Quizartinib HCl
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MedKoo CAT#: 200072

CAS#: 1132827-21-4 (HCl)

Description: Quizartinib, also know as AC220 and AC010220, is an orally available FLT3 / STK1 inhibitor with potential antineoplastic activity. Class III receptor tyrosine kinase inhibitor AC220 selectively inhibits class III receptor tyrosine kinases, including FMS-related tyrosine kinase 3 (FLT3/STK1), colony-stimulating factor 1 receptor (CSF1R/FMS), stem cell factor receptor (SCFR/KIT), and platelet derived growth factor receptors (PDGFRs), resulting in inhibition of ligand-independent leukemic cell proliferation and apoptosis. Mutations in FLT3, resulting in constitutive activation, are the most frequent genetic alterations in acute myeloid leukemia (AML) and occur in approximately one-third of AML cases.


Chemical Structure

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Quizartinib HCl
CAS# 1132827-21-4 (HCl)

Theoretical Analysis

MedKoo Cat#: 200072
Name: Quizartinib HCl
CAS#: 1132827-21-4 (HCl)
Chemical Formula: C29H34Cl2N6O4S
Exact Mass:
Molecular Weight: 633.589
Elemental Analysis: C, 54.98; H, 5.41; Cl, 11.19; N, 13.26; O, 10.10; S, 5.06

Price and Availability

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10.0mg USD 150.0 Ready to ship
25.0mg USD 250.0 Ready to ship
50.0mg USD 450.0 Ready to ship
100.0mg USD 650.0 Ready to ship
200.0mg USD 950.0 Ready to ship
500.0mg USD 1850.0 Ready to ship
1.0g USD 2950.0 Ready to ship
2.0g USD 4250.0 Ready to ship
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Related CAS #: 1132827-21-4 (HCl)   950769-58-1 (free base)    

Synonym: AC220; AC 220; AC-220; AC010220; AC-010220; AC 010220; AC010220.2HCl; Quizartinib; Quizartinib HCl; Quizartinib dihydrochloride..

IUPAC/Chemical Name: N-(5-tert-butyl-isoxazol-3-yl)-N'-{4-[7-(2-morpholin-4-yl-ethoxy)imidazo[2,1-b][1,3]benzothiazol-2-yl]phenyl}urea dihydrochloride

InChi Key: CVWXJKQAOSCOAB-UHFFFAOYSA-N

InChi Code: InChI=1S/C29H32N6O4S/c1-29(2,3)25-17-26(33-39-25)32-27(36)30-20-6-4-19(5-7-20)22-18-35-23-9-8-21(16-24(23)40-28(35)31-22)38-15-12-34-10-13-37-14-11-34/h4-9,16-18H,10-15H2,1-3H3,(H2,30,32,33,36)

SMILES Code: O=C(NC1=CC=C(C(N=C2SC3=C4)=CN2C3=CC=C4OCCN5CCOCC5)C=C1)NC6=NOC(C(C)(C)C)=C6

Appearance: Yellow to orange 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, not soluble in water.

Shelf Life: >5 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

Biological target: TBD
In vitro activity: Quizartinib inhibited transport of the fluorescent ABCB1 substrate DiOC2 in ABCB1-overexpressing drug-selected HL60/VCR and transfected K562/ABCB1 cells and transport of the fluorescent ABCG2 substrate pheophorbide A in ABCG2-overexpressing drug-selected 8226/MR20 and transfected K562/ABCG2 cells, in a concentration-dependent manner (Figure 1C). Of note, Quizartinib inhibition of transport occurred at lower concentrations for ABCG2 than for ABCB1, with 50% inhibition in relation to positive controls (FTC for ABCG2 and PSC-833 for ABCG2) at concentrations of approximately 0.5 µM for ABCG2, compared to 3 µM for ABCB1. Reference: PLoS One. 2013; 8(8): e71266. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3743865/
In vivo activity: The antileukemic effects of quizartinib and AC886 were assessed in a mouse xenograft model in which MV4-11 cells were injected into NOD/SCID mice. Oral administration of quizartinib or AC886 inhibited tumor growth at doses ranging from 0.3 to 10 mg/kg in a dose-dependent manner (each dose P<.0001 vs control), and both compounds had similar inhibitory effects, with 90% effective concentration (EC90) values of 0.73 and 0.92 mg/kg, respectively, without a significant impact on body weight (Figure 3A). Reference: Oncotarget. 2020 Mar 17; 11(11): 943–955. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7082118/

Preparing Stock Solutions

The following data is based on the product molecular weight 633.589 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
Formulation protocol: 1. Bhullar J, Natarajan K, Shukla S, Mathias TJ, Sadowska M, Ambudkar SV, Baer MR. The FLT3 inhibitor quizartinib inhibits ABCG2 at pharmacologically relevant concentrations, with implications for both chemosensitization and adverse drug interactions. PLoS One. 2013 Aug 14;8(8):e71266. doi: 10.1371/journal.pone.0071266. PMID: 23967177; PMCID: PMC3743865. 2. Kampa-Schittenhelm KM, Heinrich MC, Akmut F, Döhner H, Döhner K, Schittenhelm MM. Quizartinib (AC220) is a potent second generation class III tyrosine kinase inhibitor that displays a distinct inhibition profile against mutant-FLT3, -PDGFRA and -KIT isoforms. Mol Cancer. 2013 Mar 7;12:19. doi: 10.1186/1476-4598-12-19. PMID: 23497317; PMCID: PMC3637582. 3. Aikawa T, Togashi N, Iwanaga K, Okada H, Nishiya Y, Inoue S, Levis MJ, Isoyama T. Quizartinib, a selective FLT3 inhibitor, maintains antileukemic activity in preclinical models of RAS-mediated midostaurin-resistant acute myeloid leukemia cells. Oncotarget. 2020 Mar 17;11(11):943-955. doi: 10.18632/oncotarget.27489. PMID: 32215183; PMCID: PMC7082118. 4. Li J, Kumar P, Anreddy N, Zhang YK, Wang YJ, Chen Y, Talele TT, Gupta K, Trombetta LD, Chen ZS. Quizartinib (AC220) reverses ABCG2-mediated multidrug resistance: In vitro and in vivo studies. Oncotarget. 2017 Sep 16;8(55):93785-93799. doi: 10.18632/oncotarget.21078. PMID: 29212189; PMCID: PMC5706835.
In vitro protocol: 1. Bhullar J, Natarajan K, Shukla S, Mathias TJ, Sadowska M, Ambudkar SV, Baer MR. The FLT3 inhibitor quizartinib inhibits ABCG2 at pharmacologically relevant concentrations, with implications for both chemosensitization and adverse drug interactions. PLoS One. 2013 Aug 14;8(8):e71266. doi: 10.1371/journal.pone.0071266. PMID: 23967177; PMCID: PMC3743865. 2. Kampa-Schittenhelm KM, Heinrich MC, Akmut F, Döhner H, Döhner K, Schittenhelm MM. Quizartinib (AC220) is a potent second generation class III tyrosine kinase inhibitor that displays a distinct inhibition profile against mutant-FLT3, -PDGFRA and -KIT isoforms. Mol Cancer. 2013 Mar 7;12:19. doi: 10.1186/1476-4598-12-19. PMID: 23497317; PMCID: PMC3637582.
In vivo protocol: 1. Aikawa T, Togashi N, Iwanaga K, Okada H, Nishiya Y, Inoue S, Levis MJ, Isoyama T. Quizartinib, a selective FLT3 inhibitor, maintains antileukemic activity in preclinical models of RAS-mediated midostaurin-resistant acute myeloid leukemia cells. Oncotarget. 2020 Mar 17;11(11):943-955. doi: 10.18632/oncotarget.27489. PMID: 32215183; PMCID: PMC7082118. 2. Li J, Kumar P, Anreddy N, Zhang YK, Wang YJ, Chen Y, Talele TT, Gupta K, Trombetta LD, Chen ZS. Quizartinib (AC220) reverses ABCG2-mediated multidrug resistance: In vitro and in vivo studies. Oncotarget. 2017 Sep 16;8(55):93785-93799. doi: 10.18632/oncotarget.21078. PMID: 29212189; PMCID: PMC5706835.

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1: Smith CC, Zhang C, Lin KC, Lasater EA, Zhang Y, Massi E, Damon LE, Pendleton M, Bashir A, Sebra R, Perl A, Kasarskis A, Shellooe R, Tsang G, Carias H, Powell B, Burton EA, Matusow B, Zhang J, Spevak W, Ibrahim PN, Le MH, Hsu HH, Habets G, West BL, Bollag G, Shah NP. Characterizing and Overriding the Structural Mechanism of the Quizartinib-Resistant FLT3 "Gatekeeper" F691L Mutation with PLX3397. Cancer Discov. 2015 Jun;5(6):668-79. doi: 10.1158/2159-8290.CD-15-0060. Epub 2015 Apr 6. PubMed PMID: 25847190; PubMed Central PMCID: PMC4522415.

2: Zorn JA, Wang Q, Fujimura E, Barros T, Kuriyan J. Crystal structure of the FLT3 kinase domain bound to the inhibitor Quizartinib (AC220). PLoS One. 2015 Apr 2;10(4):e0121177. doi: 10.1371/journal.pone.0121177. eCollection 2015. PubMed PMID: 25837374; PubMed Central PMCID: PMC4383440.

3: Altman K, Sharata H. Catastrophic eruptive keratoacanthomas and squamous cell cancers after treatment with an FLT3 inhibitor quizartinib (AC220). Dermatol Surg. 2015 Apr;41(4):530-1. doi: 10.1097/DSS.0000000000000316. PubMed PMID: 25775444.

4: Levis M. Quizartinib for the treatment of FLT3/ITD acute myeloid leukemia. Future Oncol. 2014;10(9):1571-9. doi: 10.2217/fon.14.105. Review. PubMed PMID: 25145428.

5: Wander SA, Levis MJ, Fathi AT. The evolving role of FLT3 inhibitors in acute myeloid leukemia: quizartinib and beyond. Ther Adv Hematol. 2014 Jun;5(3):65-77. doi: 10.1177/2040620714532123. Review. PubMed PMID: 24883179; PubMed Central PMCID: PMC4031904.

6: Wolleschak D, Mack TS, Perner F, Frey S, Schnöder TM, Wagner MC, Höding C, Pils MC, Parkner A, Kliche S, Schraven B, Hebel K, Brunner-Weinzierl M, Ranjan S, Isermann B, Lipka DB, Fischer T, Heidel FH. Clinically relevant doses of FLT3-kinase inhibitors quizartinib and midostaurin do not impair T-cell reactivity and function. Haematologica. 2014 Jun;99(6):e90-3. doi: 10.3324/haematol.2014.104331. Epub 2014 Mar 14. PubMed PMID: 24633870; PubMed Central PMCID: PMC4040902.

7: Levis M. Quizartinib in acute myeloid leukemia. Clin Adv Hematol Oncol. 2013;11(9):586-8. Review. PubMed PMID: 24518522.

8: Schaab C, Oppermann FS, Klammer M, Pfeifer H, Tebbe A, Oellerich T, Krauter J, Levis M, Perl AE, Daub H, Steffen B, Godl K, Serve H. Global phosphoproteome analysis of human bone marrow reveals predictive phosphorylation markers for the treatment of acute myeloid leukemia with quizartinib. Leukemia. 2014 Mar;28(3):716-9. doi: 10.1038/leu.2013.347. Epub 2013 Nov 19. PubMed PMID: 24247654; PubMed Central PMCID: PMC3948157.

9: Ostronoff F, Estey E. The role of quizartinib in the treatment of acute myeloid leukemia. Expert Opin Investig Drugs. 2013 Dec;22(12):1659-69. doi: 10.1517/13543784.2013.842973. Epub 2013 Sep 26. Review. PubMed PMID: 24070241.

10: Cortes JE, Kantarjian H, Foran JM, Ghirdaladze D, Zodelava M, Borthakur G, Gammon G, Trone D, Armstrong RC, James J, Levis M. Phase I study of quizartinib administered daily to patients with relapsed or refractory acute myeloid leukemia irrespective of FMS-like tyrosine kinase 3-internal tandem duplication status. J Clin Oncol. 2013 Oct 10;31(29):3681-7. doi: 10.1200/JCO.2013.48.8783. Epub 2013 Sep 3. PubMed PMID: 24002496; PubMed Central PMCID: PMC3804291.

11: Bhullar J, Natarajan K, Shukla S, Mathias TJ, Sadowska M, Ambudkar SV, Baer MR. The FLT3 inhibitor quizartinib inhibits ABCG2 at pharmacologically relevant concentrations, with implications for both chemosensitization and adverse drug interactions. PLoS One. 2013 Aug 14;8(8):e71266. doi: 10.1371/journal.pone.0071266. eCollection 2013. PubMed PMID: 23967177; PubMed Central PMCID: PMC3743865.

12: Kampa-Schittenhelm KM, Heinrich MC, Akmut F, Döhner H, Döhner K, Schittenhelm MM. Quizartinib (AC220) is a potent second generation class III tyrosine kinase inhibitor that displays a distinct inhibition profile against mutant-FLT3, -PDGFRA and -KIT isoforms. Mol Cancer. 2013 Mar 7;12:19. doi: 10.1186/1476-4598-12-19. PubMed PMID: 23497317; PubMed Central PMCID: PMC3637582.

13: Gunawardane RN, Nepomuceno RR, Rooks AM, Hunt JP, Ricono JM, Belli B, Armstrong RC. Transient exposure to quizartinib mediates sustained inhibition of FLT3 signaling while specifically inducing apoptosis in FLT3-activated leukemia cells. Mol Cancer Ther. 2013 Apr;12(4):438-47. doi: 10.1158/1535-7163.MCT-12-0305. Epub 2013 Feb 14. PubMed PMID: 23412931.



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