A5081701250- Cholinesterase and Neurodegenerative Diseases
- Amyotrophic Lateral Sclerosis Research
- Histone Deacetylase Inhibitors Research
- Graphene and Nanomaterials Applications
- Phosphodiesterase function and regulation
- Advanced Drug Delivery Systems
- Cancer Treatment and Pharmacology
- Dendrimers and Hyperbranched Polymers
- Protein Kinase Regulation and GTPase Signaling
- Immunodeficiency and Autoimmune Disorders
- Cancer therapeutics and mechanisms
- biodegradable polymer synthesis and properties
- Nerve injury and regeneration
- Parkinson's Disease and Spinal Disorders
- Computational Drug Discovery Methods
- Pharmaceutical studies and practices
- Supramolecular Self-Assembly in Materials
- 14-3-3 protein interactions
- Bipolar Disorder and Treatment
Centro de Investigaciones Biológicas Margarita Salas
2020-2024
Phosphodiesterase 7 (PDE7) is an enzyme responsible for the degradation of cyclic adenosine monophosphate (cAMP), important cellular messenger. PDE7’s role in neurotransmission, expression profile brain and druggability other phosphodiesterases have motivated search potent inhibitors to treat neurodegenerative inflammatory diseases. Different heterocyclic compounds been described over years; among them, phenyl-2-thioxo-(1H)-quinazolin-4-one, called S14, has shown very promising results...
TDP-43 has been identified as the major component of protein aggregates found in affected neurons FTLD-TDP and amyotrophic lateral sclerosis (ALS) patients. is hyperphosphorylated, ubiquitinated, cleaved C-terminus. CDC-7 was reported to phosphorylate TDP-43. There are no effective treatments for either or ALS, being a pressing need search new therapies. We hypothesized that modulating activity with small molecules able interfere phosphorylation could be good therapeutic strategy these...
A potent cell division cycle 7 (CDC7) kinase inhibitor, known as PHA-767491, has been described to reduce the transactive response DNA binding protein of 43 KDa (TDP-43) phosphorylation in vitro and vivo, which is one main proteins found aggregate accumulate cytoplasm motoneurons amyotrophic lateral sclerosis (ALS) frontotemporal dementia (FTD) patients. However, drawback this compound its low permeability central nervous system (CNS), limiting use for treatment neurological conditions. In...
Cell division cycle 7 kinase (CDC7) has been found overexpressed in many cancer cell lines being also one of the kinases involved nuclear protein TDP-43 phosphorylation vivo. Thus, inhibitors CDC7 are emerging drug candidates for treatment oncological and neurodegenerative unmet diseases. All known ATP-competitives, lacking selectivity enough success clinical trials. As allosteric sites less conserved among proteins, discovery modulators is a great challenge opportunity this field.