Noticias
Publicado el artículo "Targeting transthyretin in Alzheimer's disease: Drug discovery of small-molecule chaperones as disease-modifying drug candidates for Alzheimer's disease"
El Dr. Rafel Prohens, responsable de la Unidad de Polimorfismo y Calorimetría dels CCiTUB, conjuntamente con investigadores/as de otras instituciones, ha publicado el artículo
"Targeting transthyretin in Alzheimer's disease: Drug discovery of small-molecule chaperones as disease-modifying drug candidates for Alzheimer's disease" en la revista European Journal of Medicinal Chemistry.
El artículo contiene como conclusiones más destacadas:
• La transtiretina tiene un papel bien establecido en la neuroprotección de la enfermedad de Alzheimer
• El Iododiflunisal es un acompañante de la interacción transtiretina / Aβ
• Se han descubierto compuestos con la misma actividad de acompañamiento que el Iododiflunisal
• Entre los acompañantes, se descubrieron tres medicamentos registrados que se pueden reutilizar
• Se utilizaran para validar la transtiretina como nuevo objetivo de la enfermedad de Alzheimer
El resumen del artículo es el siguiente:
"Transthyretin (TTR) has a well-established role in neuroprotection in Alzheimer's Disease (AD). We have setup a drug discovery program of small-molecule compounds that act as chaperones enhancing TTR/Amyloid-beta peptide (Aβ) interactions. A combination of computational drug repurposing approaches and in vitro biological assays have resulted in a set of molecules which were then screened with our in-house validated high-throughput screening ternary test. A prioritized list of chaperones was obtained and corroborated with ITC studies. Small-molecule chaperones have been discovered, among them our lead compound Iododiflunisal (IDIF), a molecule in the discovery phase; one investigational drug (luteolin); and 3 marketed drugs (sulindac, olsalazine and flufenamic), which could be directly repurposed or repositioned for clinical use. Not all TTR tetramer stabilizers behave as chaperones in vitro. These chemically diverse chaperones will be used for validating TTR as a target in vivo, and to select one repurposed drug as a candidate to enter clinical trials as AD disease-modifying drug."