An Advanced Mechanically Active Osteoarthritis-on-Chip Model to Test Injectable Therapeutic Formulations: The SYN321 Case Study.

Current treatments for osteoarthritis (OA) often fail to address the underlying pathophysiology and may have systemic side effects, particularly associated with long-term use of non-steroidal anti-inflammatory drugs (NSAIDs). Thus, researchers are currently directing their efforts toward innovative polymer-drug combinations, such as mixtures of hyaluronic acid viscoelastic hydrogels and NSAIDs like diclofenac, to ensure sustained release of the NSAID within the joint following intra-articular injection. However, the progress of novel injectable therapies for OA is hindered by the absence of preclinical models that accurately represent the pathology of the disease.

The Oncolytic Efficacy and in Vivo Pharmacokinetics of [2-(4-Chlorophenyl)quinolin-4-yl](piperidine-2-yl)methanol (Vacquinol-1) Are Governed by Distinct Stereochemical Features.

Glioblastoma remains an incurable brain cancer. Drugs developed in the past 20 years have not improved the prognosis for patients, necessitating the development of new treatments. We have previously reported the therapeutic potential of the quinoline methanol Vacquinol-1 (1) that targets glioblastoma cells and induces cell death by catastrophic vacuolization.

Substituted benzylamino-6-(trifluoromethyl)pyrimidin-4(1H)-ones: a novel class of selective human A-FABP inhibitors.

The synthesis and biological evaluation of novel human A-FABP inhibitors based on the 6-(trifluoromethyl)pyrimidine-4(1H)-one scaffold is described. Two series of compounds, bearing either an amino or carbon substituent in the 2-position of the pyrimidine ring were investigated. Modification of substituents and chain length optimization led to novel compounds with low micromolar activity and good selectivity for human A-FABP.

Design and synthesis of potent, orally active, inhibitors of carboxypeptidase U (TAFIa).

A series of 3-mercapto-propionic acid derivatives that function as reversible inhibitors of carboxypeptidase U have been prepared. We present a successful design strategy using cyclic, low basicity guanidine mimetics resulting in potent, selective and bioavailable inhibitors of carboxypeptidase U (TAFIa).