A carregar...
Publicação
Inibidores de cinases em uso clínico
| Nome: | Descrição: | Tamanho: | Formato: | |
|---|---|---|---|---|
| 2.44 MB | Adobe PDF |
Autores
Orientador(es)
Resumo(s)
As cinases são enzimas que catalisam a transferência do grupo γ-fosfato do ATP para um substrato proteico. Os inibidores de cinases são uma classe de fármacos que têm como alvo específico o bloqueio da atividade das cinases, através da ligação ao sítio ativo da cinase alvo, o que impede a interação desta com o ATP. Estes inibidores, que têm vindo a revolucionar a terapêutica de diversas patologias ao longo das últimas duas décadas, podem ser classificados de acordo com o seu modo de ligação (reversível ou irreversível) e, dentro dos inibidores reversíveis, estes podem ser classificados em quatro tipos principais (I-IV) com base no seu sítio de ligação, conformação da cinase e tipo de competição com o ATP.
Por esta ser uma área em constante evolução, o objetivo deste trabalho é fazer uma revisão dos principais inibidores de cinases que se encontram em uso clínico. É referida a sua indicação clínica e feita uma comparação a nível estrutural, modo de ligação e ação, bem como analisados os efeitos adversos e resistências a estes, que levam ao desenvolvimento de novos inibidores de cinases. É também feita uma breve menção a inibidores que se encontram em ensaios pré-clínicos e clínicos. Este objetivo é alcançado através da análise de diversos artigos científicos recentes e bibliografia relevante para o tema, de forma a obter-se a informação mais atualizada possível.
Após recolha da informação e análise da mesma, é possível compreender que, devido às mutações que vão surgindo ao longo do tempo, novas gerações de inibidores de cinases têm surgido. As principais limitações no desenvolvimento destes inibidores é a eficácia e toxicidade dos mesmos, no entanto, o uso de terapêuticas combinadas é uma solução que tem conseguido ultrapassar este problema.
Confirmadas as mais-valias que estes inibidores têm trazido na prática clínica, é de extrema importância uma análise sobre os inibidores já desenvolvidos para que, no futuro, seja possível o desenvolvimento de novos inibidores que consigam ultrapassar as mutações já existentes e que haverão de surgir, bem como o desenvolvimento de novos inibidores para outras áreas terapêuticas.
Kinases are enzymes that catalyze the transfer of the v-phosphate group from ATP to a protein substrate. Kinase inhibitors are a class of drugs that specifically target and block kinase activity by binding to the active site of the target kinase, thereby preventing its interaction with ATP. These inhibitors, which have revolutionized the treatment of various diseases over the past two decades, can be classified according to their mode of binding (reversible or irreversible). Among reversible inhibitors, they can be further classified into four main types (I-IV) based on their binding site, kinase conformation, and type of competition with ATP. As this is an ever-evolving field, the objective of this work is to review the main kinase inhibitors currently in clinical use. Their clinical indications are mentioned, and a comparison is made in terms of structure, mode of binding and action, as well as analyzing the adverse effects and resistances that lead to the development of new kinase inhibitors. A brief mention is also made of inhibitors currently in preclinical and clinical trials. This objective is achieved through the analysis of various recent scientific articles and relevant bibliography on the subject to obtain the most up-to-date information possible. After gathering and analyzing the information, it is possible to understand that due to mutations that emerge over time, new generations of kinase inhibitors have been developed. The main limitations in the development of these inhibitors are their efficacy and toxicity; however, the use of combination therapies is a solution that has managed to overcome this problem. Given the confirmed benefits that these inhibitors have brought to clinical practice, it is extremely important to analyze the inhibitors already developed so that, in the future, it will be possible to develop new inhibitors that can overcome existing and emerging mutations, as well as the development of new inhibitors for other therapeutic areas.
Kinases are enzymes that catalyze the transfer of the v-phosphate group from ATP to a protein substrate. Kinase inhibitors are a class of drugs that specifically target and block kinase activity by binding to the active site of the target kinase, thereby preventing its interaction with ATP. These inhibitors, which have revolutionized the treatment of various diseases over the past two decades, can be classified according to their mode of binding (reversible or irreversible). Among reversible inhibitors, they can be further classified into four main types (I-IV) based on their binding site, kinase conformation, and type of competition with ATP. As this is an ever-evolving field, the objective of this work is to review the main kinase inhibitors currently in clinical use. Their clinical indications are mentioned, and a comparison is made in terms of structure, mode of binding and action, as well as analyzing the adverse effects and resistances that lead to the development of new kinase inhibitors. A brief mention is also made of inhibitors currently in preclinical and clinical trials. This objective is achieved through the analysis of various recent scientific articles and relevant bibliography on the subject to obtain the most up-to-date information possible. After gathering and analyzing the information, it is possible to understand that due to mutations that emerge over time, new generations of kinase inhibitors have been developed. The main limitations in the development of these inhibitors are their efficacy and toxicity; however, the use of combination therapies is a solution that has managed to overcome this problem. Given the confirmed benefits that these inhibitors have brought to clinical practice, it is extremely important to analyze the inhibitors already developed so that, in the future, it will be possible to develop new inhibitors that can overcome existing and emerging mutations, as well as the development of new inhibitors for other therapeutic areas.
Descrição
Trabalho Final de Mestrado Integrado, Ciências Farmacêuticas, 2024, Universidade de Lisboa, Faculdade de Farmácia.
Palavras-chave
Cinases Inibidores de cinases Cancro Modo de ligação Mutações Mestrado integrado - 2024