Provided herein are compositions and methods to that target microbial proteases to ameliorate the intestinal barrier dysfunction and restore mucosal integrity. They are useful to treat and prevent diseases and disorders caused by pathogenic bacteria in the gastrointestinal system of a subject.

Disclosed are synergistic compositions comprising a therapeutically effective synergistic amount of a protein kinase B (Akt) activation inhibitor and a second inhibitor selected from a checkpoint (CHK1) inhibitor, a multitargeted histone deacetylase/human epidermal growth factor receptor (HDAC/Her1/2) inhibitor, a phosphoinositide 3-kinase (PI3K) inhibitor, or a combination thereof. Methods of using the disclosed compositions for treating, preventing, reducing, and/or inhibiting a cancer comprising administering the same to a subject are also disclosed.

Disclosed are synergistic compositions comprising a therapeutically effective synergistic amount of a protein kinase B (Akt) activation inhibitor and a second inhibitor selected from a checkpoint (CHK1) inhibitor, a multitargeted histone deacetylase/human epidermal growth factor receptor (HDAC/Her1/2) inhibitor, a phosphoinositide 3-kinase (PI3K) inhibitor, or a combination thereof. Methods of using the disclosed compositions for treating, preventing, reducing, and/or inhibiting a cancer comprising administering the same to a subject are also disclosed.

Disclosed are synergistic compositions comprising a therapeutically effective synergistic amount of a protein kinase B (Akt) activation inhibitor and a second inhibitor selected from a checkpoint (CHK1) inhibitor, a multitargeted histone deacetylase/human epidermal growth factor receptor (HDAC/Her1/2) inhibitor, a phosphoinositide 3-kinase (PI3K) inhibitor, or a combination thereof. Methods of using the disclosed compositions for treating, preventing, reducing, and/or inhibiting a cancer comprising administering the same to a subject are also disclosed.

The present invention relates to compounds that are modulators of Integrin Linked Kinase (ILK), and methods of treating diseases with such compounds. In certain embodiments, the compounds are within Formulas I-VII (e.g., Csbl-1). In some embodiments, the compounds are used to treat an ILK-mediated disease, such as cancer (e.g., triple negative breast cancer) or an inflammatory disease.

Compounds of formulae (I) and (II), compositions, and methods for use in inhibiting the E3 enzyme Cbl-b in the ubiquitin proteasome pathway are disclosed. The compounds, compositions, and methods can be used to modulate the immune system, to treat diseases amenable to immune system modulation, and for treatment of cells in vivo, in vitro, or ex vivo.

##STR00001##

Compounds of formulae (I) and (II), compositions, and methods for use in inhibiting the E3 enzyme Cbl-b in the ubiquitin proteasome pathway are disclosed. The compounds, compositions, and methods can be used to modulate the immune system, to treat diseases amenable to immune system modulation, and for treatment of cells in vivo, in vitro, or ex vivo.

##STR00001##

The present disclosure relates generally to methods of making immune effector cells, such as those engineered to express a Chimeric Antigen Receptor (CAR) including CAR-T cells, and compositions comprising the same, for use in treating cancer.

The present disclosure relates generally to methods of making immune effector cells, such as those engineered to express a Chimeric Antigen Receptor (CAR) including CAR-T cells, and compositions comprising the same, for use in treating cancer.

The present invention provides use of a multi-target protein kinase inhibitor compound A or a pharmaceutically acceptable salt thereof in the manufacture of a medicament for treating leukemia, and provides a method for treating acute myeloid leukemia, especially acute myeloid leukemia with FLT3 mutation, with compound A. In clinical trials, compound A has certain efficacies both on acute myeloid leukemia with FLT3-ITD mutation and/or FLT3-TKD mutation, and on DEK-CAN positive acute myeloid leukemia with FLT3-ITD mutation. Patients with relapsed and/or refractory acute myeloid leukemia who have failed treatment previously with Type II FLT3 inhibitors (e.g., sorafenib) can still clinically benefit from the treatment with compound A.

##STR00001##