The present invention relates to prodrugs of vascular disrupting agents comprising a vascular disrupting agent (VDA) associated with a MMP proteolytic cleavage site and to the use of such prodrugs in the targeted treatment of cancer.

The present disclosure relates to steroidal glucocorticoid receptor (GR) ligands and related compositions that degrade the GR and/or modulate its activity that may be utilized as pharmaceuticals for the treatment of diseases including cancer.

Provided herein are small molecules comprising a first domain that binds to ASH1L and a second domain that facilitates ASH1L degradation. In particular, ASH1L-targeting proteolysis targeting chimeras (PROTACs) and methods of use thereof for the treatment of disease (e.g., acute leukemia, solid cancers and other diseases dependent on activity of ASH1L) are provided.

Provided herein are small molecules that bind to ASH1L and inhibit ASH1L activity, and methods of use thereof for the treatment of disease, including acute leukemia, solid cancers and other diseases dependent on activity of ASH1L.

A method, composition, and kit for treating a malarial infection in a subject by using an enzyme conjugate comprising a variant cystathione-gamma-lyase and a targeting ligand which binds to erythrocytes infected with Plasmodium pathogens. The variant cystathione-gamma-lyase has methioninase activity. Also disclosed is a method of treating Plasmodium-infected blood by exposing the infected blood with the enzyme conjugate.

Provided herein are compounds, which act as protein degradation inducing moieties for aurora kinase (AURK). The present application also relates to methods for the targeted degradation of AURK through the use of the compounds that link a ubiquitin ligase-binding moiety to a ligand that is capable of binding to AURK which can be utilized in the treatment of disorders modulated by AURK.

The present application provides bifunctional compounds of Formula (I): ##STR00001##
or Targeting Ligand
or an enantiomer, diastereomer, or stereoisomer thereof, or pharmaceutically acceptable salt, hydrate, solvate, or prodrug thereof, which act as protein degradation inducing moieties for bromodomain-containing protein 9 (BRD9). The present application also provides methods for the targeted degradation of BRD9 through the use of the bifunctional compounds that link a ubiquitin ligase-binding moiety to a ligand that is capable of binding to BRD9 which can be utilized in the treatment of disorders modulated by BRD9.

Provided herein are small molecules that bind to ASH1L and inhibit ASH1L activity, and methods of use thereof for the treatment of disease, including acute leukemia, solid cancers and other diseases dependent on activity of ASH1L.

Provided herein are small molecules comprising a first domain that binds to ASH1L and a second domain that facilitates ASH1L degradation. In particular, ASH1L-targeting proteolysis targeting chimeras (PROTACs) and methods of use thereof for the treatment of disease (e.g., acute leukemia, solid cancers and other diseases dependent on activity of ASH1L) are provided.

Provided herein are small molecules that bind to ASH1L and inhibit ASH1L activity, and methods of use thereof for the treatment of disease, including acute leukemia, solid cancers and other diseases dependent on activity of ASH1L.