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Desarrollos recientes en PROTACs dirigidos a quinasas dependientes de ciclina (CDK) en terapia contra el cáncer

Arijit Nandi¹, Anwesha Das², M Rhia L Stone¹

¹Centre for Superbug Solutions, Institute for Molecular Bioscience, The University of Queensland, Brisbane 4067, Queensland Australia.

ACS medicinal chemistry letters

|December 17, 2025

Resumen

Los PROTAC (quimeras dirigidas a proteólisis) basados en quinasas dependientes de ciclina (CDK) son prometedores para el tratamiento del cáncer. Esta revisión cubre los avances de 2024 en PROTAC dirigidos a CDK, incluido el cribado computacional, las estrategias de enlazadores y las aplicaciones de ligasas E3.

Área de la Ciencia:

Oncología
Química Medicinal
Descubrimiento de Fármacos

Sus antecedentes:

Las quimeras dirigidas a proteólisis (PROTACs) representan una modalidad terapéutica novedosa.
Las quinasas dependientes de ciclina (CDKs) son reguladores cruciales del ciclo celular y a menudo se desregulan en el cáncer.
La orientación de las CDK con moléculas pequeñas ha sido una estrategia de larga data en oncología.

Objetivo del estudio:

Proporcionar una visión general completa del panorama actual del desarrollo de PROTAC contra el cáncer dirigido a la familia de las CDK.
Destacar los avances recientes y las estrategias emergentes en el diseño y la aplicación de PROTAC basados en CDK a partir de 2024.

Principales métodos:

Revisión de la literatura científica reciente y las solicitudes de patente relacionadas con PROTACs dirigidos a CDK.
Análisis de enfoques de cribado computacional para el diseño de PROTAC.
Discusión de las relaciones estructura-actividad (SAR) y las estrategias de optimización de enlazadores.
Exploración de estrategias de degradación alternativas y utilización de ligasas E3 novedosas.

Principales resultados:

Se han logrado avances significativos en el desarrollo de PROTACs dirigidos a CDK para diversos tipos de cáncer.
El cribado computacional ayuda a identificar posibles candidatos a PROTAC.
Se están explorando diversas químicas de enlazadores y ligasas E3 para optimizar la eficiencia y selectividad de la degradación.
Se están investigando estrategias para mejorar las propiedades farmacocinéticas de las moléculas heterobifuncionales.

Conclusiones:

Los PROTAC basados en CDK son un campo en rápida evolución con un potencial terapéutico sustancial en oncología.
La innovación continua en tecnología de enlazadores, reclutamiento de ligasas E3 y diseño molecular es clave para realizar su beneficio clínico completo.
Se necesita más investigación para optimizar las propiedades similares a las de los fármacos y la eficacia clínica en beneficio de los pacientes.

Palabras clave:

quimera heterobifuncional serina-treonina quinasa degradación de proteínas dirigida complejo ternario

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