Gilteritinib
Modify Date: 2024-01-02 17:38:33
Gilteritinib structure
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Common Name | Gilteritinib | ||
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| CAS Number | 1254053-43-4 | Molecular Weight | 552.711 | |
| Density | 1.2±0.1 g/cm3 | Boiling Point | 696.9±55.0 °C at 760 mmHg | |
| Molecular Formula | C29H44N8O3 | Melting Point | N/A | |
| MSDS | N/A | Flash Point | 375.3±31.5 °C | |
Use of GilteritinibGilteritinib is a potent FLT3/AXL inhibitor with IC50s of 0.29 nM/0.73 nM, respectively. |
| Name | Gilteritinib |
|---|---|
| Synonym | More Synonyms |
| Description | Gilteritinib is a potent FLT3/AXL inhibitor with IC50s of 0.29 nM/0.73 nM, respectively. |
|---|---|
| Related Catalog | |
| Target |
IC50: 0.29 nM (FLT3)[1] IC50: 0.35 nM (LTK), 0.73 nM (AXL), 1.2 nM (EML4-ALK), 230 nM (c-KIT)[2] |
| In Vitro | Of the 78 tyrosine kinases tested, Gilteritinib (ASP2215) inhibits FLT3, leukocyte tyrosine kinase (LTK), anaplastic lymphoma kinase (ALK), and AXL kinases by over 50% at 1 nM with an IC50 value of 0.29 nM for FLT3, approximately 800-fold more potent than for c-KIT[1]. 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). The IC50s are 0.29 nM for FLT3 and 0.73 nM for AXL. Gilteritinib inhibits FLT3 at an IC50 that is approximately 800-fold more potent than the concentration required to inhibit c-KIT (230 nM). The antiproliferative activity of Gilteritinib is evaluated against MV4-11 and MOLM-13 cells, which endogenously express FLT3-ITD. After 5 days of treatment, Gilteritinib inhibits the growth of MV4-11 and MOLM-13 cells with mean IC50s of 0.92 nM (95% CI: 0.23-3.6 nM) and 2.9 nM (95% CI: 1.4-5.8 nM), respectively. Growth suppression of MV4-11 cells is accompanied by inhibition of FLT3 phosphorylation. Relative to vehicle control cells, phosphorylated FLT3 levels are 57%, 8%, and 1% after 2 h of treatment with 0.1 nM, 1 nM, and 10 nM Gilteritinib, respectively. In addition, doses as low as 0.1 nM or 1 nM result in the suppression of phosphorylated ERK, STAT5, and AKT, all of which are downstream targets of FLT3 activation. To investigate the effects of Gilteritinib on AXL inhibition, MV4-11 cells that expressed exogenous AXL are treated with Gilteritinib. At concentrations of 1 nM, 10 nM, and 100 nM for 4 h, Gilteritinib treatment decreases phosphorylated AXL levels by 38%, 29%, and 22%, respectively[2]. |
| In Vivo | In MV4-11 xenografted-mice, the concentration of Gilteritinib (ASP2215) in tumors is more than 20-fold higher than that in plasma with oral administration of Gilteritinib at 10 mg/kg for 4 days. Treatment of Gilteritinib for 28 days results in dose-dependent inhibition of MV4-11 tumor growth and induces complete tumor regression at more than 6 mg/kg. Further, Gilteritinib decreases tumor burden in bone marrow and prolonged the survival of mice intravenously transplanted with MV4-11 cells[1]. |
| Kinase Assay | The kinase inhibitory activity of Gilteritinib is tested against a panel of 78 tested kinases using ATP concentrations that are approximately equal to the Km value for each kinase in a TK-ELISA or off-chip mobility shift assay. Initially, two concentrations of Gilteritinib (1 nM and 5 nM) are tested to assess each compound’s inhibitory effect on TK activity. Further studies are then conducted using a dose range of Gilteritinib to determine IC50 values for kinases in which activity is inhibited by >50% with 1 nM Gilteritinib as well as for c-KIT. TK-ELISA and MSA assays are used to conduct IC50 studies for FLT3, LTK, AXL, and c-KIT; the HTRF KinEASE-TK assay is performed to assess the IC50 value of echinoderm microtubule-associated protein-like 4-ALK (EML4-ALK)[2]. |
| Cell Assay | The effect of Gilteritinib on MV4-11 and MOLM-13 cells is assessed using the CellTiter-Glo Luminescent Cell Viability Assay. Subsequent studies are conducted to examine the effect of Gilteritinib and Quizartinib on Ba/F3 cells expressing either FLT3-ITD, FLT3-D835Y, FLT3-ITD-D835Y, FLT3-ITD-F691 L, or FLT3-ITD-F691I. MV4-11 and MOLM-13 cells are treated with DMSO or increasing concentrations of Gilteritinib (0.01, 0.1, 1, 10, and 100 nM) for 5 days, and cell viability is measured using CellTiter-Glo[2]. |
| Animal Admin | Mice[1] Antitumor activity is evaluated in nude mice transplanted with MV4-11 AML cells. The pharmacokinetics in xenografted mice is also investigated. MV4-11 xenografted-mice are treated with oral administration of Gilteritinib at 10 mg/kg for 4 days. Treatment of Gilteritinib for 28 days results in dose-dependent inhibition of MV4-11 tumor growth and induces complete tumor regression at more than 6 mg/kg[1]. |
| References |
| Density | 1.2±0.1 g/cm3 |
|---|---|
| Boiling Point | 696.9±55.0 °C at 760 mmHg |
| Molecular Formula | C29H44N8O3 |
| Molecular Weight | 552.711 |
| Flash Point | 375.3±31.5 °C |
| Exact Mass | 552.353638 |
| PSA | 121.11000 |
| LogP | 4.35 |
| Vapour Pressure | 0.0±2.2 mmHg at 25°C |
| Index of Refraction | 1.627 |
| Storage condition | -20℃ |
| 2-Pyrazinecarboxamide, 6-ethyl-3-[[3-methoxy-4-[4-(4-methyl-1-piperazinyl)-1-piperidinyl]phenyl]amino]-5-[(tetrahydro-2H-pyran-4-yl)amino]- |
| 6-Ethyl-3-({3-methoxy-4-[4-(4-methyl-1-piperazinyl)-1-piperidinyl]phenyl}amino)-5-(tetrahydro-2H-pyran-4-ylamino)-2-pyrazinecarboxamide |
| 6-ethyl-3-({3-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl}amino)-5-[(tetrahydro-2H-pyran-4-yl)amino]pyrazine-2-carboxamide |
| ASP2215 |
| 6-ethyl-3-{3-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]anilino}-5-(oxan-4-ylamino)pyrazine-2-carboxamide |
| 6-ethyl-3-({3-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl}amino)-5-(tetrahydro-2H-pyran-4-ylamino)pyrazine-2-carboxamide |
- DC Chemicals Limited
- China
- Product Name: Gilteritinib(ASP2215)
- Price: $700.0/100mg $1300.0/250mg $2500.0/1g
- Purity: 98.0%
- Stocking Period: 3 Day
- Contact: Tony Cao
- Zhejiang Hangyu API Co., Ltd
- China
- Product Name: ASP-2215
- Price: ￥Inquiry/1kg
- Purity: 99.5%
- Stocking Period: Inquiry
- Contact: Vinnie
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Price: $122/10mM*1mLinDMSO
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