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J Med Chem ; 67(11): 9165-9172, 2024 Jun 13.
Article in English | MEDLINE | ID: mdl-38803164

ABSTRACT

Runt-related transcription factor (RUNX) proteins are considered to play various roles in cancer. Here, we evaluated the anticancer activity of Chb-M', a compound that specifically and covalently binds to the consensus sequence for RUNX family proteins, in p53-mutated non-small cell lung cancer cells. Chb-M' killed the cancer cells by inducing apoptosis. The compound showed an anticancer effect comparable to that of the clinically used drugs alectinib and ceritinib in vivo. Notably, Chb-M' extended the cancer-free survival of mice after ending treatment more effectively than did the other two drugs. The results presented here suggest that Chb-M' is an attractive candidate as an anticancer drug applicable to the treatment of non-small cell lung cancer and various other types of cancers.


Subject(s)
Antineoplastic Agents , Apoptosis , Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Tumor Suppressor Protein p53 , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/pathology , Carcinoma, Non-Small-Cell Lung/metabolism , Humans , Animals , Tumor Suppressor Protein p53/metabolism , Apoptosis/drug effects , Lung Neoplasms/drug therapy , Lung Neoplasms/pathology , Lung Neoplasms/metabolism , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/therapeutic use , Mice , Cell Line, Tumor , Mutation , Cell Proliferation/drug effects , Core Binding Factor alpha Subunits/metabolism , Mice, Nude , Xenograft Model Antitumor Assays
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