Synthesis, growth inhibitory activity against tumor cells, and structure-activity relationship of CGK733 and its analogs

Yuta Inagaki; Kohki Hashimoto; Shinnosuke Wakamori; Ryo Katsuta; Arata Yajima; Daisuke Kaida; Ken Ishigami

doi:10.1093/bbb/zbae047

Synthesis, growth inhibitory activity against tumor cells, and structure-activity relationship of CGK733 and its analogs

Yuta Inagaki, Kohki Hashimoto, Shinnosuke Wakamori, Ryo Katsuta, Arata Yajima, Daisuke Kaida^*, Ken Ishigami^*

^*Corresponding author for this work

Gene Expression and Regulation

Research output: Contribution to journal › Article › peer-review

Abstract

CGK733 was reported as a compound that inhibited ATM/ATR kinase activities and blocked their checkpoint signaling pathways with great selectivity. However, this paper was subsequently retracted, and the truth about the activity of CGK733 remains unclear. We synthesized various analogs of CGK733 with a modification of the carboxylic acid moiety and/or the aniline derivative moiety to accumulate knowledge of the structure-activity relationship of this compound. Growth inhibitory activity of CGK733 and novel 35 analogs against HeLa S3 cells was evaluated, and the structure-activity relationship revealed that analogs with the 2-naphthyl or 4-fluorophenyl group instead of the benzhydryl group have activity comparable to CGK733 and that the 3-nitro group on the aniline moiety significantly affects the activity.

Original language	English
Pages (from-to)	747-758
Number of pages	12
Journal	Bioscience, biotechnology, and biochemistry
Volume	88
Issue number	7
DOIs	https://doi.org/10.1093/bbb/zbae047
State	Published - 2024/07/01

Keywords

CGK733
growth inhibitory activity
structure-activity relationship
synthesis

ASJC Scopus subject areas

General Medicine

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10.1093/bbb/zbae047

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title = "Synthesis, growth inhibitory activity against tumor cells, and structure-activity relationship of CGK733 and its analogs",

abstract = "CGK733 was reported as a compound that inhibited ATM/ATR kinase activities and blocked their checkpoint signaling pathways with great selectivity. However, this paper was subsequently retracted, and the truth about the activity of CGK733 remains unclear. We synthesized various analogs of CGK733 with a modification of the carboxylic acid moiety and/or the aniline derivative moiety to accumulate knowledge of the structure-activity relationship of this compound. Growth inhibitory activity of CGK733 and novel 35 analogs against HeLa S3 cells was evaluated, and the structure-activity relationship revealed that analogs with the 2-naphthyl or 4-fluorophenyl group instead of the benzhydryl group have activity comparable to CGK733 and that the 3-nitro group on the aniline moiety significantly affects the activity.",

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author = "Yuta Inagaki and Kohki Hashimoto and Shinnosuke Wakamori and Ryo Katsuta and Arata Yajima and Daisuke Kaida and Ken Ishigami",

note = "Publisher Copyright: {\textcopyright} The Author(s) 2024. Published by Oxford University Press on behalf of Japan Society for Bioscience, Biotechnology, and Agrochemistry.",

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doi = "10.1093/bbb/zbae047",

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T1 - Synthesis, growth inhibitory activity against tumor cells, and structure-activity relationship of CGK733 and its analogs

AU - Inagaki, Yuta

AU - Hashimoto, Kohki

AU - Wakamori, Shinnosuke

AU - Katsuta, Ryo

AU - Yajima, Arata

AU - Kaida, Daisuke

AU - Ishigami, Ken

N1 - Publisher Copyright: © The Author(s) 2024. Published by Oxford University Press on behalf of Japan Society for Bioscience, Biotechnology, and Agrochemistry.

PY - 2024/7/1

Y1 - 2024/7/1

N2 - CGK733 was reported as a compound that inhibited ATM/ATR kinase activities and blocked their checkpoint signaling pathways with great selectivity. However, this paper was subsequently retracted, and the truth about the activity of CGK733 remains unclear. We synthesized various analogs of CGK733 with a modification of the carboxylic acid moiety and/or the aniline derivative moiety to accumulate knowledge of the structure-activity relationship of this compound. Growth inhibitory activity of CGK733 and novel 35 analogs against HeLa S3 cells was evaluated, and the structure-activity relationship revealed that analogs with the 2-naphthyl or 4-fluorophenyl group instead of the benzhydryl group have activity comparable to CGK733 and that the 3-nitro group on the aniline moiety significantly affects the activity.

AB - CGK733 was reported as a compound that inhibited ATM/ATR kinase activities and blocked their checkpoint signaling pathways with great selectivity. However, this paper was subsequently retracted, and the truth about the activity of CGK733 remains unclear. We synthesized various analogs of CGK733 with a modification of the carboxylic acid moiety and/or the aniline derivative moiety to accumulate knowledge of the structure-activity relationship of this compound. Growth inhibitory activity of CGK733 and novel 35 analogs against HeLa S3 cells was evaluated, and the structure-activity relationship revealed that analogs with the 2-naphthyl or 4-fluorophenyl group instead of the benzhydryl group have activity comparable to CGK733 and that the 3-nitro group on the aniline moiety significantly affects the activity.

KW - CGK733

KW - growth inhibitory activity

KW - structure-activity relationship

KW - synthesis

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U2 - 10.1093/bbb/zbae047

DO - 10.1093/bbb/zbae047

M3 - 学術論文

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SN - 0916-8451

VL - 88

SP - 747

EP - 758

JO - Bioscience, biotechnology, and biochemistry

JF - Bioscience, biotechnology, and biochemistry

IS - 7

ER -

Synthesis, growth inhibitory activity against tumor cells, and structure-activity relationship of CGK733 and its analogs

Abstract

Keywords

ASJC Scopus subject areas

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