Finally, the in vivo activity of ARQ 531 was evaluated using MOLM-13 disseminated xenograft model. The effect of SYK expression on ARQ 531 potency was evaluated using a SYK overexpressing cell line (Ba/F3 murine cells) constitutively expressing FLT3-ITD. The modulation of pro-survival kinases following ARQ 531 treatment was determined using AML cell lines. The potency of ARQ 531 was examined in vitro using FLT3 wild type and mutated (ITD) AML cell lines and primary samples. Given the superior activity of ARQ 531 in CLL, and recognition that this molecule has a broad kinase inhibition profile, we pursued its application in pre-clinical models of AML. Recently, the multi-kinase inhibitor ArQule 531 (ARQ 531) has demonstrated potent inhibition of SFK and BTK that translated to improved pre-clinical in vivo activity as compared with the irreversible BTK inhibitor ibrutinib in chronic lymphocytic leukemia (CLL) models. Several studies have demonstrated that oncogenesis in AML is enhanced by kinase signaling pathways such as Src family kinases (SFK) including Src and Lyn, spleen tyrosine kinase (SYK), and bruton's tyrosine kinase (BTK). myeloid leukemia (AML) is the most common type of adult leukemia. 8 Division of Pharmaceutics and Pharmaceutical Chemistry, The Ohio State University, Columbus, OH, USA. 7 Division of Hematology, Department of Internal Medicine, Comprehensive Cancer Center, The Ohio State University, Columbus, 455 Wiseman Hall, 400 West 12th Avenue, Columbus, OH, 43210, USA. 6 Division of Hematology, Department of Internal Medicine, Comprehensive Cancer Center, The Ohio State University, Columbus, 455 Wiseman Hall, 400 West 12th Avenue, Columbus, OH, 43210, USA.5 Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston Children's Hospital, Boston, MA, USA.3 Center for Biostatistics, Department of Biomedical Informatics, The Ohio State University, Columbus, OH, USA. ![]() 2 Division of Pharmaceutics and Pharmaceutical Chemistry, The Ohio State University, Columbus, OH, USA.1 Division of Hematology, Department of Internal Medicine, Comprehensive Cancer Center, The Ohio State University, Columbus, 455 Wiseman Hall, 400 West 12th Avenue, Columbus, OH, 43210, USA.
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