and animal welfare are important factors in the development of new drugs.
Considering this, Nakamura et al.
propose a new way of predicting human PK for mAbs that is more efficient than
conventional methods. By collecting mAb PK data on linear elimination and
analyzing a two-compartment model, they revealed that half-life during
elimination is the main contributor to plasma clearance. Based on this feature,
they developed a novel method that uses easy-to-obtain parameters from humans
and non-human primates to predict human PK. Called the half-life method, it can
improve animal welfare and potentially accelerate the drug development process.
(ETZ) is widely used as an OTC pain reliever, however, its site of action and
mechanism underlying its analgesic action had not yet been fully elucidated.
The article by Nikaido et al. provides evidence suggesting that the
analgesic effect of ETZ in the rat formalin test was mediated by multiple
mechanisms of action including the 5-hydroxytryptamine2B receptor
blockade at the spinal cord.
angiogenesis is a leading cause of blindness in several retinal diseases. Kondo
et al. demonstrated that only a 2-day treatment of neonatal rats with the VEGF
receptor tyrosine kinase inhibitor at different time points could induce
abnormal blood vessels with different vascular pathological features (intravitreal
neovascularization vs. tortuous arteries) in the retina. Pharmacological agents
targeting the VEGF signaling pathway are useful for creating an abnormal
retinal vasculature with various pathological features in order to study the
mechanisms underlying abnormal retinal angiogenesis and evaluate the efficacy
of anti-angiogenic compounds.
fentanyl patch (FP) has been used worldwide to relieve cancer pain. However, no
previous studies have examined the influence of cancer cachexia on pain control
in cancer patients receiving FP treatment. Chiba et al. found that cancer
cachexia may be a risk factor for poor pain control in patients receiving FP
treatment, and that uncontrolled pain in FP treatment may be caused by the
inhibition of fentanyl transdermal absorption due to dry skin.
To discover small molecules that affect
osteoclastogenesis, Kumagai et al designed and synthesized styrylpyrone
analogs, and discovered (E)-6-(2-fluorostyryl)-4-methoxy-2H-pyran-2-one (22) has osteoclast-inhibitory activities in murine RAW264 cells. A
partial structure-activity relationship revealed that fluorine and its position
within the styrylpyrone skeleton were important. Authors also revealed that compound
22 prevents osteoclastic bone
resorption by inhibiting osteoclastogenesis. Compound 22 downregulated mRNA expression levels of RANKL-induced nuclear
factor of activated T cells c1 (NFATc1) and osteoclastogenesis-related genes.
These findings may be useful for the desigh of antiresorptive agents for the
treatment of bone disorders characterized by excessive osteoclastic activity .