Gilteritinib hemifumarate

    WARNING: This product is for research use only, not for human or veterinary use.

MedKoo CAT#: 100964

CAS#: 1254053-84-3 (hemifumarate)

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.


Chemical Structure

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Gilteritinib hemifumarate
CAS# 1254053-84-3 (hemifumarate)

Theoretical Analysis

MedKoo Cat#: 100964
Name: Gilteritinib hemifumarate
CAS#: 1254053-84-3 (hemifumarate)
Chemical Formula: C62H92N16O10
Exact Mass:
Molecular Weight: 1221.52
Elemental Analysis: C, 60.96; H, 7.59; N, 18.35; O, 13.10

Price and Availability

This product is not in stock, which may be available by custom synthesis. For cost-effective reason, minimum order is 1g (price is usually high, lead time is 2~3 months, depending on the technical challenge). Quote less than 1g will not be provided. To request quote, please email to sales @medkoo.com or click below button.
Note: Price will be listed if it is available in the future.

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

Synonym: Gilteritinib hemifumarate; Gilteritinib fumarate; 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 hemifumarate

InChi Key: UJOUWHLYTQFUCU-WXXKFALUSA-N

InChi Code: InChI=1S/2C29H44N8O3.C4H4O4/c2*1-4-23-28(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;5-3(6)1-2-4(7)8/h2*5-6,19-20,22H,4,7-18H2,1-3H3,(H2,30,38)(H2,31,32,34);1-2H,(H,5,6)(H,7,8)/b;;2-1+

SMILES Code: O=C(C1=NC(CC)=C(NC2CCOCC2)N=C1NC3=CC=C(N4CCC(N5CCN(C)CC5)CC4)C(OC)=C3)N.O=C(O)/C=C/C(O)=O.O=C(C6=NC(CC)=C(NC7CCOCC7)N=C6NC8=CC=C(N9CCC(N%10CCN(C)CC%10)CC9)C(OC)=C8)N

Appearance: Solid powder

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

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

Shelf Life: >3 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).

HS Tariff Code: 2934.99.9001

Preparing Stock Solutions

The following data is based on the product molecular weight 1221.52 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL

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2: Sidaway P. Gilteritinib improves outcomes in AML. Nat Rev Clin Oncol. 2019 Nov 19. doi: 10.1038/s41571-019-0305-2. [Epub ahead of print] PubMed PMID: 31745291.

3: Smith CC, Levis MJ, Perl AE, Martinelli G, Neubauer A, Berman E, Montesinos P, Baer MR, Larson RA, Chou WC, Yokoyama H, Recher C, Yoon SS, Hill JE, Rosales M, Bahceci E. Emerging Mutations at Relapse in Patients with FLT3-Mutated Relapsed/Refractory Acute Myeloid Leukemia Who Received Gilteritinib Therapy in the Phase 3 Admiral Trial. Blood. 2019 Nov 13;134(Supplement_1):14. doi: 10.1182/blood-2019-122620. PubMed PMID: 31723984.

4: Kawase T, Nakazawa T, Eguchi T, Tsuzuki H, Ueno Y, Amano Y, Suzuki T, Mori M, Yoshida T. Effect of Fms-like tyrosine kinase 3 (FLT3) ligand (FL) on antitumor activity of gilteritinib, a FLT3 inhibitor, in mice xenografted with FL-overexpressing cells. Oncotarget. 2019 Oct 22;10(58):6111-6123. doi: 10.18632/oncotarget.27222. eCollection 2019 Oct 22. PubMed PMID: 31692922; PubMed Central PMCID: PMC6817455.

5: Perl AE, Martinelli G, Cortes JE, Neubauer A, Berman E, Paolini S, Montesinos P, Baer MR, Larson RA, Ustun C, Fabbiano F, Erba HP, Di Stasi A, Stuart R, Olin R, Kasner M, Ciceri F, Chou WC, Podoltsev N, Recher C, Yokoyama H, Hosono N, Yoon SS, Lee JH, Pardee T, Fathi AT, Liu C, Hasabou N, Liu X, Bahceci E, Levis MJ. Gilteritinib or Chemotherapy for Relapsed or Refractory FLT3-Mutated AML. N Engl J Med. 2019 Oct 31;381(18):1728-1740. doi: 10.1056/NEJMoa1902688. PubMed PMID: 31665578.

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8: Akahane D, Moriyama M, Yoshizawa S, Katagiri S, Fujimoto H, Gotoh A. Successful treatment with gilteritinib for initially FMS-like tyrosine kinase 3 gene internal tandem duplications-positive elderly refractory acute myeloid leukemia that changed into FMS-like tyrosine kinase 3 gene tyrosine kinase domain-positive after cord blood transplantation. Geriatr Gerontol Int. 2019 Oct;19(10):1063-1064. doi: 10.1111/ggi.13772. PubMed PMID: 31602758.

9: Zhao J, Song Y, Liu D. Gilteritinib: a novel FLT3 inhibitor for acute myeloid leukemia. Biomark Res. 2019 Sep 11;7:19. doi: 10.1186/s40364-019-0170-2. eCollection 2019. Review. Erratum in: Biomark Res. 2019 Oct 17;7:21. PubMed PMID: 31528345; PubMed Central PMCID: PMC6737601.

10: Saleh N. Gilteritinib Changes AML Landscape. Oncology (Williston Park). 2019 Aug 23;33(8). pii: 683729. PubMed PMID: 31469903.

11: McMahon CM, Perl AE. Gilteritinib for the treatment of relapsed and/or refractory FLT3-mutated acute myeloid leukemia. Expert Rev Clin Pharmacol. 2019 Sep;12(9):841-849. doi: 10.1080/17512433.2019.1657009. Epub 2019 Aug 27. Review. PubMed PMID: 31454267.

12: Ma J, Zhao S, Qiao X, Knight T, Edwards H, Polin L, Kushner J, Dzinic SH, White K, Wang G, Zhao L, Lin H, Wang Y, Taub JW, Ge Y. Inhibition of Bcl-2 Synergistically Enhances the Antileukemic Activity of Midostaurin and Gilteritinib in Preclinical Models of FLT3-Mutated Acute Myeloid Leukemia. Clin Cancer Res. 2019 Nov 15;25(22):6815-6826. doi: 10.1158/1078-0432.CCR-19-0832. Epub 2019 Jul 18. PubMed PMID: 31320594; PubMed Central PMCID: PMC6858954.

13: Weisberg E, Meng C, Case AE, Sattler M, Tiv HL, Gokhale PC, Buhrlage SJ, Liu X, Yang J, Wang J, Gray N, Stone RM, Adamia S, Dubreuil P, Letard S, Griffin JD. Comparison of effects of midostaurin, crenolanib, quizartinib, gilteritinib, sorafenib and BLU-285 on oncogenic mutants of KIT, CBL and FLT3 in haematological malignancies. Br J Haematol. 2019 Nov;187(4):488-501. doi: 10.1111/bjh.16092. Epub 2019 Jul 15. PubMed PMID: 31309543.

14: McMahon CM, Canaani J, Rea B, Sargent RL, Qualtieri JN, Watt CD, Morrissette JJD, Carroll M, Perl AE. Gilteritinib induces differentiation in relapsed and refractory FLT3-mutated acute myeloid leukemia. Blood Adv. 2019 May 28;3(10):1581-1585. doi: 10.1182/bloodadvances.2018029496. PubMed PMID: 31122910; PubMed Central PMCID: PMC6538870.

15: Ueno Y, Mori M, Kamiyama Y, Saito R, Kaneko N, Isshiki E, Kuromitsu S, Takeuchi M. Evaluation of gilteritinib in combination with chemotherapy in preclinical models of FLT3-ITD+ acute myeloid leukemia. Oncotarget. 2019 Apr 2;10(26):2530-2545. doi: 10.18632/oncotarget.26811. eCollection 2019 Apr 2. PubMed PMID: 31069015; PubMed Central PMCID: PMC6493465.

16: Gilteritinib Likely New Standard Care for AML. Cancer Discov. 2019 Jun;9(6):OF6. doi: 10.1158/2159-8290.CD-NB2019-046. Epub 2019 Apr 1. PubMed PMID: 30936061.

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

18: Drugs and Lactation Database (LactMed) [Internet]. Bethesda (MD): National Library of Medicine (US); 2006-. Available from http://www.ncbi.nlm.nih.gov/books/NBK535606/ PubMed PMID: 30601615.

19: 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.

20: Perl AE, Altman JK, Cortes J, Smith C, Litzow M, Baer MR, Claxton D, Erba HP, Gill S, Goldberg S, Jurcic JG, Larson RA, Liu C, Ritchie E, Schiller G, Spira AI, Strickland SA, Tibes R, Ustun C, Wang ES, Stuart R, Röllig C, Neubauer A, Martinelli G, Bahceci E, Levis M. Selective inhibition of FLT3 by gilteritinib in relapsed or refractory acute myeloid leukaemia: a multicentre, first-in-human, open-label, phase 1-2 study. Lancet Oncol. 2017 Aug;18(8):1061-1075. doi: 10.1016/S1470-2045(17)30416-3. Epub 2017 Jun 20. Erratum in: Lancet Oncol. 2017 Dec;18(12 ):e711. Lancet Oncol. 2018 Jul;19(7):e335. Lancet Oncol. 2019 Jun;20(6):e293. PubMed PMID: 28645776; PubMed Central PMCID: PMC5572576.



Additional Information

  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.

7: Elshoury A, Przespolewski A, Baron J, Wang ES. Advancing treatment of acute myeloid leukemia: the future of FLT3 inhibitors. Expert Rev Anticancer Ther. 2019 Mar;19(3):273-286. doi: 10.1080/14737140.2019.1573679. Epub 2019 Feb 6. PubMed PMID: 30681373.

8: Mims AS, Blum W. Progress in the problem of relapsed or refractory acute myeloid leukemia. Curr Opin Hematol. 2019 Mar;26(2):88-95. doi: 10.1097/MOH.0000000000000490. PubMed PMID: 30640734.

9: Drugs and Lactation Database (LactMed) [Internet]. Bethesda (MD): National Library of Medicine (US); 2006-. Available from http://www.ncbi.nlm.nih.gov/books/NBK535606/ PubMed PMID: 30601615.

10: Mixed Reviews for New AML Drugs. Cancer Discov. 2019 Feb;9(2):OF1. doi: 10.1158/2159-8290.CD-NB2018-171. Epub 2018 Dec 17. PubMed PMID: 30559267.

11: Wu M, Li C, Zhu X. FLT3 inhibitors in acute myeloid leukemia. J Hematol Oncol. 2018 Dec 4;11(1):133. doi: 10.1186/s13045-018-0675-4. Review. PubMed PMID: 30514344; PubMed Central PMCID: PMC6280371.

12: Stone RM. What FLT3 inhibitor holds the greatest promise? Best Pract Res Clin Haematol. 2018 Dec;31(4):401-404. doi: 10.1016/j.beha.2018.09.008. Epub 2018 Sep 20. Review. PubMed PMID: 30466756.

13: Medeiros BC. Is there a standard of care for relapsed AML? Best Pract Res Clin Haematol. 2018 Dec;31(4):384-386. doi: 10.1016/j.beha.2018.09.006. Epub 2018 Sep 20. Review. PubMed PMID: 30466752.

14: Katayama K, Noguchi K, Sugimoto Y. Heat shock protein 90 inhibitors overcome the resistance to Fms-like tyrosine kinase 3 inhibitors in acute myeloid leukemia. Oncotarget. 2018 Sep 28;9(76):34240-34258. doi: 10.18632/oncotarget.26045. eCollection 2018 Sep 28. PubMed PMID: 30344940; PubMed Central PMCID: PMC6188142.

15: Yamauchi T. [Incorporation of novel agents into the treatment for acute myeloid leukemia]. Rinsho Ketsueki. 2018;59(10):1988-1996. doi: 10.11406/rinketsu.59.1988. Japanese. PubMed PMID: 30305501.

16: Kato Y, Ninomiya K, Ohashi K, Tomida S, Makimoto G, Watanabe H, Kudo K, Matsumoto S, Umemura S, Goto K, Ichihara E, Ninomiya T, Kubo T, Sato A, Hotta K, Tabata M, Toyooka S, Maeda Y, Kiura K. Combined effect of cabozantinib and gefitinib in crizotinib-resistant lung tumors harboring ROS1 fusions. Cancer Sci. 2018 Oct;109(10):3149-3158. doi: 10.1111/cas.13752. Epub 2018 Sep 11. PubMed PMID: 30053332; PubMed Central PMCID: PMC6172052.

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.