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Abstract Colorectal cancer (CRC) is one of the main malignant tumors and among the leading cause of death in cancer patients worldwide considering that recurrence and chemotherapeutic drug resistance are highly common in the advanced stage of CRC. Mutations in KRAS and BRAF occur frequently in colorectal cancers, and abnormal cell cycles caused by these mutations affect tumor progression and metastasis. Accordingly, inhibition of cell cycle has been a potential target for colorectal cancers and therefore, we have developed a new lead compound, HLS-22001. Our studies confirmed that HLS-22001 inhibited the proliferation of several cancer cells and significantly induced G2/M arrest and apoptosis of colon cancer cells and chemotherapy resistant colon cancer cells. The docking model studies showed that HLS-22001 was expected to bind to the colchicine binding site of beta-tubulin, and in fact, as a tubulin inhibitor, it had the effect of inhibiting tubulin dimerization and polymerization in the microtubule dynamics. Consistently, in xenograft mouse model, oral administration of HLS-22001 significantly suppressed tumor weight and volume without acute toxicity in mice. Collectively, these results suggest further development of HLS-22001 as a novel and promising oral drug for colorectal cancer. Citation Format: Chi-hyun Ahn, Gyu-beom Jang, Chunhwa Kim, Junho Lee, Taewon Kim, Youngeun Yang, Eunji Cho, Minchae Kim, Yun-tai Kim, Yong-Hae Han, Heebum Kang. HLS-22001 induces G2/M cell cycle arrest and apoptotic cell death via tubulin depolymerization in colon cancer abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts) ; 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84 (6Suppl): Abstract nr 507.
Ahn et al. (Fri,) studied this question.