Glutamine antagonists and their use for treating oncological, immunological, and neurological diseases are disclosed. Also disclosed are methods for treating an oncological, immunological, infectious or neurological disease or disorder, the method comprising administering to a subject in need of treatment thereof a therapeutically effective amount of a glutamine antagonist of the disclosure or the pharmaceutical composition thereof. Also disclosed are methods of enhancing the effects of an immune checkpoint inhibitor, enabling a subject to respond to an immune checkpoint inhibitor, or enabling the toxicity or the dose or number of treatments with an immune checkpoint inhibitor to be reduced, comprising administering to a subject in need of treatment thereof a therapeutically effective amount of a glutamine antagonist of the disclosure or the pharmaceutical composition thereof, and an immune checkpoint inhibitor. Also disclosed are methods for treating an oncological, immunological, infectious or neurological disease or disorder that is refractory to checkpoint inhibitor therapy, the method comprising administering to a subject in need thereof, and having the refractory disease or disorder, a therapeutically effective amount of a glutamine antagonist of the disclosure or the pharmaceutical composition thereof.

An object of the present invention is to provide novel crystals. Provided are crystals of 3-hydroxy-N′-(1,3-dimethylbutylidene)-2-naphthoic acid hydrazide having an X-ray powder diffraction pattern comprising a peak of maximum intensity at an angle of diffraction (2θ) of 6.1±0.2°.

Methods of detecting an aldehyde-containing compound in a subject or in a sample from a subject are described herein, comprising administering an aldehyde-binding compound of Formula I to the subject, or combining such a compound with the sample; and detecting the product of the compound of Formula I and the aldehyde-containing compound. Detection of the product may involve imaging, such as MRI, CEST-MRI or positron emission tomography (PET) imaging; or may involve fluorescence or an electrochemical detection method. Biologically relevant aldehydes detected according to the described method can be used to monitor conditions such as brain injury, neurodegenerative disorders such as Alzheimer's disease, diabetes, heart disease, and cancer. ##STR00001##

Methods of detecting an aldehyde-containing compound in a subject or in a sample from a subject are described herein, comprising administering an aldehyde-binding compound of Formula I to the subject, or combining such a compound with the sample; and detecting the product of the compound of Formula I and the aldehyde-containing compound. Detection of the product may involve imaging, such as MRI, CEST-MRI or positron emission tomography (PET) imaging; or may involve fluorescence or an electrochemical detection method. Biologically relevant aldehydes detected according to the described method can be used to monitor conditions such as brain injury, neurodegenerative disorders such as Alzheimer's disease, diabetes, heart disease, and cancer. ##STR00001##

An object of the present invention is to provide novel crystals. Provided are crystals of 3-hydroxy-N′-(1,3-dimethylbutylidene)-2-naphthoic acid hydrazide having an X-ray powder diffraction pattern comprising a peak of maximum intensity at an angle of diffraction (2θ) of 6.9°.

The invention relates to plasminogen activator-1 (PAI-1) inhibitor compounds and uses thereof in the treatment of any disease or disorder associated with elevated PAI-1. The invention includes, but is not limited to, the use of such compounds to prevent or reduce thrombosis and fibrosis, to promote thrombolysis, and to modulate lipid metabolism and treat diseases or disorders associated with elevated PAI-1, cholesterol, or lipid levels.

The invention relates to plasminogen activator-1 (PAI-1) inhibitor compounds and uses thereof in the treatment of any disease or disorder associated with elevated PAI-1. The invention includes, but is not limited to, the use of such compounds to prevent or reduce thrombosis and fibrosis, to promote thrombolysis, and to modulate lipid metabolism and treat diseases or disorders associated with elevated PAI-1, cholesterol, or lipid levels.

Disclosed herein are compounds that are selective DNA primase and/or gyrase inhibitors. Further disclosed are pharmaceutical compositions comprising these compounds, and the uses of these compounds for treating disorders associated with microbial infections.

Disclosed herein are compounds that are selective DNA primase and/or gyrase inhibitors. Further disclosed are pharmaceutical compositions comprising these compounds, and the uses of these compounds for treating disorders associated with microbial infections.

A method for treating a p62-mediated disease (e.g., multiple myeloma) in a subject, the method comprising administering to the subject a therapeutically effective amount of at least one p62-ZZ inhibitor compound.