Structural Analysis of Janus Tyrosine Kinase Variants in Hematological Malignancies: Implications for Drug Development and Opportunities for Novel Therapeutic Strategies.

Janus tyrosine kinase (JAK) variants are known drivers for hematological disorders. With the full-length structure of mouse JAK1 being recently resolved, new observations on the localization of variants within closed, open, and dimerized JAK structures are possible. Full-length homology models of human wild-type JAK family members were developed using the Glassman et al.

Nanocarriers as Potential Drug Delivery Candidates for Overcoming the Blood-Brain Barrier: Challenges and Possibilities.

The design of a drug that successfully overcomes the constraints imposed by the blood-brain barrier (BBB, which acts as a gatekeeper to the entry of substances into the brain) requires an understanding of the biological firewall. It is also of utmost importance to understand the physicochemical properties of the said drug and how it engages the BBB to avoid undesired side effects. Since fewer than 5% of the tested molecules can pass through the BBB, drug development pertaining to brain-related disorders takes inordinately long to develop.

Relationship of light scatter change and Cdc42-regulated actin status.

Background: Cdc42 GTPase has important roles in regulating intracellular actin reorganization. The current methods to monitor actin changes are typically complex and point by point.

Methods: The effects of Cdc42 inhibitors on the side scatter changes were tested in a newly developed continuous assay using the flow cytometer.

A selective ATP-binding cassette subfamily G member 2 efflux inhibitor revealed via high-throughput flow cytometry.

Chemotherapeutics tumor resistance is a principal reason for treatment failure, and clinical and experimental data indicate that multidrug transporters such as ATP-binding cassette (ABC) B1 and ABCG2 play a leading role by preventing cytotoxic intracellular drug concentrations. Functional efflux inhibition of existing chemotherapeutics by these pumps continues to present a promising approach for treatment. A contributing factor to the failure of existing inhibitors in clinical applications is limited understanding of specific substrate/inhibitor/pump interactions.

A novel flow cytometric HTS assay reveals functional modulators of ATP binding cassette transporter ABCB6.

ABCB6 is a member of the adenosine triphosphate (ATP)-binding cassette family of transporter proteins that is increasingly recognized as a relevant physiological and therapeutic target. Evaluation of modulators of ABCB6 activity would pave the way toward a more complete understanding of the significance of this transport process in tumor cell growth, proliferation and therapy-related drug resistance. In addition, this effort would improve our understanding of the function of ABCB6 in normal physiology with respect to heme biosynthesis, and cellular adaptation to metabolic demand and stress responses.