Compounds, pharmaceutical compositions, and methods are provided herein that may be used to treat cancer, infectious disease, and other conditions associated with ectonucleotide pyrophosphatase pyrophosphatase-phosphodiesterase (ENPP1) dysfunction.

The invention provides compounds of Formula (I), and their use in methods for treating or preventing a protozoan infection in a subject using a compound of Formula (I). The invention also provides the use of a compound of Formula (I) in the manufacture of a medicament for the treatment of a protozoan infection in a subject. The invention further provides a medical device when used in a method of treating or preventing a protozoan infection in a subject and to a medical device comprising the composition of the invention.

The invention provides compounds of Formula (I), and their use in methods for treating or preventing a protozoan infection in a subject using a compound of Formula (I). The invention also provides the use of a compound of Formula (I) in the manufacture of a medicament for the treatment of a protozoan infection in a subject. The invention further provides a medical device when used in a method of treating or preventing a protozoan infection in a subject and to a medical device comprising the composition of the invention.

The invention provides compounds of Formula (I), and their use in methods for treating or preventing a protozoan infection in a subject using a compound of Formula (I). The invention also provides the use of a compound of Formula (I) in the manufacture of a medicament for the treatment of a protozoan infection in a subject. The invention further provides a medical device when used in a method of treating or preventing a protozoan infection in a subject and to a medical device comprising the composition of the invention.

The present disclosure relates to prodrugs, double prodrugs, derivatives and analogues of 3-(methylamino)-2-((methylamino)methyl)propane-1-thiol. The compounds of this disclosure also relate to ##STR00001##
The use of these compounds as radio— and chemo—protectors is also described.

Methods and compositions for treating leukemia are disclosed. Acylated 6-aminoindoles, acylated 6-aminopyrrolopyridines and acylated 3-aminopyrrolo[3,2-c]pyridazines of the following formula

##STR00001##

inhibit ENL/AF9 YEATS and are therefore useful for treating leukemia.

Methods and compositions for treating leukemia are disclosed. Acylated 6-aminoindoles, acylated 6-aminopyrrolopyridines and acylated 3-aminopyrrolo[3,2-c]pyridazines of the following formula

##STR00001##

inhibit ENL/AF9 YEATS and are therefore useful for treating leukemia.

The invention is in the field of molecular diagnosis of medical diseases and their treatment. More in particular, it provides methods and means for detecting hypertension, more in particular essential primary hypertension, even more in particular NOX5-dependent hypertension. The invention also provides methods for the treatment of hypertension, in particular essential primary hypertension, more in particular NOX5-dependent hypertension. The invention also provides theragnostics, wherein therapy is combined with diagnosis, more in particular wherein the level of NOX5 is determined in a sample from a subject and wherein the subject is treated with NOX5 inhibitors or compounds that decrease the levels of NOX5 if the NOX5 levels are above a certain threshold value. Further, the invention also provides theragnostics, wherein diagnosis is combined with therapy, more in particular wherein the (plasma) level of NOX5 is determined in a sample from a subject and wherein the subject is treated with NOX5 inhibitors or compounds that reverse the result of NOX5 activity in the subject, when the determined NOX5 level is exceeding a predetermined threshold level. Finally, the invention relates to an animal model suitable for developing diagnostic methods and therapeutic treatments for NOX5-dependent hypertension.

Provided are methods and compositions for the treatment of cancer. The methods comprise administering to an individual in need of treatment inhibitors of WHSC1 expression, function or activity in combination with PARP inhibitors or immune based therapy. In an aspect, the present disclosure provides compositions comprising one or more WHSC1 inhibitors and one or more PARP inhibitors, or one or more WHSC1 inhibitors and one or more immune checkpoint inhibitors.

Provided are methods and compositions for the treatment of cancer. The methods comprise administering to an individual in need of treatment inhibitors of WHSC1 expression, function or activity in combination with PARP inhibitors or immune based therapy. In an aspect, the present disclosure provides compositions comprising one or more WHSC1 inhibitors and one or more PARP inhibitors, or one or more WHSC1 inhibitors and one or more immune checkpoint inhibitors.