The present specification discloses a retargeted endopeptidase pharmaceutical wherein the activity has been determined by the methods disclosed.

The present invention relates to pharmaceutical combinations and compositions, and methods of using the same for treatment of attention deficit hyperactivity disorder (ADHD) and bipolar disorder (BD). The invention relates to combination therapies for the treatment of BD and for ADHD, and methods for treating BD and ADHD using such therapies. The present invention also relates to methods of determining an optimal combination drug treatment therapy for BD and for ADHD, methods of optimizing a combination drug treatment therapy for BD and for ADHD, methods of optimizing dosage of a drug in a combination drug treatment therapy for BD and for ADHD, as well as methods for monitoring the efficacy of a combination therapy for the treatment of BD and for ADHD. The present invention involves analyzing the membrane potential of cells isolated from a BD patient treated with the combination therapy and from an ADHD patient treated with the combination therapy, and calculating a membrane potential ratio therefrom.

The present invention provides a method for measuring a cellular uptake amount of a molecule, comprising (i) adding the molecule to an organ-derived cell population to perform incubation, (ii) sorting the organ-derived cell population based on the expression levels of CD31 and CD45, and (iii) after steps (i) and (ii), measuring the amount of the molecule incorporated into the cell population sorted in the step (ii), wherein the molecule is incorporated into cells via a cell surface receptor.

Disclosed is a method for analyzing immune cells, comprising the steps of mixing whole blood containing immune cells with an immunostimulatory factor in vitro and labeling target molecules of the immune cells, and a step of acquiring information on localization of the target molecules on the immune cells by detecting the label.

The present invention is directed to compositions and methods for modulating c-Rel-dependent cytokine production without materially altering the level of expression of NFκB and/or the amount of IκB. The present invention is also directed to screening for modulators of c-Rel activity as determined by assaying for altered subcellular localization of c-Rel but where the level of expression of NFκB and/or the amount of IκB is materially unaltered.

Compounds of the present invention and pharmaceutically acceptable compositions thereof, are useful as modulators of ATP-Binding Cassette (“ABC”) transporters or fragments thereof, including Cystic Fibrosis Transmembrane Conductance Regulator (“CFTR”). The present invention also relates to methods of treating ABC transporter mediated diseases using compounds of the present invention.

Methods and reagents for determining treatment efficacy of a MALT1 inhibitor in a human subject are described. The method involves determining NF-κB nuclear translocation in stimulated PBMCs of a blood sample obtained from the subject. The method provides information for guiding treatment decisions for those subjects receiving a MALT1 inhibitor therapy, improves the accuracy of optimizing therapy, reduces toxicity, and/or monitors the efficacy of therapeutic treatment.

Compositions including small molecule mitofusin activators are described. The mitofusin activators are useful for treating diseases or disorders associated with a mitochondria-associated disease, disorder, or condition such as diseases or disorders associated with mitofusin 1 (MFN1) and/or mitofusin 2 (MFN2), or mitochondrial dysfunction. Methods of treatment, pharmaceutical formulations, and screening methods for identifying compounds that activate mitochondrial fusion are also described.

The present disclosure relates to methods for screening test samples or substances that are capable of inducing or reducing nucleolar hypertrophy in cancer cells. The present disclosure further provides methods of contacting isolated cancer cells with a test sample or a substance that can induce nucleolar hypertrophy in a cancer cell. The present disclosure further provides methods for contacting an isolated cancer cell characterized by nucleolar hypertrophy with a test sample or substance that can reduce the nucleolar hypertrophy. One benefit to the method of screening disclosed herein can be the identification of test samples or substances capable of reducing nucleolar hypertrophy. Another benefit to the method of screening disclosed herein can be the identification of those combinations of test samples, substances, or combinations or series thereof, which are suitable or optimal for treating specific cancers in patients.

Compositions including small molecule mitofusin activators are described. The mitofusin activators are useful for treating diseases or disorders associated with a mitochondria-associated disease, disorder, or condition such as diseases or disorders associated with mitofusin 1 (MFN1) and/or mitofusin 2 (MFN2), or mitochondrial dysfunction. Methods of treatment, pharmaceutical formulations, and screening methods for identifying compounds that activate mitochondrial fusion are also described.