3 research outputs found
Discovery of FDA-Approved Drugs as Inhibitors of Fatty Acid Binding Protein 4 Using Molecular Docking Screening
We first identified fluorescein,
ketazolam, antrafenine, darifenacin,
fosaprepitant, paliperidone, risperidone, pimozide, trovafloxacin,
and levofloxacin as inhibitors of fatty acid binding protein 4 using
molecular docking screening from FDA-approved drugs. Subsequently,
the biochemical characterizations showed that levofloxacin directly
inhibited FABP4 activity in both the <i>in vitro</i> ligand
displacement assay and cell-based function assay. Furthermore, levofloxacin
did not induce adipogenesis in adipocytes, which is the major adverse
effect of FABP4 inhibitors
Discovery of a Novel HIVā1 Integrase/p75 Interacting Inhibitor by Docking Screening, Biochemical Assay, and in Vitro Studies
Proteināprotein
interaction between lens epithelium-derived growth factor (LEDGF/p75)
and HIV-1 integrase becomes an attractive target for anti-HIV drug
development. The blockade of this interaction by small molecules could
potentially inhibit HIV-1 replication. These small molecules are termed
as LEDGINs; and several newly identified LEDGINs have been reported
to significantly reduce HIV-1 replication. Through this project, we
have finished the docking screening of the Maybridge database against
the p75 binding site of HIV-1 integrase using both DOCK and Autodock
Vina software. Finally, we have successfully identified a novel scaffold
LEDGINs inhibitor DW-D-5. Its antiviral activities and anticatalytic
activity of HIV-1 integrase are similar to other LEDGINs under development.
We demonstrated that the combination of DW-D-5 and FDA approved anti-HIV
drugs resulted in additive inhibitory effects on HIV-1 replication,
indicating that DW-D-5 could be an important component of combination
pills for clinic use in HIV treatment
Pimozide, a Novel Fatty Acid Binding Protein 4 Inhibitor, Promotes Adipogenesis of 3T3-L1 Cells by Activating PPARĪ³
Pimozide is a conventional antipsychotic
of the diphenylbutylpiperidine
class that has been clinically used for over 30 years. The obvious
side effect of this drug is weight gain. However, the mechanism of
pimozide-induced weight gain is still unknown. In the present study,
we identified pimozide as a novel fatty acid binding protein 4 (FABP4)
inhibitor using molecular docking simulation as well as biochemical
characterizations. BMS309403, a well-known FABP4 inhibitor, elevated
the basal protein levels of PPARĪ³, therefore stimulating adipogenesis
in adipocytes. The present study showed that the inhibitory effect
of pimozide on FABP4 promoted adipocyte differentiation with the potency
proportional to their propensities for weight gain. These effects
in adipogenesis by pimozide may help to explain the weight gain that
is frequently observed in patients treated with pimozide