Now showing items 1-10 of 58
A Potential New Treatment Paradigm for Multiple Sclerosis
This project was completed with contributions from Alexei Degterev from the Department of Developmental, Molecular and Chemical Biology, School of Medicine, Tufts University, Boston.
The Structural Basis of Cryptosporidium-Specific IMP Dehydrogenase Inhibitor Selectivity
(Journal of the American Chemical Society, 2/3/2011)
Cryptosporidium parvum is a potential biowarfare agent, an important AIDS pathogen, and a major cause of diarrhea and malnutrition. No vaccines or effective drug treatment exist to combat Cryptosporidium infection. This ...
Selective and potent urea inhibitors of Cryptosporidium parvum inosine 5’-monophosphate dehydrogenase
(Journal of Medicinal Chemistry, 2013-09)
Cryptosporidium parvum and related species are zoonotic intracellular parasites of the intestine. Cryptosporidium is a leading cause of diarrhea in small children around the world. Infection can cause severe pathology in ...
Optimization of a series of heterocycles as survival motor neuron gene transcription enhancers
(Bioorganic and Medicinal Chemistry Letters, 12/1/2018)
Spinal muscular atrophy (SMA) is a neurodegenerative disorder that results from mutations in the SMN1 gene, leading to survival motor neuron (SMN) protein deficiency. One therapeutic strategy for SMA is to identify compounds ...
Structure–activity relationship study of acridine analogs as haspin and DYRK2 kinase inhibitors
(Bioorganic and Medicinal Chemistry Letters, 6/15/2011)
Haspin is a serine/threonine kinase required for completion of normal mitosis that is highly expressed during cell proliferation, including in a number of neoplasms. Consequently, it has emerged as a potential therapeutic ...
Restored glial glutamate transporter EAAT2 function as a potential therapeutic approach for Alzheimer’s disease
(Journal of Experimental Medicine, 2015-02)
Glutamatergic systems play a critical role in cognitive functions and are known to be defective in Alzheimer’s disease (AD) patients. Previous literature has indicated that glial glutamate transporter EAAT2 plays an essential ...
Fluorescence polarization assay for inhibitors of the kinase domain of receptor interacting protein 1
(Analytical Biochemistry, 2013-05)
Necrotic cell death is prevalent in many different pathological disease states and in traumatic injury. Necroptosis is a form of necrosis that stems from specific signaling pathways, with the key regulator being receptor ...
Structure–activity relationship and liver microsome stability studies of pyrrole necroptosis inhibitors
(Bioorganic and Medicinal Chemistry Letters, 2009-06)
Necroptosis is a regulated caspase-independent cell death pathway resulting in morphology reminiscent of passive non-regulated necrosis. Several diverse structure classes of necroptosis inhibitors have been reported to ...
Enzymatic Characterization of ER Stress-Dependent Kinase, PERK, and Development of a High-Throughput Assay for Identification of PERK Inhibitors
(Journal of Biomolecular Screening, 2015-09)
PERK is serine/threonine kinase localized to the endoplasmic reticulum (ER) membrane. PERK is activated and contributes to cell survival in response to a variety of physiological stresses that affect protein quality control ...
Type II Kinase Inhibitors Show an Unexpected Inhibition Mode against Parkinson’s Disease-Linked LRRK2 Mutant G2019S
A number of well-known type II inhibitors (ATP-noncompetitive) that bind kinases in their DFG-out conformation were tested against wild-type LRRK2 and the most common Parkinson’s disease-linked mutation, G2019S. We found ...