetti

Jeyaprakashnarayanan Seenisamy

Yuka Arikawa

Hiroki Umehara

Krzysztof Swierczek

Yuji Fujiwara

Akihito Nonoyama

Akihito Kiguchiya

Zhaoliang Li

Charles Erec Stabbins

Dongqing Yan

Kyle Medley

Stephen Patrick Anthony

Michael Vincent McCullar

Susan Carol Smith

Ken Fujimura

Nozomi Tomimatsu

Steve L Warner

Compounds having the following structure (I):

Alvocidib prodrugs having increased bioavailability

or a stereoisomer or salt (e.g., pharmaceutically acceptable salt) thereof, wherein R, R, R, R, R, p, m, and n are as defined herein. Use of the compounds as a component of a pharmaceutical compositions and methods for their use are also provided.

CDK9 inhibitors

Provided herein are various regimens for treating acute myeloid leukemia (AML) in subjects (e.g, patients) who have undergone one or more prior anti-AML therapies involving venetoclax, and have shown disease progression after the one or more prior therapies. The treatment regimens disclosed herein involve alvocidib, either as a monotherapy, or in combination with cytarabine or a hypomethylating agent, such as decitabine or azacitidine. The treatment regimens disclosed herein do not involve combination therapy of alvocidib with venetoclax.

Treatment of acute myeloid leukemia (AML) with venetoclax failure

A compound of Structure (I): or a pharmaceutically acceptable salt thereof, alone or in combination with a second therapeutic agent, as well as methods of treating a PKM2-mediated disease or disorder using the same are provided herein.

Compositions comprising PKM2 modulators and methods of treatment using the same

Provided herein is a compound of Formula I: or a pharmaceutically acceptable salt thereof, wherein values for the variables (e.g., X, X, R, R, R, R, R, R, R, m, n) are as described herein. Compounds of Formula I, pharmaceutically acceptable salts thereof, pharmaceutical compositions of either of the foregoing, and combinations of any of the foregoing can be used to treat tyrosine kinase non-receptor 1 (TNK1)-mediated diseases, disorders and conditions.

Tyrosine kinase non-receptor 1 (TNK1) inhibitors and uses thereof

Methods for treating BCL-2 inhibitor-resistant cancer in subjects using an MCL-1 inhibitor as well as compositions associated with the same are disclosed.

Treatment regimen for cancers that are insensitive to BCL-2 inhibitors using the MCL-1 inhibitor alvocidib

Tartrate salts of the compound of structure (I), crystalline forms thereof, and therapeutic applications thereof for treating solid tumors (e.g., advanced solid tumor) or hematopoietic cancers. Also provided herein are methods for synthesizing the tartrate salts and the crystalline forms thereof.

AXL kinase inhibitors and use of the same

Methods for treating a disease in a subject in need thereof by administering an ACVR1 inhibitor having the following formula (I) are disclosed: including stereoisomers, tautomers, pharmaceutically acceptable salts and prodrugs thereof, wherein R, R, R, and Rare as defined herein. Subjects that may benefit from treatment may have mutations in their ACVR1 gene. Various diseases may be treated using the described methods, including cancers (e.g., diffuse intrinsic pontine glioma (DIPG)) and genetic disorders (e.g., fibrodysplasia ossificans progressiva (FOP)).

Methods for treating diseases associated with abnormal ACVR1 expression and ACVR1 inhibitors for use in the same

Combination therapies for treatment of cancer are provided. The disclosed methods comprise administration of a cyclin-dependent kinase inhibitor and a DNA methyltransferase inhibitor to a mammal in need thereof.

Combination therapies for treatment of cancer

Compounds having activity as inhibitors of ALK2 kinase and/or JAK2 kinase are disclosed. The compounds have the following structure (I): including stereoisomers, tautomers, pharmaceutically acceptable salts and prodrugs thereof, wherein R, R, R, R, R, R, R, R, X, z and A are as defined herein. Methods associated with preparation and use of such compounds, as well as pharmaceutical compositions comprising such compounds, are also disclosed.

JAK1 and ALK2 inhibitors and methods for their use

The present disclosure provides diagnostic methods useful for predicting a patient's response to alvocidib and guiding a physician decision to administer alvocidib to the patient.

Predicting response to alvocidib by mitochondrial profiling

Compounds having the following structure (I): or a stereoisomer, tautomer or pharmaceutically acceptable salt thereof, wherein one of R, Ror Ris &#x2014;P(&#x2550;O)(OH), and the other two of R, Rand Rare each H, are provided. Pharmaceutical compositions comprising the compounds, and methods for use of the compounds for treating diseases associated with overexpression of a cyclin-dependent kinase (CDK) are also provided.

The present disclosure is generally directed to profiling peptides, compositions, and kits, as well as methods of use thereof. The profiling peptides comprise an Mcl-1 binding domain, and optionally a cellular uptake moiety. The methods of using such profiling peptides include predicting sensitivity of a cancer, selecting a treatment, treating a cancer, producing a sensitivity profile, and the like.

Profiling peptides and methods for sensitivity profiling

Growing community of inventors

Alpine, UT, United States of America

David J Bearss