Gilteritinib
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MedKoo CAT#: 206139

CAS#: 1254053-43-4 (free base)

Description: Gilteritinib, also known as ASP2215, is a potent FLT3/AXL inhibitor, which showed potent antileukemic activity against AML with either or both FLT3-ITD and FLT3-D835 mutations. In invitro, among the 78 tyrosine kinases tested, ASP2215 inhibited FLT3, LTK, 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, the inhibition of which is linked to a potential risk of myelosuppression. ASP2215 inhibited the growth of MV4-11 cells, which harbor FLT3-ITD, with an IC50 value of 0.92 nM, accompanied with inhibition of pFLT3, pAKT, pSTAT5, pERK, and pS6. ASP2215 decreased tumor burden in bone marrow and prolonged the survival of mice intravenously transplanted with MV4-11 cells. ASP2215 may have potential use in treating AML.


Price and Availability

Size
Price

25mg
USD 150
200mg
USD 850
Size
Price

50mg
USD 250
Size
Price

100mg
USD 450

Gilteritinib (ASP2215), purity > 98%, is in stock. The same day shipping out after order is received.


Chemical Structure

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Theoretical Analysis

MedKoo Cat#: 206139
Name: Gilteritinib
CAS#: 1254053-43-4 (free base)
Chemical Formula: C29H44N8O3
Exact Mass: 552.35364
Molecular Weight: 552.71
Elemental Analysis: C, 63.02; H, 8.02; N, 20.27; O, 8.68


Related CAS #: 1254053-43-4 (free base)   1254053-84-3 (hemifumarate)    

Synonym: ASP-2215; ASP2215; ASP 2215; Gilteritinib.

IUPAC/Chemical Name: 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.

InChi Key: GYQYAJJFPNQOOW-UHFFFAOYSA-N

InChi Code: InChI=1S/C29H44N8O3/c1-4-23-28(31-20-9-17-40-18-10-20)34-29(26(33-23)27(30)38)32-21-5-6-24(25(19-21)39-3)37-11-7-22(8-12-37)36-15-13-35(2)14-16-36/h5-6,19-20,22H,4,7-18H2,1-3H3,(H2,30,38)(H2,31,32,34)

SMILES Code: O=C(C1=NC(CC)=C(NC2CCOCC2)N=C1NC3=CC=C(N4CCC(N5CCN(C)CC5)CC4)C(OC)=C3)N


Technical Data

Appearance:
Yellow solid powder

Purity:
>98% (or refer to the Certificate of Analysis)

Safety Data Sheet (MSDS):

Shipping Condition:
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition:
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility:
Soluble in DMSO, not in water

Shelf Life:
>2 years if stored properly

Drug Formulation:
This drug may be formulated in DMSO

Stock Solution Storage:
0 - 4 C for short term (days to weeks), or -20 C for long term (months).

Harmonized System Code:
2934.99.90.01


Additional Information

  
 
 
 


References

  1: Gilteritinib Likely New Standard Care for AML. Cancer Discov. 2019 Apr 1. doi: 10.1158/2159-8290.CD-NB2019-046. [Epub ahead of print] PubMed PMID: 30936061.

2: Chang YT, Hernandez D, Alonso S, Gao M, Su M, Ghiaur G, Levis MJ, Jones RJ. Role of CYP3A4 in bone marrow microenvironment-mediated protection of FLT3/ITD AML from tyrosine kinase inhibitors. Blood Adv. 2019 Mar 26;3(6):908-916. doi: 10.1182/bloodadvances.2018022921. PubMed PMID: 30898762; PubMed Central PMCID: PMC6436013.

3: Tiong IS, Wei AH. New drugs creating new challenges in acute myeloid leukemia. Genes Chromosomes Cancer. 2019 Mar 12. doi: 10.1002/gcc.22750. [Epub ahead of print] Review. PubMed PMID: 30861214.

4: Short NJ, Kantarjian H, Ravandi F, Daver N. Emerging treatment paradigms with FLT3 inhibitors in acute myeloid leukemia. Ther Adv Hematol. 2019 Feb 15;10:2040620719827310. doi: 10.1177/2040620719827310. eCollection 2019. Review. PubMed PMID: 30800259; PubMed Central PMCID: PMC6378516.

5: Dhillon S. Gilteritinib: First Global Approval. Drugs. 2019 Feb;79(3):331-339. doi: 10.1007/s40265-019-1062-3. PubMed PMID: 30721452.

6: Wang Y, Xing L, Ji Y, Ye J, Dai Y, Gu W, Ai J, Song Z. Discovery of a potent tyrosine kinase AXL inhibitor bearing the 3-((2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-yl)amino)pyrazine core. Bioorg Med Chem Lett. 2019 Mar 15;29(6):836-838. doi: 10.1016/j.bmcl.2019.01.018. Epub 2019 Jan 21. PubMed PMID: 30685094.

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17: Usuki K, Sakura T, Kobayashi Y, Miyamoto T, Iida H, Morita S, Bahceci E, Kaneko M, Kusano M, Yamada S, Takeshita S, Miyawaki S, Naoe T. Clinical profile of gilteritinib in Japanese patients with relapsed/refractory acute myeloid leukemia: An open-label phase 1 study. Cancer Sci. 2018 Oct;109(10):3235-3244. doi: 10.1111/cas.13749. PubMed PMID: 30039554; PubMed Central PMCID: PMC6172068.

18: Cucchi DGJ, Denys B, Kaspers GJL, Janssen JJWM, Ossenkoppele GJ, de Haas V, Zwaan CM, van den Heuvel-Eibrink MM, Philippé J, Csikós T, Kwidama Z, de Moerloose B, de Bont ESJM, Lissenberg-Witte BI, Zweegman S, Verwer F, Vandepoele K, Schuurhuis GJ, Sonneveld E, Cloos J. RNA-based FLT3-ITD allelic ratio is associated with outcome and ex vivo response to FLT3 inhibitors in pediatric AML. Blood. 2018 May 31;131(22):2485-2489. doi: 10.1182/blood-2017-12-819508. Epub 2018 Apr 18. PubMed PMID: 29669779.

19: Levis MJ, Perl AE, Altman JK, Gocke CD, Bahceci E, Hill J, Liu C, Xie Z, Carson AR, McClain V, Stenzel TT, Miller JE. A next-generation sequencing-based assay for minimal residual disease assessment in AML patients with FLT3-ITD mutations. Blood Adv. 2018 Apr 24;2(8):825-831. doi: 10.1182/bloodadvances.2018015925. PubMed PMID: 29643105; PubMed Central PMCID: PMC5916006.

20: Okada K, Nogami A, Ishida S, Akiyama H, Chen C, Umezawa Y, Miura O. FLT3-ITD induces expression of Pim kinases through STAT5 to confer resistance to the PI3K/Akt pathway inhibitors on leukemic cells by enhancing the mTORC1/Mcl-1 pathway. Oncotarget. 2017 Dec 4;9(10):8870-8886. doi: 10.18632/oncotarget.22926. eCollection 2018 Feb 6. PubMed PMID: 29507660; PubMed Central PMCID: PMC5823622.