Synthetic lethality: targeting SMARCA2 ATPase in SMARCA4-deficient tumors - a review of patent literature from 2019-30 June 2023.
Expert Opin Ther Pat
; 34(3): 159-169, 2024 Mar.
Article
em En
| MEDLINE
| ID: mdl-38578210
ABSTRACT
INTRODUCTION:
The multi-subunit SWI/SNF chromatin remodeling complex is a key epigenetic regulator for many cellular processes, and several subunits are found to be mutated in human cancers. The inactivating mutations of SMARCA4, the ATPase subunit of the complex, result in cellular dependency on the paralog SMARCA2 for survival. This observed synthetic lethal relationship posits targeting SMARCA2 in SMARCA4-deficient settings as an attractive therapeutic target in oncology. AREAS COVERED This review covers patent literature disclosed during the 2019-30 June 2023 period which claim ATPase inhibitors and PROTAC degraders that bind to the ATPase domain of SMARCA2 and/or SMARCA4. A total of 16 documents from 6 applicants are presented. EXPERT OPINION The demonstration of cellular dependence on SMARCA2 ATPase activity in SMARCA4-deficient settings has prompted substantial research toward SMARCA2-targeting therapies. Although selectively targeting the ATPase domain of SMARCA2 is viewed as challenging, several ATPase inhibitor scaffolds have been disclosed within the last five years. Most early compounds are weakly selective, but these efforts have culminated in the first dual SMARCA2/SMARCA4 ATPase inhibitor to enter clinical trials. Data from the ongoing clinical trials, as well as continued advancement of SMARCA2-selective ATPase inhibitors, are anticipated to significantly impact the field of therapies, targeting SMARCA4-deficient tumors.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Patentes como Assunto
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Fatores de Transcrição
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Proteínas Nucleares
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DNA Helicases
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Terapia de Alvo Molecular
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Neoplasias
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Antineoplásicos
Limite:
Animals
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Humans
Idioma:
En
Revista:
Expert Opin Ther Pat
Assunto da revista:
TERAPEUTICA
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Estados Unidos
País de publicação:
Reino Unido