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.
Glutamate transporter EAAT2: a new target for the treatment of neurodegenerative diseases
(Future Medicinal Chemistry, 2013-07)
Glutamate is the primary excitatory amino acid neurotransmitter in the CNS. The concentration of glutamate in the synaptic cleft is tightly controlled by interplay between glutamate release and glutamate clearance. Abnormal ...
Characterization of the 8-hydroxyquinoline scaffold for inhibitors of West Nile virus serine protease
(Antiviral Research, 2013-04)
West Nile virus (WNV) is a mosquito-borne member of flaviviruses that causes significant morbidity and mortality especially among children. There is currently no approved vaccine or antiviral therapeutic for human use. In ...
Structure–activity relationship study of 2,4-diaminothiazoles as Cdk5/p25 kinase inhibitors
(Bioorganic and Medicinal Chemistry Letters, 2012-04)
Cdk5/p25 has emerged as a principle therapeutic target for numerous acute and chronic neurodegenerative diseases, including Alzheimer’s disease. A structure–activity relationship study of 2,4-diaminothiazole inhibitors ...
Small-Molecule Inhibitors of USP1 Target ID1 Degradation in Leukemic Cells
(Molecular Cancer Therapeutics, 2014-12)
Inhibitor of DNA binding 1 (ID1) transcription factor is essential for the proliferation and progression of many cancer types, including leukemia. However, the ID1 protein has not yet been therapeutically targeted in ...
Diaminothiazoles Modify Tau Phosphorylation and Improve the Tauopathy in Mouse Models
(Journal of BIological Chemistry, 2013-07)
Although Tau accumulation is a feature of several neurodegenerative conditions, treatment options for these conditions are nonexistent. Targeting Tau kinases represents a potential therapeutic approach. Small molecules in ...
Structure of Cryptosporidium IMP dehydrogenase bound to an inhibitor with in vivo antiparasitic activity
(Acta Crystallographica, 2015-01)
Inosine 50-monophosphate dehydrogenase (IMPDH) is a promising target for the treatment of Cryptosporidium infections. Here, the structure of C. parvum IMPDH (CpIMPDH) in complex with inosine 50-monophosphate (IMP) and P131, ...
In Vivo and In Vitro Pharmacological Studies of Methoxycarbonyl-Carboetomidate
(Anethesia and Analgesia, 2013-08)
Background—We previously developed two etomidate analogs that retain etomidate’s favorable hemodynamic properties, but whose adrenocortical effects are reduced in duration or magnitude. Methoxycarbonyl-etomidate (MOC-etomidate) ...
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 ...
Optimization of tricyclic Nec-3 necroptosis inhibitors for in vitro liver microsomal stability
(Bioorganic and Medicinal Chemistry Letters, 2013-09)
Necroptosis is a regulated caspase-independent cell death pathway with morphological features resembling passive non-regulated necrosis. Several diverse structure classes of necroptosis inhibitors have been reported to ...