DGIdb - QUIZARTINIB Drug Record

QUIZARTINIB chembl:CHEMBL576982 Antineoplastic

Alternate Names:

AC010220
QUIZARTINIB
AC220
ASP-2689
AC-010220
AC-220
AC 220
N-(5-(1,1-DIMETHYLETHYL)ISOXAZOL-3-YL)-N'-(4-(7-(2-(MORPHOLIN-4-YL)ETHOXY)IMIDAZO(2,1-B)BENZOTHIAZOL-2-YL)PHENYL)UREA
AC 010220
chemidplus:950769-58-1
drugbank:12874
pubchem.compound:24889392
chembl:CHEMBL576982

Drug Info:

FDA Approval	not approved
Drug Class	Small molecule
Drug Indications	antineoplastic agent
Drug Class	Kinase Inhibitors

(6 More Sources)

Publications:

Kancha et al., 2007, Sensitivity toward sorafenib and sunitinib varies between different activating and drug-resistant FLT3-ITD mutations., Exp. Hematol.
Mardis et al., 2009, Recurring mutations found by sequencing an acute myeloid leukemia genome., N. Engl. J. Med.
Knapper et al., 2006, A phase 2 trial of the FLT3 inhibitor lestaurtinib (CEP701) as first-line treatment for older patients with acute myeloid leukemia not considered fit for intensive chemotherapy., Blood
Piloto et al., 2007, Prolonged exposure to FLT3 inhibitors leads to resistance via activation of parallel signaling pathways., Blood
Smith et al., 2013, Activity of ponatinib against clinically-relevant AC220-resistant kinase domain mutants of FLT3-ITD., Blood
Zimmerman et al., 2013, Crenolanib is active against models of drug-resistant FLT3-ITD-positive acute myeloid leukemia., Blood
Clark et al., 2004, Variable sensitivity of FLT3 activation loop mutations to the small molecule tyrosine kinase inhibitor MLN518., Blood
Allen et al., 2013, The importance of relative mutant level for evaluating impact on outcome of KIT, FLT3 and CBL mutations in core-binding factor acute myeloid leukemia., Leukemia
Cortes et al., 2013, 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.
Martelli et al., 2013, Mutational landscape of AML with normal cytogenetics: biological and clinical implications., Blood Rev.
Uras et al., 2016, Palbociclib treatment of FLT3-ITD+ AML cells uncovers a kinase-dependent transcriptional regulation of FLT3 and PIM1 by CDK6., Blood
Cooper et al., 2016, A Phase I Study of Quizartinib Combined with Chemotherapy in Relapsed Childhood Leukemia: A Therapeutic Advances in Childhood Leukemia & Lymphoma (TACL) Study., Clin. Cancer Res.
Albers et al., 2013, The secondary FLT3-ITD F691L mutation induces resistance to AC220 in FLT3-ITD+ AML but retains in vitro sensitivity to PKC412 and Sunitinib., Leukemia
Yamamoto et al., 2001, Activating mutation of D835 within the activation loop of FLT3 in human hematologic malignancies., Blood
Smith et al., 2012, Validation of ITD mutations in FLT3 as a therapeutic target in human acute myeloid leukaemia., Nature
Wang et al., 2012, MicroRNAs in liver disease., Gastroenterology
Zhang et al., 2014, Reversal of acquired drug resistance in FLT3-mutated acute myeloid leukemia cells via distinct drug combination strategies., Clin. Cancer Res.
Smith et al., 2013, The role of kinase inhibitors in the treatment of patients with acute myeloid leukemia., Am Soc Clin Oncol Educ Book
Man et al., 2012, Sorafenib treatment of FLT3-ITD(+) acute myeloid leukemia: favorable initial outcome and mechanisms of subsequent nonresponsiveness associated with the emergence of a D835 mutation., Blood
Fischer et al., 2010, Phase IIB trial of oral Midostaurin (PKC412), the FMS-like tyrosine kinase 3 receptor (FLT3) and multi-targeted kinase inhibitor, in patients with acute myeloid leukemia and high-risk myelodysplastic syndrome with either wild-type or mutated FLT3., J. Clin. Oncol.
MacConaill et al., 2014, Prospective enterprise-level molecular genotyping of a cohort of cancer patients., J Mol Diagn
Opatz et al., 2013, Exome sequencing identifies recurring FLT3 N676K mutations in core-binding factor leukemia., Blood
Bagrintseva et al., 2004, Mutations in the tyrosine kinase domain of FLT3 define a new molecular mechanism of acquired drug resistance to PTK inhibitors in FLT3-ITD-transformed hematopoietic cells., Blood
Mathews et al., 2007, Impact of FLT3 mutations and secondary cytogenetic changes on the outcome of patients with newly diagnosed acute promyelocytic leukemia treated with a single agent arsenic trioxide regimen., Haematologica
Eisenhoffer et al., 2012, Crowding induces live cell extrusion to maintain homeostatic cell numbers in epithelia., Nature
Jourdan et al., 2013, Prospective evaluation of gene mutations and minimal residual disease in patients with core binding factor acute myeloid leukemia., Blood
Williams AB et al., 2013, Mutations of FLT3/ITD confer resistance to multiple tyrosine kinase inhibitors., Leukemia
Brown et al., 2005, FLT3 inhibition selectively kills childhood acute lymphoblastic leukemia cells with high levels of FLT3 expression., Blood
Tornillo et al., 2006, An update on molecular genetics of gastrointestinal stromal tumours., J. Clin. Pathol.
Cairoli et al., 2006, Prognostic impact of c-KIT mutations in core binding factor leukemias: an Italian retrospective study., Blood
Nakagomi et al., 2007, Juxtamembrane-type c-kit gene mutation found in aggressive systemic mastocytosis induces imatinib-resistant constitutive KIT activation., Lab. Invest.
Gleixner et al., 2007, Synergistic growth-inhibitory effects of two tyrosine kinase inhibitors, dasatinib and PKC412, on neoplastic mast cells expressing the D816V-mutated oncogenic variant of KIT., Haematologica
Pan et al., 2007, EXEL-0862, a novel tyrosine kinase inhibitor, induces apoptosis in vitro and ex vivo in human mast cells expressing the KIT D816V mutation., Blood
Todd et al., 2013, Secondary c-Kit mutations confer acquired resistance to RTK inhibitors in c-Kit mutant melanoma cells., Pigment Cell Melanoma Res
Gotlib et al., 2005, Activity of the tyrosine kinase inhibitor PKC412 in a patient with mast cell leukemia with the D816V KIT mutation., Blood
Ustun et al., 2009, Chemotherapy and dasatinib induce long-term hematologic and molecular remission in systemic mastocytosis with acute myeloid leukemia with KIT D816V., Leuk. Res.
Wasag et al., 2011, Novel, activating KIT-N822I mutation in familial cutaneous mastocytosis., Exp. Hematol.
Gajiwala et al., 2009, KIT kinase mutants show unique mechanisms of drug resistance to imatinib and sunitinib in gastrointestinal stromal tumor patients., Proc. Natl. Acad. Sci. U.S.A.
Johnson et al., 2013, Hidden mastocytosis in acute myeloid leukemia with t(8;21)(q22;q22)., Am. J. Clin. Pathol.
Kampa-Schittenhelm et al., 2013, 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
Taylor et al., 2012, Flt3 inhibitor AC220 is a potent therapy in a mouse model of myeloproliferative disease driven by enhanced wild-type Flt3 signaling., Blood
Traer et al., 2016, FGF2 from Marrow Microenvironment Promotes Resistance to FLT3 Inhibitors in Acute Myeloid Leukemia., Cancer Res.

QUIZARTINIB FLT3

Interaction Score: 2.99

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Trial Name AC-220

Novel drug target Established target

Indication/Tumor Type Advanced Solid Tumor

PMIDs:
17889720 19657110 16857985 17047150 23430109 24046014 15256420 23783394 24002496 23261068 27099147 26920889 23392356 11290608 22504184 22504185 24619500 23714533 22368270 20733134 25157968 23878140 14604974 17606455 22504183 23321257 22858906 15374878

Sources:
TTD TdgClinicalTrial JAX-CKB MyCancerGenome DoCM ChemblInteractions OncoKB COSMIC CIViC
QUIZARTINIB CBL

Interaction Score: 2.29

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type bone marrow cancer

Response Type sensitive

Approval Status Preclinical

PMIDs:
22990016

Sources:
JAX-CKB
QUIZARTINIB KIT

Interaction Score: 2.03

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Pathway activation

Clinical Status preclinical

Variant Effect gain-of-function

PMIDs:
16731599 16384925 17259998 18024392 16912224 23582185 15972446 23714533 18986703 21689725 19164557 22504184 25157968 24045550 23497317

Sources:
JAX-CKB ChemblInteractions DoCM
QUIZARTINIB IDH2

Interaction Score: 1.14

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Enasidenib + Quizartinib

Indication/Tumor Type acute myeloid leukemia

Response Type predicted – sensitive

PMIDs:
None found

Sources:
JAX-CKB
QUIZARTINIB FGF2

Interaction Score: 0.65

Interaction Types & Directionality:

n/a

Interaction Info:

PMIDs:
27671675

Sources:
CIViC
QUIZARTINIB CSF1R

Interaction Score: 0.14

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Mechanism of Interaction Macrophage colony stimulating factor receptor inhibitor

Direct Interaction yes

PMIDs:
None found

Sources:
ChemblInteractions
QUIZARTINIB RET

Interaction Score: 0.11

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Mechanism of Interaction Tyrosine-protein kinase receptor RET inhibitor

Direct Interaction yes

PMIDs:
None found

Sources:
ChemblInteractions
QUIZARTINIB PDGFRA

Interaction Score: 0.11

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Mechanism of Interaction Platelet-derived growth factor receptor inhibitor

Direct Interaction yes

PMIDs:
None found

Sources:
ChemblInteractions
QUIZARTINIB PDGFRB

Interaction Score: 0.1

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Mechanism of Interaction Platelet-derived growth factor receptor inhibitor

Direct Interaction yes

PMIDs:
None found

Sources:
ChemblInteractions

MyCancerGenome: QUIZARTINIB
- Version: 20-Jun-2017
Alternate Names:

AC220 Development Name

QUIZARTINIB Generic Name

Drug Info:

Drug Class Kinase Inhibitors

Publications:
TdgClinicalTrial: QUIZARTINIB
- Version: January-2014
Alternate Names:

Drug Info:

Drug Indications antineoplastic agent

Drug Class Small molecule

FDA Approval not approved

Publications:

JAX-CKB: Quizartinib

Version: 27-September-2017

Alternate Names:

Drug Info:

Publications:

Cortes et al., 2013, 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.

Uras et al., 2016, Palbociclib treatment of FLT3-ITD+ AML cells uncovers a kinase-dependent transcriptional regulation of FLT3 and PIM1 by CDK6., Blood

Cooper et al., 2016, A Phase I Study of Quizartinib Combined with Chemotherapy in Relapsed Childhood Leukemia: A Therapeutic Advances in Childhood Leukemia & Lymphoma (TACL) Study., Clin. Cancer Res.

DoCM: QUIZARTINIB

Version: 27-September-2017

Alternate Names:

Drug Info:

Publications:

Wasag et al., 2011, Novel, activating KIT-N822I mutation in familial cutaneous mastocytosis., Exp. Hematol.

Johnson et al., 2013, Hidden mastocytosis in acute myeloid leukemia with t(8;21)(q22;q22)., Am. J. Clin. Pathol.

Gajiwala et al., 2009, KIT kinase mutants show unique mechanisms of drug resistance to imatinib and sunitinib in gastrointestinal stromal tumor patients., Proc. Natl. Acad. Sci. U.S.A.

CIViC: QUIZARTINIB

Version: 14-September-2020

Alternate Names:

Drug Info:

Publications:

Smith et al., 2013, Activity of ponatinib against clinically-relevant AC220-resistant kinase domain mutants of FLT3-ITD., Blood

Smith et al., 2012, Validation of ITD mutations in FLT3 as a therapeutic target in human acute myeloid leukaemia., Nature

Opatz et al., 2013, Exome sequencing identifies recurring FLT3 N676K mutations in core-binding factor leukemia., Blood

TTD: AC220
- Version: 2020.06.01
Alternate Names:

D07KYT TTD Drug ID

Drug Info:

Publications:
ChemblDrugs: chembl:CHEMBL576982
- Version: ChEMBL_27
Alternate Names:

Drug Info:

Publications:
OncoKB: Quizartinib
- Version: 23-July-2020
Alternate Names:

Drug Info:

Publications:
ChemblInteractions: CHEMBL576982
- Version: chembl_23
Alternate Names:

Drug Info:

Publications:
COSMIC: Quizartinib
- Version: 4-Sep-2020
Alternate Names:

Drug Info:

Publications:

Trial Name	AC-220
Novel drug target	Established target
Indication/Tumor Type	Advanced Solid Tumor

Indication/Tumor Type	bone marrow cancer
Response Type	sensitive
Approval Status	Preclinical

Pathway	activation
Clinical Status	preclinical
Variant Effect	gain-of-function

combination therapy	Enasidenib + Quizartinib
Indication/Tumor Type	acute myeloid leukemia
Response Type	predicted – sensitive

Mechanism of Interaction	Macrophage colony stimulating factor receptor inhibitor
Direct Interaction	yes

Mechanism of Interaction	Tyrosine-protein kinase receptor RET inhibitor
Direct Interaction	yes

Mechanism of Interaction	Platelet-derived growth factor receptor inhibitor
Direct Interaction	yes

QUIZARTINIB Drug Record

QUIZARTINIB chembl:CHEMBL576982 Antineoplastic

Alternate Names:

Drug Info:

Publications:

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info: Trial Name AC-220 Novel drug target Established target Indication/Tumor Type Advanced Solid Tumor

PMIDs: 17889720 19657110 16857985 17047150 23430109 24046014 15256420 23783394 24002496 23261068 27099147 26920889 23392356 11290608 22504184 22504185 24619500 23714533 22368270 20733134 25157968 23878140 14604974 17606455 22504183 23321257 22858906 15374878

Sources: TTD TdgClinicalTrial JAX-CKB MyCancerGenome DoCM ChemblInteractions OncoKB COSMIC CIViC

Interaction Types & Directionality: n/a

Interaction Info: Indication/Tumor Type bone marrow cancer Response Type sensitive Approval Status Preclinical

PMIDs: 22990016

Sources: JAX-CKB

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info: Pathway activation Clinical Status preclinical Variant Effect gain-of-function

PMIDs: 16731599 16384925 17259998 18024392 16912224 23582185 15972446 23714533 18986703 21689725 19164557 22504184 25157968 24045550 23497317

Sources: JAX-CKB ChemblInteractions DoCM

Interaction Types & Directionality: n/a

Interaction Info: combination therapy Enasidenib + Quizartinib Indication/Tumor Type acute myeloid leukemia Response Type predicted – sensitive

PMIDs: None found

Sources: JAX-CKB

Interaction Types & Directionality: n/a

Interaction Info:

PMIDs: 27671675

Sources: CIViC

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info: Mechanism of Interaction Macrophage colony stimulating factor receptor inhibitor Direct Interaction yes

PMIDs: None found

Sources: ChemblInteractions

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info: Mechanism of Interaction Tyrosine-protein kinase receptor RET inhibitor Direct Interaction yes

PMIDs: None found

Sources: ChemblInteractions

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info: Mechanism of Interaction Platelet-derived growth factor receptor inhibitor Direct Interaction yes

PMIDs: None found

Sources: ChemblInteractions

Interaction Types & Directionality: inhibitor (inhibitory)

Interaction Info: Mechanism of Interaction Platelet-derived growth factor receptor inhibitor Direct Interaction yes

PMIDs: None found

Sources: ChemblInteractions

MyCancerGenome: QUIZARTINIB

Alternate Names: AC220 Development Name QUIZARTINIB Generic Name

Drug Info: Drug Class Kinase Inhibitors

Publications:

TdgClinicalTrial: QUIZARTINIB

Alternate Names:

Drug Info: Drug Indications antineoplastic agent Drug Class Small molecule FDA Approval not approved

Publications:

JAX-CKB: Quizartinib

Alternate Names:

Drug Info:

DoCM: QUIZARTINIB

Alternate Names:

Drug Info:

CIViC: QUIZARTINIB

Alternate Names:

Drug Info:

TTD: AC220

Alternate Names: D07KYT TTD Drug ID

Drug Info:

Publications:

ChemblDrugs: chembl:CHEMBL576982

Alternate Names:

Drug Info:

Publications:

OncoKB: Quizartinib

Alternate Names:

Drug Info:

Publications:

ChemblInteractions: CHEMBL576982

Alternate Names:

Drug Info:

Publications:

COSMIC: Quizartinib

Alternate Names:

Drug Info:

Publications:

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Trial Name AC-220

Novel drug target Established target

Indication/Tumor Type Advanced Solid Tumor

PMIDs:
17889720 19657110 16857985 17047150 23430109 24046014 15256420 23783394 24002496 23261068 27099147 26920889 23392356 11290608 22504184 22504185 24619500 23714533 22368270 20733134 25157968 23878140 14604974 17606455 22504183 23321257 22858906 15374878

Sources:
TTD TdgClinicalTrial JAX-CKB MyCancerGenome DoCM ChemblInteractions OncoKB COSMIC CIViC

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type bone marrow cancer

Response Type sensitive

Approval Status Preclinical

PMIDs:
22990016

Sources:
JAX-CKB

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Pathway activation

Clinical Status preclinical

Variant Effect gain-of-function

PMIDs:
16731599 16384925 17259998 18024392 16912224 23582185 15972446 23714533 18986703 21689725 19164557 22504184 25157968 24045550 23497317

Sources:
JAX-CKB ChemblInteractions DoCM

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Enasidenib + Quizartinib

Indication/Tumor Type acute myeloid leukemia

Response Type predicted – sensitive

PMIDs:
None found

Sources:
JAX-CKB

Interaction Types & Directionality:

n/a

PMIDs:
27671675

Sources:
CIViC

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Mechanism of Interaction Macrophage colony stimulating factor receptor inhibitor

Direct Interaction yes

PMIDs:
None found

Sources:
ChemblInteractions

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Mechanism of Interaction Tyrosine-protein kinase receptor RET inhibitor

Direct Interaction yes

PMIDs:
None found

Sources:
ChemblInteractions

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Mechanism of Interaction Platelet-derived growth factor receptor inhibitor

Direct Interaction yes

PMIDs:
None found

Sources:
ChemblInteractions

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Mechanism of Interaction Platelet-derived growth factor receptor inhibitor

Direct Interaction yes

PMIDs:
None found

Sources:
ChemblInteractions

Alternate Names:

AC220 Development Name

QUIZARTINIB Generic Name

Drug Info:

Drug Class Kinase Inhibitors

Drug Info:

Drug Indications antineoplastic agent

Drug Class Small molecule

FDA Approval not approved

Alternate Names:

D07KYT TTD Drug ID