Development of small molecule inhibitors targeting RNA helicase DHX33 as anti-cancer agents Article published in BMCL

On October 9, 2023 Kaiyue Life reported the company and other institutions jointly published a paper titled "Development of small molecule inhibitors targeting RNA helicase DHX33 as anti-cancer agents" in the classic journal of medicinal chemistry, Bioorganic and Medicinal Chemistry Letters (BMCL) (Press release, KeYe Life Technologies, OCT 9, 2023, View Source;article_id=84 [SID1234644610]).

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Recently, a collaborative paper titled "Development of small molecule inhibitors targeting RNA helicase DHX33 as anti-cancer agents" co-authored by Kaiyue Life Sciences, the University of Macau, Southern University of Science and Technology, and Heya Pharmaceuticals was published online in BMCL, a long-established journal of medicinal chemistry.

The RNA helicase DHX33 has been identified as a key player in promoting cancer development. Genetic deletion of DHX33 significantly blocks tumorigenesis. Importantly, its helicase activity was found to be critical for exerting cellular functions. In this study, a helicase-based high-throughput screening (HTS) technique was used to discover DHX33 inhibitors from the Chembridge chemical library containing 15,000 small molecules. We discovered a lead compound containing a benzimidazole ring that showed some selectivity for DHX33. Further structural optimization led to the design and synthesis of a series of mimetic inhibitors. Considering the potential role of DHX33 in cancer development, we evaluated these compounds based on their cytotoxic activity against U251-MG cancer cells in vitro. Among them, compound IVa (KY386) was identified as a selective inhibitor of DHX33 helicase with strong anticancer activity and moderate metabolic stability. These results support the important role of DHX33 inhibitors in the development of novel anticancer drugs.