Region-independent active CNS net uptake of marketed H/OC antiporter system substrates.

The pyrilamine-sensitive proton-coupled organic cation (H/OC) antiporter system facilitates the active net uptake of several marketed organic cationic drugs across the blood-brain barrier (BBB). This rare phenomenon has garnered interest in the H/OC antiporter system as a potential target for CNS drug delivery. However, analysis of pharmacovigilance data has uncovered a significant association between substrates of the H/OC antiporter and neurotoxicity, particularly drug-induced seizures (DIS) and mood- and cognitive-related adverse events (MCAEs).

Multiantigen T-Cell Hybridizers: A Two-Component T-Cell-Activating Therapy.

Multispecific T-cell-engaging scaffolds have emerged as effective anticancer therapies for the treatment of hematological malignancies. Approaches that modulate cancer cell targeting and provide personalized, multispecific immunotherapeutics are needed. Here, we report on a modular, split antibody-like approach consisting of Fab' fragments modified with complementary morpholino oligonucleotides (MORFs).

Synthesis and anticancer activity of new coumarin-3-carboxylic acid derivatives as potential lactatetransportinhibitors.

As an oncometabolite, lactate plays a very important role in tumor proliferation, metastasis, angiogenesis, immune escape and other tumor biological functions. Pharmacological inhibition oflactate transport has been viewed as a promising therapeutic strategy to target a range of human cancers. In this study, a series of new coumarin-3-carboxylic acid derivatives 5a-t and 9a-b were synthesized and evaluated as lactate transport inhibitors.