| Identification | Back Directory | [Name]
ASP-2215 | [CAS]
1254053-43-4 | [Synonyms]
CS-2849
ASP-2215
mobcertinib
Gilteritinib
ASP2215(Gilteritinib)
Gilteritinib (ASP2215)
Gilteritinib(free base)
6-Ethyl-3-((3-methoxy-4-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)phenyl)-amino)-5-((tetrahydr
6-Ethyl-3-[[3-methoxy-4-[4-(4-methyl-1-piperazinyl)-1-piperidinyl]phenyl]amino]-5-[(tetrahydro-2H-pyran-4-yl)amino]-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
2-Pyrazinecarboxamide, 6-ethyl-3-[[3-methoxy-4-[4-(4-methyl-1-piperazinyl)-1-piperidinyl]phenyl]amino]-5-[(tetrahydro-2H-pyran-4-yl)amino]- | [Molecular Formula]
C29H44N8O3 | [MDL Number]
MFCD28144685 | [MOL File]
1254053-43-4.mol | [Molecular Weight]
552.71 |
| Questions And Answer | Back Directory | [Physical Form]
Pale-yellow to Yellow-brown Solid | [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 |
| Chemical Properties | Back Directory | [Melting point ]
>157°C (dec.) | [Boiling point ]
696.9±55.0 °C(Predicted) | [density ]
1.242±0.06 g/cm3(Predicted) | [storage temp. ]
-20°C | [solubility ]
Soluble in DMSO (25 mg/ml) | [form ]
solid | [pka]
14.39±0.50(Predicted) | [color ]
Off-white to pale pink | [Stability:]
Stable for 1 year as supplied. Solutions in DMSO may be stored at -20°C for up to 3 months. |
| Hazard Information | Back Directory | [Description]
Gilteritinib is an inhibitor of FMS-related tyrosine kinase 3 (FLT3; IC50 = 5 nM for the wild-type enzyme).1 It inhibits mutant forms of FLT3, including FLT3 with the internal tandem duplication mutation (FLT3-ITD), FLT3-ITD expressing the F691L mutation, and FLT3 with various tyrosine kinase domain mutations (FLT3-TKD; IC50s =1.4-1.8, 12.2, and 0.7-2 nM, respectively). Gilteritinib also inhibits Axl and c-Kit with IC50 values of 41 and 102 nM, respectively. It decreases the viability of blast cells isolated from patients with relapsed acute myeloid leukemia (AML) in a concentration-dependent manner. Formulations containing gilteritinib have been used in the treatment of AML. | [Uses]
Gilteritinib is an AXL inhibitor in cancer. | [Definition]
ChEBI: Gilteritinib is a member of the class of pyrazines that is pyrazine-2-carboxamide which is substituted by {3-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl}nitrilo, (oxan-4-yl)nitrilo and ethyl groups at positions 3,5 and 6, respectively. It is a potent inhibitor of FLT3 and AXL tyrosine kinase receptors (IC50 = 0.29 nM and 0.73 nM, respectively). Approved by the FDA for the treatment of acute myeloid leukemia in patients who have a FLT3 gene mutation. It has a role as an apoptosis inducer, an EC 2.7.10.1 (receptor protein-tyrosine kinase) inhibitor and an antineoplastic agent. It is a N-methylpiperazine, a member of piperidines, a secondary amino compound, a monomethoxybenzene, a member of pyrazines, a primary carboxamide, an aromatic amine and a member of oxanes. | [Brand name]
Xospata | [General Description]
Class: receptor tyrosine kinase;
Treatment: AML, SM;
Other name: ASP-2215;
Oral bioavailability > 61%;
Elimination half-life = 113 h;
Protein binding = 94% | [target]
FLT3, AXL | [References]
Lee et al. (2017) Preclinical studies of gilteritinib, a next-generation FLT3 inhibitor; Blood?129 257
Thomas et al. (2021) Gilteritinib Inhibits Glutamine Uptake and Utilization in FLT-3-ITD-Positive AML; Cancer Ther.?20 2207 |
|
|