The present invention relates to stable liquid pharmaceutical formulations of cyclophosphamide comprising cyclophosphamide and at least one pharmaceutically acceptable excipient wherein moisture content of the liquid formulation is less than about 2.0% by weight. The invention further relates to stable liquid formulations of cyclophosphamide prepared by a process comprising a step of reducing the moisture content from cyclophosphamide or liquid compositions of cyclophosphamide or both. The invention further relate to method of using such stable liquid formulations of cyclophosphamide for parenteral administration either as ready-to-use or ready-to-dilute for treating various cancer disorders.

It has been discovered that the cyclic peptide EnnA inactivates the Hsp90 chaperone pathway, but without activating an extensive heat shock response and overexpression of anti-apoptotic proteins. Mechanistically distinct, EnnA inhibits Hsp90 and destabilize PDL-1 and IDO, two major immune checkpoints mediating tumor-induced immune suppression. The provided herein show that EnnA profoundly modulates the cytokine signature of cancer cells and promotes a cytokine profile that favors an immune attack on tumor cells. This translates into highly efficacious anti-tumor activity in vivo, which, when combined with a single dose of chemotherapy, completely reduced the tumor burden in experimental animals and instilled highly efficient immune memory against the primary tumor.

It has been discovered that the cyclic peptide EnnA inactivates the Hsp90 chaperone pathway, but without activating an extensive heat shock response and overexpression of anti-apoptotic proteins. Mechanistically distinct, EnnA inhibits Hsp90 and destabilize PDL-1 and IDO, two major immune checkpoints mediating tumor-induced immune suppression. The provided herein show that EnnA profoundly modulates the cytokine signature of cancer cells and promotes a cytokine profile that favors an immune attack on tumor cells. This translates into highly efficacious anti-tumor activity in vivo, which, when combined with a single dose of chemotherapy, completely reduced the tumor burden in experimental animals and instilled highly efficient immune memory against the primary tumor.

The present invention provides prodrugs and methods of use thereof.

Disclosed herein are methods for treating a cancer comprising: a. administering a Btk inhibitor to a subject sufficient to result in an increase or appearance in the blood of a subpopulation of lymphocytes defined by immunophenotyping; b. determining the expression profile of one or more biomarkers from one or more subpopulation of lymphocytes; and c. administering a second agent based on the determined expression profile.

Disclosed herein are methods for treating a cancer comprising: a. administering a Btk inhibitor to a subject sufficient to result in an increase or appearance in the blood of a subpopulation of lymphocytes defined by immunophenotyping; b. determining the expression profile of one or more biomarkers from one or more subpopulation of lymphocytes; and c. administering a second agent based on the determined expression profile.

The present invention relates to stable liquid pharmaceutical formulations of cyclophosphamide comprising cyclophosphamide and at least one pharmaceutically acceptable excipient wherein moisture content of the liquid formulation is less than about 2.0% by weight. The invention further relates to stable liquid formulations of cyclophosphamide prepared by a process comprising a step of reducing the moisture content from cyclophosphamide or liquid compositions of cyclophosphamide or both. The invention further relate to method of using such stable liquid formulations of cyclophosphamide for parenteral administration either as ready-to-use or ready-to-dilute for treating various cancer disorders.

The present invention relates to stable liquid pharmaceutical formulations of cyclophosphamide comprising cyclophosphamide and at least one pharmaceutically acceptable excipient wherein moisture content of the liquid formulation is less than about 2.0% by weight. The invention further relates to stable liquid formulations of cyclophosphamide prepared by a process comprising a step of reducing the moisture content from cyclophosphamide or liquid compositions of cyclophosphamide or both. The invention further relate to method of using such stable liquid formulations of cyclophosphamide for parenteral administration either as ready-to-use or ready-to-dilute for treating various cancer disorders.

Described are compounds that act as AKR1C3 inhibitors or pharmaceutically acceptable salts or solvates or isotopically substituted compounds thereof and methods thereof.

The present invention provides methods for detecting and/or treating a subject having an aneurysm or at risk for developing an aneurysm. It has been discovered that a key metabolite of the kynurenine (Kyn) pathway, a major route for the metabolism of essential amino acid tryptophan (Trp) into nicotinamide adenine dinucleotide (NAD+), plays a critical role in the formation of aneurysms, for example abdominal aortic aneurysms. In particular, it has been discovered that 3-Hydroxyanthranilic acid (3-HAA), a product of kynureninase (KYNU), plays a causative role in the formation of aneurysms by, for example exerting pro-inflammatory effects on vascular smooth muscle cells. It has further been discovered that elevated levels of 3-HAA are indicative of the presence and/or progression of an aneurysm, and 3-HAA levels correlate with the size (aortic diameter) of the aneurysm.