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    1year
    Comparative Atomistic Insights on Apo and ATP-I1171N/S/T in Nonsmall-Cell Lung Cancer. (PubMed, ACS Omega)
    ALK inhibitors first-line crizotinib, second-line ceritinib, and alectinib are effective against NSCLC patients with these rearrangements. Based on the Y1278-C1097 H-bond and E1167-K1150 salt bridge interaction, I1171N strongly promotes the constitutively active kinase independent of ATP. This structural mechanism study will aid in understanding the oncogenic activity of ALK and the basis for improving the ALK inhibitors.
    Journal
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    ALK (Anaplastic lymphoma kinase) • EML4 (EMAP Like 4)
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    ALK rearrangement • EML4-ALK fusion • ALK fusion • ALK mutation • ALK I1171N • ALK I1171 • ALK I1171S • EML4-ALK I1171S
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    Xalkori (crizotinib) • Alecensa (alectinib) • Zykadia (ceritinib)
    over2years
    First-in-human phase I results of APG-2449, a novel FAK and third-generation ALK/ ROS1 tyrosine kinase inhibitor (TKI), in patients (pts) with second-generation TKI-resistant ALK/ROS1+ non–small cell lung cancer (NSCLC) or mesothelioma. (ASCO 2022)
    Another pt with the G1202R mutation following alectinib treatment had tumor shrinkage of 27.9%. APG-2449 has a favorable safety and PK profile and was well tolerated in 84 subjects. Preliminary efficacy was observed in pts whose disease was resistant to second-generation TKIs, especially among those with brain metastases, and in TKI-naïve pts. Biomarker data indicated potential target engagement on FAK and immunomodulatory effects of APG-2449.
    Clinical • P1 data
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    ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • IFNG (Interferon, gamma)
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    ALK mutation • ALK G1202R • ALK C1156Y • ALK G1269A • ALK I1171 • ALK L1196M • ALK E1210K • ALK I1171S • ALK V1180L
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    Alecensa (alectinib) • APG-2449