Technology Bundle ID
TAB-3588

Treatment of Acute Myeloid Leukemia (AML) with the Multi-kinase FLT3-IRAK1/4 Inhibitor, NCGC1481, to Avoid Adaptive Resistance

Applications
Linked ID
E-055-2020-0
Lead Inventors
Craig Thomas (NCATS)
Co-Inventors
Jian-kang Jiang (NCATS)
ICs
This technology includes the identification and use of a novel small molecule, NCGC1481, to inhibit both the FLT3 and IRAK1/4 kinase pathways for treating acute myeloid leukemia (AML). An activating mutation of the FMS-like receptor kinase 3 (FMT3) occurs in approximately 25% of AML cases. Consequently, FLT3 inhibitors (FLT3i) have a good initial clinical response, however patients relapse with FLT3i-resistance. This adaptive resistance following FLT3i treatment is partially conferred by activation of the IRAK1/4 kinase complex. Given the challenges of achieving multi-drug combination regimens, a high-throughput screen was performed to identify compounds that could inhibit both FLT3i and IRAK1/4 kinases simultaneously. The multi-kinase FLT3-IRAK1/4 inhibitor NCGC1481eliminated adaptive resistant FLT3-ITD AML cells in vitro and in vivo, and displayed superior efficacy as compared to current targeted FLT3 therapies.
Commercial Applications
Further clinical work with NCGC1481could support the clinical use of the multi-kinase FLT3-IRAK1/4 inhibitor for the treatment of acute myeloid leukemia (AML).
Competitive Advantages
Treatment of acute myeloid leukemia (AML) with the multi-kinase FLT3-IRAK1/4 inhibitor, NCGC1481, may overcome adaptive resistance in therapy.

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