Discovery of Novel Antitumor Sulfonamides Targeting G1 Phase of the Cell Cycle

Owa, Takashi; Yoshino, Hiroshi; Okauchi, Tatsuo; Yoshimatsu, Kentaro; Ozawa, Yoichi; Sugi, Naoko Hata; Nagasu, Takeshi; Koyanagi, Nozomu; Kitoh, Kyosuke

doi:10.1021/jm9902638

Cited by 342Synthesis and biological activityCancer-related Molecular PathwaysCancer therapeutics and mechanisms

Discovery of Novel Antitumor Sulfonamides Targeting G1 Phase of the Cell Cycle

Owa, Takashi, Yoshino, Hiroshi, Okauchi, Tatsuo, Yoshimatsu, Kentaro, Ozawa, Yoichi, Sugi, Naoko Hata, Nagasu, Takeshi, Koyanagi, Nozomu +1 more·1999·Journal of Medicinal Chemistry

DOI 10.1021/jm9902638

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Abstract

Described herein is the discovery of a novel series of antitumor sulfonamides targeting G1 phase of the cell cycle. Cell cycle control in G1 phase has attracted considerable attention in recent cancer research, because many of the important proteins involved in G1 progression or G1/S transition have been found to play a crucial role in proliferation, differentiation, transformation, and programmed cell death (apoptosis). We previously reported our first antitumor sulfonamide E7010 as a novel tubulin polymerization inhibitor. Interestingly enough, continuous research on structurally related compounds led us to the finding of another class of antitumor sulfonamides that block cell cycle progression of P388 murine leukemia cells in G1 phase, but not in M phase. Of the compounds examined, N-(3-chloro-7-indolyl)-1,4-benzenedisulfonamide (E7070) showed significant antitumor activity against HCT116 human colon carcinoma both in vitro (IC(50) 0.11 microg/mL in cell proliferation assay) and in vivo (not only growth suppression but also a marked reduction of tumor size in nude mice). Because of its promising efficacy against human tumor xenografts and its unique mode of action, E7070 is currently undergoing phase I clinical trials in European countries.

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Indisulam (E7070) was identified from a systematic screen of sulfonamide variants as a promising drug candidate that targeted the G1 phase of the cell cycle.
“indisulam (originally named e7070) was identified from a systematic screen of sulfonamide variants as a promising drug candidate that targeted the g1 phase of the cell cycle (Owa et al. 1999).”
From From serendipity to strategy: molecular glue degraders in cancer therapeutics (2025) · cites this paper as Owa et al. 1999

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Authors: Owa, T., Yoshino, H., Okauchi, T., Yoshimatsu, K., Ozawa, Y., Sugi, N. H., Nagasu, T., Koyanagi, N., & Kitoh, K.
Affiliations: Eisai (Japan) (JP)
Corresponding author: Owa, Takashi
ORCID: Okauchi, Tatsuo
Ozawa, Yoichi
Sugi, Naoko Hata
Venue: Journal of Medicinal Chemistry
Publisher: American Chemical Society (ACS)
Published: 1999-08-26
Volume: 42
Issue: 19
Pages: 3789-3799
ISSN: 0022-2623 (ISSN-L)
1520-4804
DOI: 10.1021/jm9902638
OpenAlex: W2030623460
Cited by: 322
References: 28
Citations by year: 2026: 6 · 2025: 23 · 2024: 14 · 2023: 18 · 2022: 24 · 2021: 19 · 2020: 13 · 2019: 13 · 2018: 11 · 2017: 15 · 2016: 11 · 2015: 11 · 2014: 6 · 2013: 5 · 2012: 11
FWCI: 9.82
Type: journal article
Language: en
Open access: closed
Locations: Journal of Medicinal Chemistry (publishedVersion)
PubMed (publishedVersion)
Topics: Physical Sciences › Chemistry › Organic Chemistry › Synthesis and biological activity
Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cancer therapeutics and mechanisms
Keywords: G1 cell cycle arrest, tubulin polymerization inhibitors, P388 leukemia cells, tumor xenografts, anticancer drug discovery, G1/S transition
MeSH terms: Animals, Antineoplastic Agents, Flow Cytometry, Humans, Leukemia P388, Models, Chemical, Sulfonamides, Tumor Cells, Cultured, Drug Design, G1 Phase, Mice

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Discovery of Novel Antitumor Sulfonamides Targeting G1 Phase of the Cell Cycle

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