1254053-43-4

Basic information

• Product Name: ASP-2215
• Synonyms: ASP-2215;Gilteritinib;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-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;Gilteritinib (ASP2215);6-Ethyl-3-((3-methoxy-4-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)phenyl)-amino)-5-((tetrahydr;ASP2215(Gilteritinib)
• CAS NO: 1254053-43-4
• Molecular Formula: C₂₉H₄₄N₈O₃
• Molecular Weight: 552.73
• Mol File: 1254053-43-4.mol
• Article Data: 1

Chemical Properties

• Boiling Point: 696.9±55.0 °C(Predicted)
• Appearance: /
• Density: 1.242±0.06 g/cm3(Predicted)
• Storage Temp.: -20°C
• Solubility: Soluble in DMSO (25 mg/ml)
• PKA: 14.39±0.50(Predicted)
• Stability: Stable for 1 year as supplied. Solutions in DMSO may be stored at -20°C for up to 3 months.
• CAS DataBase Reference: ASP-2215(CAS DataBase Reference)
• NIST Chemistry Reference: ASP-2215(1254053-43-4)
• EPA Substance Registry System: ASP-2215(1254053-43-4)

Safety Data

• Hazardous Substances Data: 1254053-43-4(Hazardous Substances Data)

Usage

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

Description

Gilteritinib is an inhibitor of FMS-related tyrosine kinase 3 (FLT3; IC50 = 5 nM for the wild-type enzyme). 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.

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

Upstream product

• 33024-60-1 tetrahydro-2H-pyran-4-ylamine monohydrochloride 
• 2043020-03-5 3-bromo-5-chloro-6-ethylpyrazine-2-carbonitrile 

Relevant articles and documents

Synthesis method of 3,5-disubstituted-pyrazine-2-formamide compound

The invention discloses a synthesis method of a 3,5-disubstituted-pyrazine-2-formamide compound, and particularly relates to a synthesis method of a 3,5-disubstituted-pyrazine-2-formamide compound which has the excellent inhibition activity on receptor tyrosin kinase of FLT3-Axl participating in cancer cell growth. The synthesis method is characterized by comprising the following step that a compound 5 is subjected to a hydrolysis reaction, and then the 3,5-disubstituted-pyrazine-2-formamide compound is obtained. According to the method, the reaction conditions are mild, operation is easy, aftertreatment is easy and convenient, the reaction yield is significantly increased, and the method is a brand new industrialized synthesis route.