2. Academic Validation
  3. Discovery of benzimidazole-2-amide BNZ-111 as new tubulin inhibitor

Discovery of benzimidazole-2-amide BNZ-111 as new tubulin inhibitor

  • Bioorg Med Chem Lett. 2024 Sep 11:113:129953. doi: 10.1016/j.bmcl.2024.129953.
Jiyoon Jang 1,  Byumseok Koh 2,  Kwangho Lee 3
Affiliations

Affiliations

  • 1 Bio & Drug Discovery Division, Korea Research Institute of Chemical Technology, Daejeon 34114, South Korea.
  • 2 Bio & Drug Discovery Division, Korea Research Institute of Chemical Technology, Daejeon 34114, South Korea; Medicinal Chemistry & Pharmacology, Korea National University of Science & Technology, Daejeon 34113, South Korea. Electronic address: bkoh@krict.re.kr.
  • 3 Bio & Drug Discovery Division, Korea Research Institute of Chemical Technology, Daejeon 34114, South Korea; Medicinal Chemistry & Pharmacology, Korea National University of Science & Technology, Daejeon 34113, South Korea. Electronic address: kwangho@krict.re.kr.
PMID: 39270806 DOI: 10.1016/j.bmcl.2024.129953
Abstract

Methyl benzimidazole-2-carbamate anthelmintics are a class of oral drugs to treat parasitic worm infections via microtubule disruption for non-systemic indications and currently in use. In order to use for Anticancer treatment, the new benzimidazoles needs to improve solubility and pharmacokinetic parameters while maintaining its cellular potency as for systemic drug. Structure-activity-relationship on the benzimidazole is thoroughly examined and a novel benzimidazole-2 propionamide BNZ-111 is identified having good oral exposure and bioavailability in rat. Molecular docking study suggests BNZ-111 have a specific binding mode to the β subunit of curved tubulin. BNZ-111 is potent to Cancer cells and possesses good drug-like properties as oral drug. Especially, BNZ-111 is not a P-gp substrate and it demonstrates its efficacy over Paclitaxel-resistance tumor in vivo.

Keywords

Anti-cancer; Benzimidazole; Ovarian cancer; Paclitaxel-resistant; Tubulin inhibitor.

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