5 research outputs found
Comparison of serum levels of Th1 and Th17 related cytokines between PSS patients and controls.
<p>Comparison of serum levels of Th1 and Th17 related cytokines between PSS patients and controls.</p
Comparison of serum positive rate of CMV-IgG and CMV-IgM between PSS patients and controls.
<p>Comparison of serum positive rate of CMV-IgG and CMV-IgM between PSS patients and controls.</p
Comparison of serum positive rates of autoantibodies between PSS patients and controls.
<p>Comparison of serum positive rates of autoantibodies between PSS patients and controls.</p
Demographic and clinical features of PSS patients and controls.
<p>Demographic and clinical features of PSS patients and controls.</p
Life Beyond Kinases: Structure-Based Discovery of Sorafenib as Nanomolar Antagonist of 5-HT Receptors
Of great interest in recent years has been computationally
predicting
the novel polypharmacology of drug molecules. Here, we applied an
“induced-fit” protocol to improve the homology models
of 5-HT<sub>2A</sub> receptor, and we assessed the quality of these
models in retrospective virtual screening. Subsequently, we computationally
screened the FDA approved drug molecules against the best induced-fit
5-HT<sub>2A</sub> models and chose six top scoring hits for experimental
assays. Surprisingly, one well-known kinase inhibitor, sorafenib,
has shown unexpected promiscuous 5-HTRs binding affinities, <i>K</i><sub>i</sub> = 1959, 56, and 417 nM against 5-HT<sub>2A</sub>, 5-HT<sub>2B</sub>, and 5-HT<sub>2C</sub>, respectively. Our preliminary
SAR exploration supports the predicted binding mode and further suggests
sorafenib to be a novel lead compound for 5HTR ligand discovery. Although
it has been well-known that sorafenib produces anticancer effects
through targeting multiple kinases, carefully designed experimental
studies are desirable to fully understand whether its “off-target”
5-HTR binding activities contribute to its therapeutic efficacy or
otherwise undesirable side effects