Abstract: 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 R1, R2, R3, R4, R5, R6, R7, R8, 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.

Abstract: Described herein are methods for treating ALK5-mediated disease including myelodysplastic syndrome (MDS), anemia and anemia of chronic disease. Also provided are methods of inhibiting ALK5.

Abstract: 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.

Abstract: or a stereoisomer or salt (e.g., pharmaceutically acceptable salt) thereof, wherein R1, R2, R3, R4, R5, 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.

Abstract: 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.

Abstract: 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.

Abstract: Provided herein is a compound of Formula I: or a pharmaceutically acceptable salt thereof, wherein values for the variables (e.g., X1, X2, R2, R3, R4, R5, R6, R7, R8, 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.

Abstract: 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.

Abstract: Methods of treating castration-resistant and castration-sensitive prostate cancer using a compound having the following structure (I): or a pharmaceutically acceptable salt or zwitterionic form thereof, are provided.

Abstract: Provided herein are methods of treating a hematologic cancer in a subject in need thereof, comprising administering to the subject an effective amount of alvocidib, or prodrug thereof, or a pharmaceutically acceptable salt of the foregoing. The subject is in complete remission from the hematologic cancer and measurable residual disease (MRD)-positive following administration of a prior therapy that includes venetoclax, or a pharmaceutically acceptable salt thereof, and does not include alvocidib, or a prodrug thereof, or a pharmaceutically acceptable salt of the foregoing. Other methods are also provided in accordance with other aspects of the invention.

Abstract: Provided herein are methods of treating a hematologic cancer in a subject in need thereof, comprising administering to the subject an effective amount of alvocidib, or prodrug thereof, or a pharmaceutically acceptable salt of the foregoing. The subject is in complete remission from the hematologic cancer and measurable residual disease (MRD)-positive following administration of a prior therapy that does not include alvocidib, or a prodrug thereof, or a pharmaceutically acceptable salt of the foregoing, and is MRD-negative following administration of alvocidib, or a prodrug thereof, or a pharmaceutically acceptable salt of the foregoing. Other methods are also provided in accordance with other aspects of the invention.

Abstract: 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.

Abstract: 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.

Abstract: The present disclosure relates generally to nanoparticle-based imaging, binding, and/or therapy at a targeted anatomical location within a subject. In particular, certain embodiments relate to intraluminal devices and systems configured to apply nanoparticles to an imaging target and/or treatment target within an anatomical lumen and to communicate imaging and/or treatment data wirelessly to one or more external devices.

Abstract: Compounds having the following structure (I): or a stereoisomer, tautomer or pharmaceutically acceptable salt thereof, wherein one of R1, R2 or R3 is —P(?O)(OH)2, and the other two of R1, R2 and R3 are 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.

Abstract: 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.

Abstract: Tartrate salts of the compound of structure (I), (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.

Abstract: 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 R1, R2, R3, and R4 are 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)).

Abstract: This document provides methods for determining biological age of mammalian subjects or assessing whether the subjects are aging normally. Also provided herein are methods for determining whether therapeutic treatment or other interventions for reversing or slowing down aging are effective. This document also provides methods and materials for slowing the progression of biological aging.

Abstract: 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 R1, R2, R3, R4, R5, R6, R7, R8, 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.