Structure of Quizartinib
CAS No.: 950769-58-1
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The BI-3802 was designed by Boehringer Ingelheim and could be obtained free of charge through the Boehringer Ingelheim open innovation portal opnMe.com, associated with its negative control.
Quizartinib (AC220) is an orally active, highly selective, and potent second-generation type II FLT3 tyrosine kinase inhibitor with a Kd of 1.6 nM.Quizartinib inhibits wild-type FLT3 and FLT3-ITD autophosphorylation in MV4-11 cells with IC50 values of 4.2 and 1.1 nM, respectively, and can be linked to the VHL ligand via an optimized linker to form a PROTAC FLT3 degrader, inducing apoptosis.
Synonyms: AC220
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CAS No. : | 950769-58-1 |
Formula : | C29H32N6O4S |
M.W : | 560.67 |
SMILES Code : | O=C(NC1=CC=C(C2=CN3C(SC4=CC(OCCN5CCOCC5)=CC=C34)=N2)C=C1)NC6=NOC(C(C)(C)C)=C6 |
Synonyms : |
AC220
|
MDL No. : | MFCD18074524 |
InChI Key : | CVWXJKQAOSCOAB-UHFFFAOYSA-N |
Pubchem ID : | 24889392 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Description |
Quizartinib (AC220) is an orally bioavailable, highly selective, and potent second-generation type II FLT3 tyrosine kinase inhibitor, with a Kd of 1.6 nM. It effectively inhibits both wild-type FLT3 and FLT3-ITD autophosphorylation in MV4-11 cells, with IC50 values of 4.2 and 1.1 nM, respectively. Additionally, Quizartinib can be conjugated to the VHL ligand through an optimized linker to develop a PROTAC FLT3 degrader. Furthermore, Quizartinib induces apoptosis[1].
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Target |
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In Vitro:
Concentration | Treated Time | Description | References |
MV4;11 | 10 nM | 24 h | To evaluate the effect of FLT3 inhibition on BCL-XL and MCL-1 protein expression. Results showed that quizartinib significantly reduced BCL-XL and MCL-1 protein expression but did not alter BCL-2 expression. | PMC8017817 |
Molm13 | 10 nM | 24 h | To evaluate the effect of FLT3 inhibition on BCL-XL and MCL-1 protein expression. Results showed that quizartinib significantly reduced BCL-XL and MCL-1 protein expression but did not alter BCL-2 expression. | PMC8017817 |
FLT3(ITD); TET2mut AML cells | 50 nM | 3-5 days | To test the effect of Quizartinib on FLT3(ITD); TET2mut AML cells in BMM conditions, results showed that Quizartinib inhibited the clonogenic activity of cells in BMM. | PMC7578922 |
FLT3(ITD); Tet2−/− AML-like cells | 100 nM | 3-5 days | To test the effect of Quizartinib on FLT3(ITD); Tet2−/− AML-like cells in BMM conditions, results showed that Quizartinib inhibited the clonogenic activity of cells in BMM. | PMC7578922 |
FLT3ITD;NPM1mut AML cells | 10 nM | 72 h | To assess the sensitivity of FLT3ITD;NPM1mut AML cells to Quizartinib, results showed that the sensitivity to Quizartinib was not affected by TET2mut and DNMT3Amut. | PMC8487956 |
MV4-11 cells | 0.16 nM | 48 h | To evaluate the growth inhibitory effect of Foretinib on MV4-11 cells carrying FLT3-ITD mutations, results showed that Foretinib effectively inhibited the growth of MV4-11 cells with an IC50 value of 0.16 nM | PMC10940854 |
MOLM13 cells | 0.89 nM | 48 h | To evaluate the growth inhibitory effect of Foretinib on MOLM13 cells carrying FLT3-ITD mutations, results showed that Foretinib effectively inhibited the growth of MOLM13 cells with an IC50 value of 0.89 nM | PMC10940854 |
MV4;11 cells | 18 nM | To evaluate the inhibitory effect of PLX3397 on FLT3-ITD signaling | PMC4522415 | |
RS4;11 cells | 1.8 μM | To evaluate the inhibitory effect of PLX3397 on native FLT3 signaling | PMC4522415 | |
MV4-11 | 0.556 nM | 48 h | To determine the anti-proliferative activity of sitravatinib on MV4-11 cells, the results showed that sitravatinib significantly inhibited MV4-11 cells with an IC50 value of 0.556 nM | PMC9872318 |
MOLM13 | 1.511 nM | 48 h | To determine the anti-proliferative activity of sitravatinib on MOLM13 cells, the results showed that sitravatinib significantly inhibited MOLM13 cells with an IC50 value of 1.511 nM | PMC9872318 |
MOLM-13 | 3 nM | 48 h | To investigate the effect of quizartinib on apoptosis in FLT3-ITD AML cells, results showed that hBMSC-CM significantly reduced quizartinib-induced apoptosis. | PMC9645811 |
MV4-11 | 3 nM | 48 h | To investigate the effect of quizartinib on apoptosis in FLT3-ITD AML cells, results showed that hBMSC-CM significantly reduced quizartinib-induced apoptosis. | PMC9645811 |
In Vivo:
Administration | Dosage | Frequency | Description | References |
Mice | FLT3-ITD+ acute myeloid leukemia model | Oral | 2.5 mg/kg or 5 mg/kg | Once daily for 21 days | To evaluate the impact of quizartinib combined with venetoclax on survival and tumor burden in FLT3-ITD+ leukemic mice. Results showed that the combination significantly prolonged survival and reduced tumor burden compared to monotherapy. | PMC8017817 |
Mice | FLT3(ITD); Tet2−/− AML-like leukemia model | Not specified | 1 mg/kg | 7 consecutive days | To test the anti-leukemia effect of Quizartinib in the FLT3(ITD); Tet2?/? AML-like leukemia model, results showed that Quizartinib significantly reduced the number of leukemia cells. | PMC7578922 |
mice | Flt3ITD;Tet2−/−, Flt3ITD;Dnmt3a−/− and Flt3ITD;Tet2−/−;Dnmt3a−/− leukemia models | intravenous injection | 1 mg/kg | 14 consecutive days | To evaluate the therapeutic effect of Quizartinib and Talazoparib on Flt3ITD;Tet2?/?, Flt3ITD;Dnmt3a?/? and Flt3ITD;Tet2?/?;Dnmt3a?/? leukemia models, results showed that Talazoparib alone or in combination with Quizartinib significantly inhibited Flt3ITD;Tet2?/? and Flt3ITD;Tet2?/?;Dnmt3a?/? leukemia, but was ineffective against Flt3ITD;Dnmt3a?/? leukemia. | PMC8487956 |
Mice | CMML-like disease model | Oral | 10 mg/kg | Once daily for 6 weeks | The JAK inhibitor ruxolitinib significantly reduced the development of CMML-like disease, while the FLT3 inhibitor quizartinib was less effective. | PMC5495118 |
Mice | FLT3-ITD AML mouse model | Oral | 10 mg/kg | Daily administration for 2 weeks | To evaluate the antileukemia activity of Quizartinib in the FLT3-ITD AML mouse model, results showed that Quizartinib significantly reduced leukemia cells in the bone marrow and spleen, and prolonged the survival of mice | PMC10940854 |
Mice | MV4;11 xenograft model | Oral | 10 mg/kg and 30 mg/kg | Daily administration for 21 days | To evaluate the inhibitory effect of PLX3397 on FLT3-ITD-driven MV4;11 xenograft tumors | PMC4522415 |
Mice | MOLM13 xenograft model | Oral | 10 mg/kg | Once daily for 14 days | To evaluate the anti-tumor efficacy of quizartinib in the MOLM13 xenograft model, the results showed that quizartinib significantly prolonged the survival of mice | PMC9872318 |
Mice | NRG-S mouse model | Oral | 2.5 mg/kg | Once daily for 5 days or 84 days | To investigate the effect of quizartinib alone or in combination with everolimus on leukemia burden in FLT3-ITD AML mouse models, results showed that the combination therapy significantly reduced leukemia burden in the bone marrow and prevented relapse. | PMC9645811 |
Clinical Trial:
NCT Number | Conditions | Phases | Recruitment | Completion Date | Locations |
NCT01390337 | Leukemia, Myeloid, Acute | Phase 1 | Completed | - | United States, Florida ... More >> Mayo Clinic Jacksonville Jacksonville, Florida, United States, 32224 United States, Illinois Northwestern University Chicago, Illinois, United States, 60611 United States, Maryland Johns Hopkins Medical Institute Baltimore, Maryland, United States, 21231 United States, New York Memorial-Sloan Kettering Cancer Center New York, New York, United States, 10065 United States, Texas M.D. Anderson Cancer Center Houston, Texas, United States, 77030 Less << |
NCT02428543 | Acute Myeloid Lukemia | Phase 1 Phase 2 | Recruiting | September 2020 | France ... More >> Dr Abdelaziz CHAIB Recruiting Aix-en-Provence, France, 13600 Contact: Abdelaziz CHAIB achaib@ch-aix.fr Principal Investigator: Abdelaziz CHAIB Chu Amiens Recruiting Amiens, France, 80054 Contact: MAROLLEAU Jean Pierre Principal Investigator: MAROLLEAU Jean Pierre CHU d'Angers Recruiting Angers, France, 49033 Contact: Martine GARDEMBAS Magardembas@chu-angers.fr Principal Investigator: Martine GARDEMBAS Hôpital VICTOR DUPOUY Recruiting Argenteuil, France, 95107 Contact: AL JIJAKLI Ahmad ahmad.aljijakli@ch-argenteuil.fr Principal Investigator: AL JIJAKLI Ahmad Dr Edouard RANDIAMALALA Recruiting Bayonne, France, 64100 Contact: Edouard RANDIAMALALA erandiamalala@ch-cotebasque.fr Principal Investigator: Edouard RANDIAMALALA CHU de Besançon Recruiting Besançon, France, 25030 Contact: Fabrice LAROSA flarosa@chu-besançon.fr Principal Investigator: Fabrice LAROSA Dr Thorsten BRAUN Recruiting Bobigny, France, 93000 Contact: Thorsten BRAUN thorsten.braun@aphp.fr Principal Investigator: Thorsten BRAUN CHU Boulogne Sur Mer Recruiting Boulogne Sur Mer cedex, France, 62321 Contact: CHOUFI Bachra b.choufi@ch-boulogne.fr Principal Investigator: CHOUFI Bachra Chr Clemenceau Recruiting Caen Cedex, France, 14033 Contact: REMAN Oumédaly reman-o@chu-caen.fr Principal Investigator: REMAN Oumédaly Hôpital d'Instruction des Armées PERCY Recruiting Clamart, France, 92141 Contact: Jean Valère MALFUSSON jvmalf@free.fr Principal Investigator: Jean Valère MALFUSSON Dr Stéphanie HAÏAT Recruiting Corbeil-essonnes, France, 91100 Contact: Stéphanie HAÏAT Principal Investigator: Stéphanie HAÏAT Hôpital Henri Mondor Recruiting Créteil, France, 94010 Contact: PAUTAS Cécile cecile.pautas@hmn.aphp.fr Principal Investigator: PAUTAS Cécile CHU de Dijon Not yet recruiting Dijon, France, 21079 Contact: CAILLOT Denis denis.caillot@chu-dijon.fr Principal Investigator: CAILLOT Denis Centre hospitalier de Versailles Recruiting Le Chesnay cedex, France, 78157 Contact: Rousselot Philippe 003339638622 phrousselot@ch-versailles.fr Principal Investigator: Rousselot Philippe Hôpital Claude Huriez Recruiting Lille cedex, France, 59037 Contact: QUESNEL Bruno bquesnel@chru-lille.fr Principal Investigator: QUESNEL Bruno CHRU Dupuytren Not yet recruiting Limoges cedex, France, 87042 Contact: TURLURE Pascal pascal.turlure@chu-limoges.fr Principal Investigator: TURLURE Pascal Hôpital Edouard Herriot Recruiting Lyon cedex 03, France, 69437 Contact: THOMAS Xavier xavier.thomas@chu-lyon.fr Principal Investigator: THOMAS Xavier Dr Regis COSTELLO Recruiting Marseille, France, 13000 Contact: Regis COSTELLO regis.costello@ap-hm.fr Principal Investigator: Regis COSTELLO Centre Hospitalier de Meaux Recruiting Meaux, France, 77104 Contact: FRAYFER Jamilé j-frayfer@ch-meaux.fr Principal Investigator: FRAYFER Jamilé Dr Mario OJEDA-URIBE Recruiting Mulhouse, France, 68000 Contact: Mario OJEDA-URIBE ojedam@ch-mulhouse.fr Principal Investigator: Mario OJEDA-URIBE Dr Jacques DELAUNAY Recruiting Nantes, France, 44000 Contact: Jacques DELAUNAY jacques.delaunay@chu-nantes.fr Principal Investigator: Jacques DELAUNAY CHU Nice, Hôpital Archet 1 Recruiting Nice cedex 3, France, 06202 Contact: MANNONE Lionel mannone.l@chu-nice.fr Principal Investigator: MANNONE Lionel CHU de Nîmes Recruiting Nîmes, France, 30029 Contact: Eric JOURDAN eric.jourdan@chu-nimes.fr Principal Investigator: Eric Jourdan Hôpital Saint Antoine Recruiting Paris cedex 12, France, 75751 Contact: ISNARD Françoise francoise.isnard@sat.aphp.fr Principal Investigator: ISNARD Françoise Hôpital Necker Enfants Malades Recruiting Paris cedex 15, France, 75743 Contact: SUAREZ Felipe felipe.suarez@nck.aphp.fr Principal Investigator: SUAREZ Felipe Hôpital Saint Louis Recruiting Paris, France, 75010 Contact: RAFFOUX Emmanuel emmanuel.raffoux@sls.ap-hop-paris.fr Principal Investigator: RAFFOUX Emmanuel Hôpital La Pitié Salpêtrière Recruiting Paris, France, 75013 Contact: UZUNOV Madalina madalina.uzunov@psl.aphp.fr Principal Investigator: UZUNOV Madalina Dr Laurence SANHES Suspended Perpignan, France, 66000 Dr Arnaud PIGNEUX Recruiting Pessac, France, 33604 Contact: Arnaud PIGNEUX arnaud.pigneux@chu-bordeaux.fr Principal Investigator: Arnaud PIGNEUX Centre Hospitalier René Dubos Recruiting Pontoise Cedex, France, 95303 Contact: VAIDA Iona Dana ioana.vaida@ch-pontoise.fr Principal Investigator: VAIDA Iona Dana Marc BERNARD Recruiting Rennes, France, 35000 Contact: Marc BERNARD marc.bernard@chu-rennes.fr Principal Investigator: Marc BERNARD Dr Emilie LEMASLE Recruiting Rouen, France, 76000 Contact: Emilie LEMASLE emilie.lemasle@chb.unicancer.fr Principal Investigator: Emilie LEMASLE Centre Hospitalier René Huguenin Suspended Saint Cloud, France, 92210 Institut de Cancérologie de la Loire Recruiting Saint-Priest-en-Jarez, France, 42270 Contact: Emmanuelle TAVERNIER-TARDY emmanuelle.tavernier@icloire.fr Principal Investigator: Emmanuelle TAVERNIER-TARDY Dr Réda GARIDI Recruiting Saint-Quentin, France, 02100 Contact: Réda GARIDI Principal Investigator: Réda GARIDI Dr Christian RECHER Recruiting Toulouse, France, 31000 Contact: Christian RECHER Principal Investigator: Christian RECHER Centre Hospitalier de Valenciennes Recruiting Valenciennes, France, 59322 Contact: FERNANDES José fernandes-j@ch-valenciennes.fr Principal Investigator: FERNANDES José Less << |
NCT00462761 | Acute Myeloid Leukemia|Leukemi... More >>a|Myelodysplastic Syndrome|AML|MDS Less << | PHASE1 | COMPLETED | 2025-12-09 | University of Alabama at Birmi... More >>ngham, Birmingham, Alabama, 35294, United States|University of Nebraska Medical Center, Omaha, Nebraska, 68198, United States|MD Anderson Cancer Center, Houston, Texas, 77030, United States|Chemotherapy and Immunotherapy Clinic, T'Bilisi, Georgia|Hematology and Chemotherapy Clinic, T'bilisi, Georgia Less << |
NCT02829840 | Leukemia FLT3... More >>-Mutated Acute Myeloid Leukemia FLT3-Mutated High-Risk Myelodysplastic Syndrome Less << | Phase 1 Phase 2 | Withdrawn | - | - |
NCT01468467 | Leukemia, Myeloid, Acute | PHASE1 | COMPLETED | 2025-03-15 | City of Hope, Duarte, Californ... More >>ia, 91010, United States|Northwestern University, Chicago, Illinois, 60611, United States|University of Minnesota, Minneapolis, Minnesota, 55455, United States|M.D. Anderson Cancer Center, Houston, Texas, 77030, United States|Seattle Cancer Care Alliance, Seattle, Washington, 98109, United States Less << |
NCT01576185 | - | Completed | - | United States, California ... More >> Children's Oncology Group Monrovia, California, United States, 91006-3776 Less << | |
NCT02675478 | Relapsed AML|Refractory AML | PHASE1 | COMPLETED | 2018-11-13 | Tokyo, Japan |
NCT02668653 | Acute Myeloid Leukemia ... More >> Leukemia Less << | Phase 3 | Recruiting | November 2020 | - |
NCT02039726 | AML | Phase 3 | Active, not recruiting | July 2019 | - |
NCT01892371 | FLT3 Gene Mutation ... More >> Recurrent Acute Myeloid Leukemia Recurrent Chronic Myelomonocytic Leukemia Recurrent Myelodysplastic Syndrome Refractory Acute Myeloid Leukemia Refractory Chronic Myelomonocytic Leukemia Refractory Myelodysplastic Syndrome Less << | Phase 1 Phase 2 | Recruiting | November 30, 2019 | United States, Texas ... More >> M D Anderson Cancer Center Recruiting Houston, Texas, United States, 77030 Contact: Jorge E. Cortes 713-794-5783 Principal Investigator: Jorge E. Cortes Less << |
NCT03552029 | Acute Myeloid Leukemia | Phase 1 | Recruiting | October 15, 2021 | United States, Texas ... More >> MD Anderson Cancer Center Recruiting Houston, Texas, United States, 77030 Contact: Principal Investigator 713-794-4392 NDaver@mdanderson.org Less << |
NCT02834390 | Acute Myeloid Leukemia | Phase 1 | Completed | - | Japan ... More >> Tokyo, Japan Less << |
NCT02984995 | Leukemia, Myeloid, Acute | PHASE2 | COMPLETED | 2018-09-14 | Aichi, Japan|Akita, Japan|Chib... More >>a, Japan|Fukui, Japan|Fukuoka, Japan|Fukushima, Japan|Gifu, Japan|Gunma, Japan|Hiroshima, Japan|Hokkaido, Japan|Ibaraki, Japan|Kagoshima, Japan|Kanagawa, Japan|Kyoto, Japan|Miyagi, Japan|Nagasaki, Japan|Nara, Japan|Okayama, Japan|Osaka, Japan|Saga, Japan|Saitama, Japan|Shizuoka, Japan|Tochigi, Japan|Tokyo, Japan|Toyama, Japan|Yamagata, Japan|Yamanashi, Japan Less << |
NCT03735875 | Acute Myeloid Leukemia With FL... More >>T3/ITD Mutation FLT3 Gene Mutation FLT3 Internal Tandem Duplication Recurrent Acute Myeloid Leukemia Refractory Acute Leukemia Less << | Phase 1 Phase 2 | Not yet recruiting | December 31, 2019 | United States, Texas ... More >> M D Anderson Cancer Center Not yet recruiting Houston, Texas, United States, 77030 Contact: Naval G. Daver 713-794-4392 Principal Investigator: Naval G. Daver Less << |
NCT01565668 | Leukemia, Myeloid, Acute | PHASE2 | COMPLETED | 2025-03-15 | UCLA School of Medicine, Los A... More >>ngeles, California, 90095, United States|Northwestern University, Chicago, Illinois, 60611, United States|University of Chicago, Chicago, Illinois, 60637, United States|University of Maryland Greenebaum Cancer Center, Baltimore, Maryland, 21201, United States|John Hopkins University, Baltimore, Maryland, 21231, United States|Tufts University School of Medicine-Tufts Medical Center, Boston, Massachusetts, 02111, United States|University of Minnesota, Minneapolis, Minnesota, 55455, United States|Mayo Clinic, Rochester, Minnesota, 55905, United States|Hackensack University Medical Center, Hackensack, New Jersey, 07601, United States|Memorial Sloan-Kettering Cancer Center, New York, New York, 10021, United States|Weill Cornell Medical College, New York, New York, 10065, United States|Penn State Milton S. Hershey Medical Center, Hershey, Pennsylvania, 17033, United States|Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, 19104, United States|Medical University of South Carolina, Hollings Cancer Center, Charleston, South Carolina, 29403, United States|Vanderbilt University, Vanderbilt Ingram Cancer Center, Nashville, Tennessee, 37232, United States|UT Southwestern Medical Center, Simmons Cancer Center, Dallas, Texas, 75390, United States|MD Anderson, Houston, Texas, 77030, United States|Fred Hutchinson Cancer Research Center, Seattle, Washington, 98109, United States|CHU d'Angers, Angers, 49033, France|CHU de Grenoble, Grenoble, 38043, France|H?pital Saint Antoine, Paris, 75571, France|H?pital Haut Lévêque, Pessac, 33600, France|Universitaria Policlinico S. Orsola Malpighi, Institute of Hemtology "L. & A. Seragnoli", Bologna, 40138, Italy|Nottingham University Hospitals, Nottingham, England, United Kingdom Less << |
NCT03723681 | Acute Myeloid Leukemia (AML) | PHASE1 | COMPLETED | 2022-03-03 | Institute of Hematology and Bl... More >>ood Diseases Hospital Chinese Academy of Medical Sciences, Tianjin, 300020, China Less << |
NCT03135054 | AML FLT3-ITD ... More >>Mutation Less << | Phase 2 | Recruiting | October 1, 2021 | Hong Kong ... More >> The University of Hong Kong Recruiting Hong Kong, Hong Kong Contact: Chunxiao Zhang, SC 852-22554361 chunxiao@hku.hk Less << |
NCT03661307 | Acute Myeloid Leukemia With FL... More >>T3/ITD Mutation Blasts More Than 10 Percent of Bone Marrow Nucleated Cells Blasts More Than 10 Percent of Peripheral Blood White Cells Myelodysplastic Syndrome Recurrent Acute Myeloid Leukemia Recurrent Myelodysplastic Syndrome Less << | Phase 1 Phase 2 | Recruiting | January 1, 2020 | United States, Texas ... More >> M D Anderson Cancer Center Recruiting Houston, Texas, United States, 77030 Contact: Musa Yilmaz 713-745-9945 Principal Investigator: Musa Yilmaz Less << |
NCT03746912 | - | - | - | - | |
NCT06740799 | Hepatic Impairment | PHASE1 | RECRUITING | 2025-06-30 | Clinical Pharmacology of Miami... More >>, LLC, Miami, Florida, 33014, United States|Advanced Pharma, Miami, Florida, 33147, United States|GCP Research, Saint Petersburg, Florida, 33705, United States Less << |
NCT04473664 | Hepatic Impairment|Moderate Im... More >>paired Hepatic Function Less << | PHASE1 | COMPLETED | 2021-07-22 | Clinical Pharmacology of Miami... More >>, LLC, Miami, Florida, 33014-3616, United States|Advanced Pharma, Miami, Florida, 33147, United States|Orlando Clinical Research Center, Orlando, Florida, 32809, United States Less << |
Bio Calculators | ||||
Preparing Stock Solutions | ![]() |
1mg | 5mg | 10mg |
1 mM 5 mM 10 mM |
1.78mL 0.36mL 0.18mL |
8.92mL 1.78mL 0.89mL |
17.84mL 3.57mL 1.78mL |