Compounds, 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.

Compounds, 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.

The invention provides formulations containing highly concentrated solutions of rifabutin and methods of making such formulations. The invention also provides methods of using such formulations to treat a bacterial infection in a subject.

The invention provides formulations containing highly concentrated solutions of rifabutin and methods of making such formulations. The invention also provides methods of using such formulations to treat a bacterial infection in a subject.

Materials and methods for regulating lipid abundance by modulating Protease Activated Receptor 1 (PAR1) and Protease Activated Receptor 2 (PAR2) levels arc provided herein. In a first aspect, this document features a method that includes (a) identifying a mammal as having a condition characterized at least by impaired lipid production, impaired cholesterol production, or both impaired lipid production and impaired cholesterol production; and (b) administering to the mammal an inhibitor of PAR1 and/or PAR2 in an amount effective to increase lipid production and/or cholesterol production in the mammal.

Materials and methods for regulating lipid abundance by modulating Protease Activated Receptor 1 (PAR1) and Protease Activated Receptor 2 (PAR2) levels arc provided herein. In a first aspect, this document features a method that includes (a) identifying a mammal as having a condition characterized at least by impaired lipid production, impaired cholesterol production, or both impaired lipid production and impaired cholesterol production; and (b) administering to the mammal an inhibitor of PAR1 and/or PAR2 in an amount effective to increase lipid production and/or cholesterol production in the mammal.

Provided herein are combination-potentiator (“co-potentiator”) therapeutic regimens, which can be used to modulate cystic fibrosis transmembrane conductance regulator (CTFR) mutant proteins. Co-potentiators have potential utility for treatment of many loss-of-function mutations of the CFTR chloride channel (e.g., N1303K).

Provided herein are combination-potentiator (“co-potentiator”) therapeutic regimens, which can be used to modulate cystic fibrosis transmembrane conductance regulator (CTFR) mutant proteins. Co-potentiators have potential utility for treatment of many loss-of-function mutations of the CFTR chloride channel (e.g., N1303K).

Pyrano[4,3-b]indole derivatives as alpha-1-antitrypsin modulators for treating alpha-1-antitrypsin deficiency (AATD)

Pyrano[4,3-b]indole derivatives as alpha-1-antitrypsin modulators for treating alpha-1-antitrypsin deficiency (AATD)