ASP-3026 / Astellas - LARVOL DELTA

AXL and SHC1 confer crizotinib resistance in patient-derived xenograft model of ALK-driven lung cancer. (PubMed, iScience) - "To discover therapeutic targets to overcome crizotinib resistance (CR), we generated patient-derived xenograft CR mice and subjected them to phosphorylation profiling, together with CR mice treated with ASP3026 or alectinib. We also found that SHC1 phosphorylation was increased in CR mice and SHC1 knockdown sensitized ALK-driven cells to crizotinib. Our study provides a new view of signaling pathways leading to CR, suggesting AXL and SHC1 as potential targets for combination therapy to overcome CR."

Journal • Preclinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • AXL

Structure-guided conversion from an anaplastic lymphoma kinase inhibitor into Plasmodium lysyl-tRNA synthetase selective inhibitors. (PubMed, Commun Biol) - "ASP3026, an anaplastic lymphoma kinase (ALK) inhibitor was recently identified as a novel Plasmodium falciparum LysRS (PfLysRS) inhibitor...However, its inhibitory activity against parasites did not improve, suggesting potential future optimization directions. This study presents a new example of derivatization of kinase inhibitors repurposed to inhibit aaRS."

Journal • Infectious Disease • Oncology • ALK

Safety and Antitumor Activity of Repeated ASP3026 Administration in Japanese Patients with Solid Tumors: A Phase I Study. (PubMed, Drugs R D) - P1 | "ASP3026 at a 200-mg dose may provide therapeutic benefit for patients with solid tumors, with a tolerable safety profile."

Clinical • Journal • P1 data • Cataract • Ewing Sarcoma • Fatigue • Oncology • Ophthalmology • Sarcoma • Solid Tumor • ALK • EML4

Inhibition of Plasmodium falciparum Lysyl-tRNA synthetase via an anaplastic lymphoma kinase inhibitor. (PubMed, Nucleic Acids Res) - "Finally, primary structure-activity relationship analyses indicated that the inhibition of PfLysRS by ASP3026 is highly structure specific. This work not only provides a new chemical scaffold with good druggability for antimalarial development but also highlights the potential for repurposing kinase-inhibiting drugs to tRNA synthetase inhibitors to treat human diseases."

Journal • Infectious Disease • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor • ALK

Dual inhibition of IGF-IR and ALK as an effective strategy to eradicate NPM-ALK T-cell lymphoma. (PubMed, J Hematol Oncol) - "Combined targeting of IGF-IR and ALK is more effective than targeting IGF-IR or ALK alone in NPM-ALK T cell lymphoma. This strategy might also limit emergence of resistance to high doses of ALK inhibitors. Therefore, it could represent a successful therapeutic approach to eradicate this aggressive lymphoma. Importantly, combined inhibition is feasible because of the clinical availability of IGF-IR and ALK inhibitors. Our findings are applicable to other types of cancer where IGF-IR and ALK are simultaneously expressed."

Journal • Non-Hodgkin’s Lymphoma • Oncology

Characterization and Thermodynamic Stability of Polymorphs of Di(arylamino) Aryl Compound ASP3026. (PubMed) - "Furthermore, the method to estimate polymorphic transition temperatures using solution calorimetry was found to be effective. The systematic characterization of ASP3026 polymorphs presented in this study enables the selective crystallization of the most stable form and design of solid formulations."

Journal • Biosimilar

Activation of IGF-1R pathway and NPM-ALK G1269A mutation confer resistance to crizotinib treatment in NPM-ALK positive lymphoma. (PubMed, Invest New Drugs) - "Although crizotinib was ineffective against cells harboring the NPM-ALK G1269A mutation, five structurally different ALK inhibitors, alectinib, ceritinib, TAE684, ASP3026 and AP26113, maintained activity against the resistant cells. Thus, we have shown that second-generation ALK tyrosine kinase inhibitors or IGF-1R inhibitors are effective in treating crizotinib-resistant tumors."

Journal