{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"submitter":["Wang Y"],"funding":["National Natural Science Foundation of China"],"pubmed_abstract":["It is of great significance to design and synthesize novel structural inhibitors with good antitumor activity. In this study, based on rational design, a total of 42 7-azaindole derivatives as novel CDK8 inhibitors were designed and synthesized. All compounds were screened with antitumor activity and compound 6 (1-(3-((1<i>H</i>-pyrrolo[2,3-<i>b</i>]pyridin-5-yl)oxy)phenyl)-3-(<i>m</i>-tolyl)urea) exhibited the best activity, especially in acute myeloid leukemia (GI<sub>50</sub> MV4-11 = 1.97 ± 1.24 μM). This compound also exhibited excellent inhibitory activity against CDK8 (IC<sub>50</sub> = 51.3 ± 4.6 nM). Further mechanism studies shown that it could inhibit STAT5 phosphorylation and induce cell cycle arrest in the G1 phase, leading to apoptosis in acute myeloid leukemia cells. In addi"],"journal":["RSC medicinal chemistry"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11325196"],"repository":["biostudies-literature"],"pubmed_title":["Design and synthesis of 7-azaindole derivatives as potent CDK8 inhibitors for the treatment of acute myeloid leukemia."],"pmcid":["PMC11325196"],"funding_grant_id":["22377001","21977001"],"pubmed_authors":["Liu X","Zhi L","Wang Q","Zhang X","Wang Y","Lei C"],"additional_accession":[]},"is_claimable":false,"name":"Design and synthesis of 7-azaindole derivatives as potent CDK8 inhibitors for the treatment of acute myeloid leukemia.","description":"It is of great significance to design and synthesize novel structural inhibitors with good antitumor activity. In this study, based on rational design, a total of 42 7-azaindole derivatives as novel CDK8 inhibitors were designed and synthesized. All compounds were screened with antitumor activity and compound 6 (1-(3-((1<i>H</i>-pyrrolo[2,3-<i>b</i>]pyridin-5-yl)oxy)phenyl)-3-(<i>m</i>-tolyl)urea) exhibited the best activity, especially in acute myeloid leukemia (GI<sub>50</sub> MV4-11 = 1.97 ± 1.24 μM). This compound also exhibited excellent inhibitory activity against CDK8 (IC<sub>50</sub> = 51.3 ± 4.6 nM). Further mechanism studies shown that it could inhibit STAT5 phosphorylation and induce cell cycle arrest in the G1 phase, leading to apoptosis in acute myeloid leukemia cells. In addi","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Jul","modification":"2026-06-02T09:15:55.988Z","creation":"2024-12-03T19:35:55.121Z"},"accession":"S-EPMC11325196","cross_references":{"pubmed":["39157854"],"doi":["10.1039/d4md00465e"]}}