RESUMO
Abnormality of the B-cell receptor (BCR) signaling is correlated to origin of many B-cell malignancies. Bruton's tyrosine kinase (BTK), is described as a possible target in a many B-cell neoplasms. Ibrutinib is the most used inhibitor of BTK and has great tolerability and efficacy in chronic lymphocytic leukemia. This review summarizes results with ibrutinib in clinical trials and novel BTK inhibitors of interest.
Assuntos
Antineoplásicos/farmacologia , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Inibidores de Proteínas Quinases/farmacologia , Proteínas Tirosina Quinases/antagonistas & inibidores , Pirazóis/farmacologia , Pirimidinas/farmacologia , Adenina/análogos & derivados , Tirosina Quinase da Agamaglobulinemia , Antineoplásicos/química , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Leucemia Linfocítica Crônica de Células B/metabolismo , Estrutura Molecular , Piperidinas , Inibidores de Proteínas Quinases/química , Proteínas Tirosina Quinases/metabolismo , Pirazóis/química , Pirimidinas/química , Relação Estrutura-AtividadeRESUMO
Bortezomib was the first proteasome inhibitor (PI) discovered and demonstrated great efficacy in myeloma, both in vitro and in patients. However, still many patients ultimately relapse and there is the need for novel therapies. A second generation of PI have been discovered, potentially more effective ands some also orally administered. Carfilzomib is an irreversible proteasome inhibitor that showed great efficacy in clinical studies. Ixazomib is an oral compound that has been introduced recently in the therapeutic spectrum. Novel agents such as Marizomib seem promising in the fact that can also pass through the blood brain barrier and maybe effective also in CNS muyeloma. This review focus on all proteasome inhibitors available in clinics and the new ones coming soon.
