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Journey of the ALK-inhibitor CH5424802 to phase II clinical trial

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Abstract

The anaplastic lymphoma kinase (ALK) receptor tyrosine kinase represents a potential therapeutic target. Specially, a variety of alterations in the ALK gene including mutations, overexpression, amplification, translocations and structural rearrangements, are involved in human cancer tumorigenesis. The second-generation ALK inhibitor CH5424802 (development code: AF802; Chugai Pharmaceutical, a subsidiary of Roche) achieves tumor regression with excellent tolerance and shows promising efficacy in patients with ALK-positive non-small cell lung cancer. CH5424802 shows good kinase selectivity, has a promising pharmacokinetics profile, and has strong antiproliferative activity in several ALK-driven tumor models. CH5424802 has also shown anti-tumor activity in mouse xenograft studies. Here, we summarize recent advances and the evidence that CH5424802 acts as an ALK inhibitor. We also discuss its potential for further development as an anticancer drug in clinical trials.

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Acknowledgments

This work was supported by KRICT’s project, SI-1304, funded by the Ministry of Knowledge Economy, Republic of Korea.

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Authors and Affiliations

  1. Cancer and Infectious Disease Research Center, Division of Drug Discovery Research, Korea Research Institute of Chemical Technology, Daejeon, 305-600, Republic of Korea

    Muhammad Latif

  2. Natural Products and Heterocyclic Research Laboratory, Department of Chemistry, Quaid-i-Azam University, Islamabad, 45320, Pakistan

    Aamer Saeed

  3. Laboratory of Translational Therapeutics, Pharmacology Research Center, Division of Drug Discovery Research, Korea Research Institute of Chemical Technology, P.O.Box 107, Yuseong-gu, Daejeon, 305-600, Republic of Korea

    Seong Hwan Kim

  4. Department of Medicinal and Pharmaceutical Chemistry, University of Science and Technology, Daejeon, 305-350, Republic of Korea

    Muhammad Latif & Seong Hwan Kim

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  1. Muhammad Latif
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  2. Aamer Saeed
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Correspondence to Seong Hwan Kim.

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Latif, M., Saeed, A. & Kim, S.H. Journey of the ALK-inhibitor CH5424802 to phase II clinical trial. Arch. Pharm. Res. 36, 1051–1054 (2013). https://doi.org/10.1007/s12272-013-0157-8

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  • DOI: https://doi.org/10.1007/s12272-013-0157-8

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