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Formula | C29H44N8O3 |
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Molecular Weight | 552.71 | CAS No. | 1254053-43-4 | |
Solubility (25°C)* | In vitro | DMSO | 4 mg/mL (7.23 mM) | |
Water | Insoluble | |||
Ethanol | Insoluble | |||
* <1 mg/ml means slightly soluble or insoluble. * Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations. * Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.) |
Description | Gilteritinib (ASP2215) is a small-molecule FLT3/AXL inhibitor with IC50 values of 0.29 nM and 0.73 nM for FLT3 and AXL, respectively. It inhibits FLT3 at an IC50 value that was approximately 800-fold more potent than the concentration required to inhibit c-KIT (230 nM). | ||||
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In vitro | Gilteritinib demonstrates potent inhibitory activity against the internal tandem duplication (FLT3-ITD) and FLT3-D835Y point mutations in cellular assays using MV4-11 and MOLM-13 cells as well as Ba/F3 cells expressing mutated FLT3. Gilteritinib decreases the phosphorylation levels of FLT3 and its downstream targets in both cellular and animal models. Gilteritinib inhibits the activity of eight of the 78 tested kinases by over 50% at concentrations of either 1 nM (FLT3, LTK, ALK, and AXL) or 5 nM (TRKA, ROS, RET, and MER)[1]. Gilteritinib treatment for 48h results in an induction of apoptosis in MV4-11 cells as determined by an increase in annexin V-positive cells. Gilteritinib also decreases the expression of anti-apoptotic proteins such as MCL-1, BCL2L10, and survivin, which are reported to be important in chemotherapy sensitivity, following 24h treatment[2]. | ||||
In vivo | In vivo, gilteritinib is distributed at high levels in xenografted tumors after oral administration. The decreased FLT3 activity and high intratumor distribution of gilteritinib translates to tumor regression and improved survival in xenograft and intra-bone marrow transplantation models of FLT3-driven AML. This antitumor activity is associated with a durable inhibition of phospho-FLT3 and phospho-STAT5. Furthermore, treatment with gilteritinib decreases the leukemic burden and prolongs survival in a mouse IBMT model. No overt toxicity is seen in mouse models treated with gilteritinib[1]. |
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Crucial role of dendritic cells in the generation of anti-tumor T-cell responses and immunogenic tumor microenvironment to suppress tumor development [ Front Immunol, 2024, 15:1200461] | PubMed: 39206204 |
LTK mutations responsible for resistance to lorlatinib in non-small cell lung cancer harboring CLIP1-LTK fusion [ Commun Biol, 2024, 7(1):412] | PubMed: 38575808 |
Pharmacological inhibition of RAS overcomes FLT3 inhibitor resistance in FLT3-ITD+ AML through AP-1 and RUNX1 [ iScience, 2024, 27(4):109576] | PubMed: 38638836 |
The impact of an additional copy of chromosome 21 in B-cell precursor acute lymphoblastic leukemia [ Genes Chromosomes Cancer, 2024, 63(1):e23217] | PubMed: 38087879 |
Lymph node medulla regulates the spatiotemporal unfolding of resident dendritic cell networks [ Immunity, 2023, 56(8):1778-1793.e10] | PubMed: 37463581 |
ABCC1 and glutathione metabolism limit the efficacy of BCL-2 inhibitors in acute myeloid leukemia [ Nat Commun, 2023, 14(1):5709] | PubMed: 37726279 |
A combinatorial therapeutic approach to enhance FLT3-ITD AML treatment [ Cell Rep Med, 2023, 10.1016/j.xcrm.2023.101286] | PubMed: 37951217 |
Allosteric SHP2 inhibition increases apoptotic dependency on BCL2 and synergizes with venetoclax in FLT3- and KIT-mutant AML [ Cell Rep Med, 2023, 4(11):101290] | PubMed: 37992684 |
ABCC1 and glutathione metabolism limit the efficacy of BCL-2 inhibitors in acute myeloid leukemia [ Nat Commun, 2023, 14(1):5709] | PubMed: 37726279 |
Transgenic IDH2R172K and IDH2R140Q zebrafish models recapitulated features of human acute myeloid leukemia [ Oncogene, 2023, 42(16):1272-1281] | PubMed: 36739363 |
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