The present disclosure relates to compositions and methods of carbonic anhydrase IX inhibitors. The present disclosure also relates to targeting conjugates of carbonic anhydrase IX inhibitors. The present disclosure also relates to the use of targeting conjugates of carbonic anhydrase IX inhibitors in methods of treating disease and for imaging of disease.

The present invention relates to a composition for preventing or treating diabetes mellitus using a 4-component mixture of putrescine, glucosamine, nicotinamide, and a STAT3 inhibitor. It has been confirmed that blood glucose is stably regulated when a compound of the 4-component mixture according to the present invention is injected into the caudal vein of a diabetes mellitus-induced mouse. The compound can be practically and usefully used as a therapeutic agent for diabetes mellitus patients and patients exposed to diabetes mellitus risk.

The present invention relates to a composition for preventing or treating diabetes mellitus using a 4-component mixture of putrescine, glucosamine, nicotinamide, and a STAT3 inhibitor. It has been confirmed that blood glucose is stably regulated when a compound of the 4-component mixture according to the present invention is injected into the caudal vein of a diabetes mellitus-induced mouse. The compound can be practically and usefully used as a therapeutic agent for diabetes mellitus patients and patients exposed to diabetes mellitus risk.

Described herein are protein-payload conjugates and compositions thereof that are useful, for example, for target-specific delivery of therapeutic and/or imaging agent moieties. In certain embodiments, provided are specific and efficient methods for producing protein-payload constructs (e.g., antibody-drug conjugates) utilizing a combination of transglutaminase and Diels-Alder techniques. Antibody-drug conjugates and compositions which comprise glutaminyl-modified antibodies, Diels-Alder adducts, and reactive payloads and are provided.

Described herein are protein-payload conjugates and compositions thereof that are useful, for example, for target-specific delivery of therapeutic and/or imaging agent moieties. In certain embodiments, provided are specific and efficient methods for producing protein-payload constructs (e.g., antibody-drug conjugates) utilizing a combination of transglutaminase and Diels-Alder techniques. Antibody-drug conjugates and compositions which comprise glutaminyl-modified antibodies, Diels-Alder adducts, and reactive payloads and are provided.

Embodiments of the disclosure provide methods and compositions that facilitate cancer treatment including at least because they concern therapies that circumvent the tumor microenvironment. In specific embodiments, compositions are utilized for therapy that utilize NK cells that are protected from the direct inhibition of their activity (using TGF-beta inhibitors) and/or that are indirectly protected from TGF-beta (using integrin inhibitors). In specific embodiments, the NK cells have deficient expression and/or activity for TGF-beta Receptor 2 and/or glucocorticoid receptor.

Embodiments of the disclosure provide methods and compositions that facilitate cancer treatment including at least because they concern therapies that circumvent the tumor microenvironment. In specific embodiments, compositions are utilized for therapy that utilize NK cells that are protected from the direct inhibition of their activity (using TGF-beta inhibitors) and/or that are indirectly protected from TGF-beta (using integrin inhibitors). In specific embodiments, the NK cells have deficient expression and/or activity for TGF-beta Receptor 2 and/or glucocorticoid receptor.

The present invention relates to pharmaceutical compositions of 1,2,4-oxadiazole compounds or a pharmaceutically acceptable salt thereof of formula (I) ##STR00001## In the formula Q is O, R.sub.1 is the side chain of Ser, R.sub.2 is —CO-Thr, R.sub.3 is the side chain of Asn or Glu, and R.sub.4, R.sub.5 and R.sub.6 are each H.

The present invention relates to pharmaceutical compositions of 1,2,4-oxadiazole compounds or a pharmaceutically acceptable salt thereof of formula (I) ##STR00001## In the formula Q is O, R.sub.1 is the side chain of Ser, R.sub.2 is —CO-Thr, R.sub.3 is the side chain of Asn or Glu, and R.sub.4, R.sub.5 and R.sub.6 are each H.

The present invention relates to seco (opened ring) macrolide compounds, to the process for preparation thereof, to the use of said seco macrolide compounds as intermediates for preparation of macrolide based macrocycles, to macrolide based macrocycles obtained from said seco macrolide compounds, to the process for preparation of macrolide based macrocycles, to the pharmaceutical compositions comprising macrolide based macrocycles, and to the use of macrolide based macrocycles as therapeutic agents.