Matthew J. Shumway

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Fragile X syndrome (FXS), the most common inherited cause of intellectual disability and autism, results from the transcriptional silencing of FMR1 and loss of the mRNA translational repressor protein fragile X mental retardation protein (FMRP). Patients with FXS exhibit changes in neuronal dendritic spine morphology, a pathology associated with altered(More)
Nitric oxide (NO) enhances anti-inflammatory drug action. Through a metabonomics approach termed "NObonomics," the effects of a prototypic NO donor (organic nitrate)-cyclooxygenase-2 inhibitor hybrid (NO-coxib), NMI-1093, on the NO metabolite status of the circulation and major organs have been profiled in vivo in the rat. An oral anti-inflammatory NMI-1093(More)
The synthesis of a series of novel pyrazoles containing a nitrate (ONO(2)) moiety as a nitric oxide (NO)-donor functionality is reported. Their COX-1 and COX-2 inhibitory activities in human whole blood are profiled. Our data demonstrate that pyrazole ring substituents play an important role in COX-2 selective inhibition, such that a cycloalkyl pyrazole(More)
Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used to treat inflammation and to provide pain relief but suffer from a major liability concerning their propensity to cause gastric damage. As nitric oxide (NO) is known to be gastro-protective we have synthesized a NO-donating prodrug of naproxen named NMI-1182. We evaluated two cyclo-oxygenase(More)
Cyclooxygenase (COX, EC 1.14.99.1) inhibitor-nitric oxide (NO) donor (CINOD) hybrid compounds represent an attractive alternative to NSAID and coxib therapy. This report compares two CINODs, NMI-1182 (naproxen-glyceryl dinitrate) and AZD3582 (naproxen-n-butyl nitrate), for their ability to inhibit COX-1 and -2, deliver bioavailable nitric oxide, and release(More)
The combination of a nitric oxide (NO) donor and a paclitaxel-NO donor conjugate coated on a vascular stent was tested in a rabbit iliac artery model of stenosis as a potential therapy for restenosis. Paclitaxel was conjugated with a NO donor at the 7-position to give compound 7. An adamantane-based NO donor 14 was synthesized and combined with 7 to provide(More)
Incorporation of a spacer group between the central scaffold and the aryl ring resulted in a new cyclooxygenase-2 (COX-2) selective inhibitor core structure, 3-[4-(methylsulfonyl)phenyl]-5-(trifluoromethyl)(2-pyridyl) phenyl ketone (20), with COX-2 IC50 = 0.25 microM and COX-1 IC50 = 14 microM (human whole blood assay). Compound 20 was orally active in the(More)
A novel series of benzo-1,3-dioxolane metharyl derivatives was synthesized and evaluated for cyclooxygenase-2 (COX-2) and cyclooxygenase-1 (COX-1) inhibition in human whole blood (HWB). In the present study, structure-activity relationships (SAR) in the metharyl analogues were investigated. The spacer group and substitutions in the spacer group were found(More)
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