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Ref Type Journal Article
PMID (35395091)
Authors Ferng TT, Terada D, Ando M, Tarver TC, Chaudhary F, Lin KC, Logan AC, Smith CC
Title The Irreversible FLT3 Inhibitor FF-10101 Is Active Against a Diversity of FLT3 Inhibitor Resistance Mechanisms.
Journal Molecular cancer therapeutics
Vol 21
Issue 5
Date 2022 May 04
URL
Abstract Text Small-molecule FLT3 inhibitors have recently improved clinical outcomes for patients with FLT3-mutant acute myeloid leukemia (AML) after many years of development, but resistance remains an important clinical problem. FF-10101 is the first irreversible, covalent inhibitor of FLT3 which has previously shown activity against FLT3 tyrosine kinase inhibitor resistance-causing FLT3 F691L and D835 mutations. We report that FF-10101 is also active against an expanded panel of clinically identified FLT3 mutations associated with resistance to other FLT3 inhibitors. We also demonstrate that FF-10101 can potentially address resistance mechanisms associated with growth factors present in the bone marrow microenvironment but is vulnerable to mutation at C695, the amino acid required for covalent FLT3 binding. These data suggest that FF-10101 possesses a favorable resistance profile that may contribute to improved single-agent efficacy when used in patients with FLT3-mutant AML.

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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Drug Name Trade Name Synonyms Drug Classes Drug Description
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
FLT3 G697S missense unknown FLT3 G697S lies within the protein kinase domain of the Flt3 protein (UniProt.org). G697S has been demonstrated to promote secondary drug resistance in the context of FLT3 internal tandem duplication (FLT3-ITD) mutations (PMID: 35395091), but has not been biochemically characterized and therefore, its effect on Flt3 protein function is unknown (PubMed, Nov 2022). Y
FLT3 Y693C missense unknown FLT3 Y693C lies within the protein kinase domain of the Flt3 protein (UniProt.org). Y693C has been demonstrated to promote secondary drug resistance in the context of FLT3 internal tandem duplication (FLT3-ITD) mutations (PMID: 32040554, PMID: 35395091), but has not been biochemically characterized and therefore, its effect on Flt3 protein function is unknown (PubMed, Nov 2022). Y
FLT3 Y693F missense unknown FLT3 Y693F lies within the protein kinase domain of the Flt3 protein (UniProt.org). Y693F has been identified in the scientific literature (PMID: 35395091), but has not been biochemically characterized and therefore, its effect on Flt3 protein function is unknown (PubMed, Nov 2022).
FLT3 Y693N missense unknown FLT3 Y693N lies within the protein kinase domain of the Flt3 protein (UniProt.org). Y693N has been demonstrated to promote secondary drug resistance in the context of FLT3 internal tandem duplication (FLT3-ITD) mutations (PMID: 32040554, PMID: 35395091), but has not been biochemically characterized and therefore, its effect on Flt3 protein function is unknown (PubMed, Nov 2022). Y
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
FLT3 exon 14 ins FLT3 D835N hematologic cancer sensitive Midostaurin Preclinical - Cell culture Actionable In a preclinical study, Rydapt (midostaurin) treatment inhibited growth of transformed hematologic cells expressing FLT3-ITD and FLT3 D835N in culture (PMID: 35395091). 35395091
FLT3 exon 14 ins FLT3 C695S hematologic cancer predicted - resistant FF-10101 Preclinical - Cell culture Actionable In a preclinical study, transformed hematologic cells expressing FLT3-ITD and FLT3 C695S were resistant to treatment with FF-10101 in culture (PMID: 35395091). 35395091
FLT3 exon 14 ins FLT3 K429E hematologic cancer sensitive Midostaurin Preclinical - Cell culture Actionable In a preclinical study, Rydapt (midostaurin) treatment inhibited growth of transformed hematologic cells expressing FLT3-ITD and FLT3 K429E in culture (PMID: 35395091). 35395091
FLT3 exon 14 ins FLT3 D835del hematologic cancer sensitive Crenolanib Preclinical - Cell culture Actionable In a preclinical study, Crenolanib (CP-868596) treatment inhibited growth of transformed hematologic cells expressing FLT3-ITD and FLT3 D835del in culture (PMID: 35395091). 35395091
FLT3 exon 14 ins FLT3 D835G hematologic cancer sensitive Gilteritinib Preclinical - Cell culture Actionable In a preclinical study, Xospata (gilteritinib) treatment inhibited growth of transformed hematologic cells expressing FLT3-ITD and FLT3 D835G in culture (PMID: 35395091). 35395091
FLT3 exon 14 ins FLT3 Y693C hematologic cancer predicted - resistant Crenolanib Preclinical - Cell culture Actionable In a preclinical study, transformed hematologic cells expressing FLT3-ITD and FLT3 Y693C were moderately resistant to Crenolanib (CP-868596) treatment in culture (PMID: 35395091). 35395091
FLT3 exon 14 ins FLT3 C681S hematologic cancer sensitive FF-10101 Preclinical - Cell culture Actionable In a preclinical study, FF-10101 treatment inhibited growth of transformed hematologic cells expressing FLT3-ITD and FLT3 C681S in culture (PMID: 35395091). 35395091
FLT3 exon 14 ins FLT3 D835E hematologic cancer sensitive Midostaurin Preclinical - Cell culture Actionable In a preclinical study, Rydapt (midostaurin) treatment inhibited growth of transformed hematologic cells expressing FLT3-ITD and FLT3 D835E in culture (PMID: 35395091). 35395091
FLT3 exon 14 ins FLT3 K429E hematologic cancer sensitive FF-10101 Preclinical - Cell culture Actionable In a preclinical study, FF-10101 treatment inhibited growth of transformed hematologic cells expressing FLT3-ITD and FLT3 K429E in culture (PMID: 35395091). 35395091
FLT3 exon 14 ins FLT3 D835del hematologic cancer resistant Quizartinib Preclinical - Cell culture Actionable In a preclinical study, transformed hematologic cells expressing FLT3-ITD and FLT3 D835del were resistant to treatment with Vanflyta (quizartinib) in culture (PMID: 35395091). 35395091
FLT3 exon 14 ins FLT3 D835H hematologic cancer sensitive Crenolanib Preclinical - Cell culture Actionable In a preclinical study, Crenolanib (CP-868596) treatment inhibited growth of transformed hematologic cells expressing FLT3-ITD and FLT3 D835H in culture (PMID: 35395091). 35395091
FLT3 exon 14 ins FLT3 D835del hematologic cancer sensitive Midostaurin Preclinical - Cell culture Actionable In a preclinical study, Rydapt (midostaurin) treatment inhibited growth of transformed hematologic cells expressing FLT3-ITD and FLT3 D835del in culture (PMID: 35395091). 35395091
FLT3 exon 14 ins FLT3 D835H hematologic cancer sensitive Gilteritinib Preclinical - Cell culture Actionable In a preclinical study, Xospata (gilteritinib) treatment inhibited growth of transformed hematologic cells expressing FLT3-ITD and FLT3 D835H in culture (PMID: 35395091). 35395091
FLT3 exon 14 ins FLT3 D835E hematologic cancer sensitive Crenolanib Preclinical - Cell culture Actionable In a preclinical study, Crenolanib (CP-868596) treatment inhibited growth of transformed hematologic cells expressing FLT3-ITD and FLT3 D835E in culture (PMID: 35395091). 35395091
FLT3 exon 14 ins FLT3 D835G hematologic cancer sensitive Crenolanib Preclinical - Cell culture Actionable In a preclinical study, Crenolanib (CP-868596) treatment inhibited growth of transformed hematologic cells expressing FLT3-ITD and FLT3 D835G in culture (PMID: 35395091). 35395091
FLT3 exon 14 ins FLT3 Y693N hematologic cancer resistant Gilteritinib Preclinical - Cell culture Actionable In a preclinical study, transformed hematologic cells expressing FLT3-ITD and FLT3 Y693N were moderately resistant to Xospata (gilteritinib) treatment in culture (PMID: 35395091). 35395091
FLT3 exon 14 ins FLT3 N676K hematologic cancer sensitive Quizartinib Preclinical - Cell culture Actionable In a preclinical study, Vanflyta (quizartinib) treatment inhibited growth of transformed hematologic cells expressing FLT3-ITD and FLT3 N676K in culture (PMID: 35395091). 35395091
FLT3 exon 14 ins FLT3 D835E hematologic cancer sensitive Quizartinib Preclinical - Cell culture Actionable In a preclinical study, Vanflyta (quizartinib) treatment inhibited growth of transformed hematologic cells expressing FLT3-ITD and FLT3 D835E in culture (PMID: 35395091). 35395091
FLT3 exon 14 ins FLT3 D835V hematologic cancer sensitive Midostaurin Preclinical - Cell culture Actionable In a preclinical study, Rydapt (midostaurin) treatment inhibited growth of transformed hematologic cells expressing FLT3-ITD and FLT3 D835V in culture (PMID: 35395091). 35395091
FLT3 exon 14 ins FLT3 D835E hematologic cancer sensitive Gilteritinib Preclinical - Cell culture Actionable In a preclinical study, Xospata (gilteritinib) treatment inhibited growth of transformed hematologic cells expressing FLT3-ITD and FLT3 D835E in culture (PMID: 35395091). 35395091
FLT3 exon 14 ins NRAS Q61K acute myeloid leukemia resistant Gilteritinib Preclinical - Cell culture Actionable In a preclinical study, acute myeloid leukemia cells harboring a FLT3-ITD mutation and expressing NRAS Q61K demonstrated resistance to treatment with Xospata (gilteritinib) in culture (PMID: 35395091). 35395091
FLT3 exon 14 ins FLT3 D835F hematologic cancer sensitive FF-10101 Preclinical - Cell culture Actionable In a preclinical study, FF-10101 treatment inhibited growth of transformed hematologic cells expressing FLT3-ITD and FLT3 D835F in culture (PMID: 35395091). 35395091
FLT3 exon 14 ins FLT3 Y693C hematologic cancer predicted - resistant Midostaurin Preclinical - Cell culture Actionable In a preclinical study, transformed hematologic cells expressing FLT3-ITD and FLT3 Y693C were moderately resistant to Rydapt (midostaurin) treatment in culture (PMID: 35395091). 35395091
FLT3 exon 14 ins FLT3 D698N hematologic cancer sensitive FF-10101 Preclinical - Cell culture Actionable In a preclinical study, FF-10101 treatment inhibited growth of transformed hematologic cells expressing FLT3-ITD and FLT3 D698N in culture (PMID: 35395091). 35395091
FLT3 exon 14 ins FLT3 D835N acute myeloid leukemia sensitive FF-10101 Preclinical - Cell culture Actionable In a preclinical study, FF-10101 treatment inhibited growth of acute myeloid leukemia cells harboring FLT3-ITD and FLT3 D835N in culture (PMID: 35395091). 35395091
FLT3 exon 14 ins FLT3 N676K hematologic cancer sensitive FF-10101 Preclinical - Cell culture Actionable In a preclinical study, FF-10101 treatment inhibited growth of transformed hematologic cells expressing FLT3-ITD and FLT3 N676K in culture (PMID: 35395091). 35395091
FLT3 exon 14 ins FLT3 F691L acute myeloid leukemia sensitive FF-10101 Preclinical - Cell culture Actionable In a preclinical study, acute myeloid leukemia cells harboring FLT3-ITD and FLT3 F691L demonstrated sensitivity to treatment with FF-10101 in culture, but were less sensitive compared to cells harboring FLT3-ITD alone (PMID: 35395091). 35395091
FLT3 exon 14 ins FLT3 D835N hematologic cancer sensitive Gilteritinib Preclinical - Cell culture Actionable In a preclinical study, Xospata (gilteritinib) treatment inhibited growth of transformed hematologic cells expressing FLT3-ITD and FLT3 D835N in culture (PMID: 35395091). 35395091
FLT3 exon 14 ins hematologic cancer sensitive Gilteritinib Preclinical - Cell culture Actionable In a preclinical study, Xospata (gilteritinib) treatment inhibited growth of transformed hematologic cells expressing FLT3-ITD in culture (PMID: 35395091). 35395091
FLT3 exon 14 ins FLT3 A848P acute myeloid leukemia predicted - sensitive FF-10101 Preclinical - Cell culture Actionable In a preclinical study, acute myeloid leukemia cells harboring FLT3-ITD and FLT3 A848P demonstrated sensitivity to treatment with FF-10101 in culture (PMID: 35395091). 35395091
FLT3 exon 14 ins FLT3 D835H hematologic cancer sensitive Midostaurin Preclinical - Cell culture Actionable In a preclinical study, Rydapt (midostaurin) treatment inhibited growth of transformed hematologic cells expressing FLT3-ITD and FLT3 D835H in culture (PMID: 35395091). 35395091
FLT3 exon 14 ins FLT3 D835G hematologic cancer sensitive FF-10101 Preclinical - Cell culture Actionable In a preclinical study, FF-10101 treatment inhibited growth of transformed hematologic cells expressing FLT3-ITD and FLT3 D835G in culture (PMID: 35395091). 35395091
FLT3 exon 14 ins NRAS G12C acute myeloid leukemia resistant Gilteritinib Preclinical - Biochemical Actionable In a preclinical study, acute myeloid leukemia cells harboring a FLT3-ITD mutation and expressing NRAS G12C demonstrated resistance to treatment with Xospata (gilteritinib) in culture (PMID: 35395091). 35395091
FLT3 exon 14 ins FLT3 N676K hematologic cancer sensitive Gilteritinib Preclinical - Cell culture Actionable In a preclinical study, Xospata (gilteritinib) treatment inhibited growth of transformed hematologic cells expressing FLT3-ITD and FLT3 N676K in culture (PMID: 35395091). 35395091
FLT3 exon 14 ins FLT3 Y693N hematologic cancer predicted - resistant Midostaurin Preclinical - Cell culture Actionable In a preclinical study, transformed hematologic cells expressing FLT3-ITD and FLT3 Y693N were moderately resistant to Rydapt (midostaurin) treatment in culture (PMID: 35395091). 35395091
FLT3 exon 14 ins FLT3 D835Y hematologic cancer sensitive Gilteritinib Preclinical - Cell culture Actionable In a preclinical study, Xospata (gilteritinib) treatment inhibited growth of transformed hematologic cells expressing FLT3-ITD and FLT3 D835Y in culture (PMID: 35395091). 35395091
FLT3 exon 14 ins FLT3 F691L hematologic cancer resistant Gilteritinib Preclinical - Cell culture Actionable In a preclinical study, transformed hematologic cells expressing FLT3-ITD and FLT3 F691L were moderately resistant to Xospata (gilteritinib) treatment in culture (PMID: 35395091). 35395091
FLT3 exon 14 ins FLT3 C828S hematologic cancer sensitive FF-10101 Preclinical - Cell culture Actionable In a preclinical study, FF-10101 treatment inhibited growth of transformed hematologic cells expressing FLT3-ITD and FLT3 C828S in culture (PMID: 35395091). 35395091
FLT3 exon 14 ins FLT3 D835A hematologic cancer sensitive Crenolanib Preclinical - Cell culture Actionable In a preclinical study, Crenolanib (CP-868596) treatment inhibited growth of transformed hematologic cells expressing FLT3-ITD and FLT3 D835A in culture (PMID: 35395091). 35395091
FLT3 exon 14 ins FLT3 M664I hematologic cancer sensitive FF-10101 Preclinical - Cell culture Actionable In a preclinical study, FF-10101 treatment inhibited growth of transformed hematologic cells expressing FLT3-ITD and FLT3 M664I in culture (PMID: 35395091). 35395091
FLT3 exon 14 ins FLT3 C790S hematologic cancer sensitive FF-10101 Preclinical - Cell culture Actionable In a preclinical study, FF-10101 treatment inhibited growth of transformed hematologic cells expressing FLT3-ITD and FLT3 C790S in culture (PMID: 35395091). 35395091
FLT3 exon 14 ins NRAS Q61K acute myeloid leukemia resistant FF-10101 Preclinical - Cell culture Actionable In a preclinical study, acute myeloid leukemia cells harboring a FLT3-ITD mutation and expressing NRAS Q61K demonstrated resistance to treatment with FF-10101 in culture (PMID: 35395091). 35395091
FLT3 exon 14 ins FLT3 K429E hematologic cancer sensitive Quizartinib Preclinical - Cell culture Actionable In a preclinical study, Vanflyta (quizartinib) treatment inhibited growth of transformed hematologic cells expressing FLT3-ITD and FLT3 K429E in culture (PMID: 35395091). 35395091
FLT3 exon 14 ins FLT3 D835Y hematologic cancer sensitive FF-10101 Preclinical - Cell culture Actionable In a preclinical study, FF-10101 treatment inhibited growth of transformed hematologic cells expressing FLT3-ITD and FLT3 D835Y in culture (PMID: 35395091). 35395091
FLT3 exon 14 ins FLT3 D835I hematologic cancer sensitive Midostaurin Preclinical - Cell culture Actionable In a preclinical study, Rydapt (midostaurin) treatment inhibited growth of transformed hematologic cells expressing FLT3-ITD and FLT3 D835I in culture (PMID: 35395091). 35395091
FLT3 exon 14 ins hematologic cancer sensitive Quizartinib Preclinical - Cell culture Actionable In a preclinical study, Vanflyta (quizartinib) treatment inhibited growth of transformed hematologic cells expressing FLT3-ITD in culture (PMID: 35395091). 35395091
FLT3 exon 14 ins hematologic cancer sensitive Midostaurin Preclinical - Cell culture Actionable In a preclinical study, Rydapt (midostaurin) treatment inhibited growth of transformed hematologic cells expressing a FLT3-ITD mutation in culture (PMID: 35395091). 35395091
FLT3 exon 14 ins FLT3 D698N hematologic cancer sensitive Quizartinib Preclinical - Cell culture Actionable In a preclinical study, Vanflyta (quizartinib) treatment inhibited growth of transformed hematologic cells expressing FLT3-ITD and FLT3 D698N in culture (PMID: 35395091). 35395091
FLT3 exon 14 ins FLT3 Y693C hematologic cancer sensitive Quizartinib Preclinical - Cell culture Actionable In a preclinical study, Vanflyta (quizartinib) treatment inhibited growth of transformed hematologic cells expressing FLT3-ITD and FLT3 Y693C in culture (PMID: 35395091). 35395091
FLT3 exon 14 ins FLT3 Y842C acute myeloid leukemia sensitive FF-10101 Preclinical - Cell culture Actionable In a preclinical study, FF-10101 treatment inhibited growth of acute myeloid leukemia cells harboring FLT3-ITD and FLT3 Y842C in culture (PMID: 35395091). 35395091
FLT3 exon 14 ins FLT3 G697S hematologic cancer predicted - resistant Midostaurin Preclinical - Cell culture Actionable In a preclinical study, transformed hematologic cells expressing FLT3-ITD and FLT3 G697S were moderately resistant to Rydapt (midostaurin) treatment in culture (PMID: 35395091). 35395091
FLT3 exon 14 ins FLT3 D835V acute myeloid leukemia sensitive FF-10101 Preclinical - Cell culture Actionable In a preclinical study, FF-10101 treatment inhibited growth of acute myeloid leukemia cells harboring FLT3-ITD and FLT3 D835V in culture (PMID: 35395091). 35395091
FLT3 exon 14 ins FLT3 D835I hematologic cancer sensitive FF-10101 Preclinical - Cell culture Actionable In a preclinical study, FF-10101 treatment inhibited growth of transformed hematologic cells expressing FLT3-ITD and FLT3 D835I in culture (PMID: 35395091). 35395091
FLT3 exon 14 ins FLT3 D835F hematologic cancer sensitive Midostaurin Preclinical - Cell culture Actionable In a preclinical study, Rydapt (midostaurin) treatment inhibited growth of transformed hematologic cells expressing FLT3-ITD and FLT3 D835F in culture (PMID: 35395091). 35395091
FLT3 exon 14 ins NRAS G12C acute myeloid leukemia resistant FF-10101 Preclinical - Cell culture Actionable In a preclinical study, acute myeloid leukemia cells harboring a FLT3-ITD mutation and expressing NRAS G12C demonstrated resistance to treatment with FF-10101 in culture (PMID: 35395091). 35395091
FLT3 exon 14 ins FLT3 N841Y acute myeloid leukemia sensitive FF-10101 Preclinical - Cell culture Actionable In a preclinical study, FF-10101 treatment inhibited growth of acute myeloid leukemia cells harboring FLT3-ITD and FLT3 N841Y in culture (PMID: 35395091). 35395091
FLT3 exon 14 ins FLT3 D835I hematologic cancer sensitive Crenolanib Preclinical - Cell culture Actionable In a preclinical study, Crenolanib (CP-868596) treatment inhibited growth of transformed hematologic cells expressing FLT3-ITD and FLT3 D835I in culture (PMID: 35395091). 35395091
FLT3 exon 14 ins FLT3 D835N hematologic cancer sensitive FF-10101 Preclinical - Cell culture Actionable In a preclinical study, FF-10101 treatment inhibited growth of transformed hematologic cells expressing FLT3-ITD and FLT3 D835N in culture (PMID: 35395091). 35395091
FLT3 exon 14 ins FLT3 D835G hematologic cancer sensitive Midostaurin Preclinical - Cell culture Actionable In a preclinical study, Rydapt (midostaurin) treatment inhibited growth of transformed hematologic cells expressing FLT3-ITD and FLT3 D835G in culture (PMID: 35395091). 35395091
FLT3 exon 14 ins FLT3 D835del hematologic cancer sensitive FF-10101 Preclinical - Cell culture Actionable In a preclinical study, FF-10101 treatment inhibited growth of transformed hematologic cells expressing FLT3-ITD and FLT3 D835del in culture (PMID: 35395091). 35395091
FLT3 exon 14 ins FLT3 D835H hematologic cancer predicted - resistant Quizartinib Preclinical - Cell culture Actionable In a preclinical study, transformed hematologic cells expressing FLT3-ITD and FLT3 D835H were moderately resistant to treatment with Vanflyta (quizartinib) in culture (PMID: 35395091). 35395091
FLT3 exon 14 ins FLT3 K429E hematologic cancer sensitive Crenolanib Preclinical - Cell culture Actionable In a preclinical study, Crenolanib (CP-868596) treatment inhibited growth of transformed hematologic cells expressing FLT3-ITD and FLT3 K429E in culture (PMID: 35395091). 35395091
FLT3 exon 14 ins FLT3 Y693N hematologic cancer predicted - resistant FF-10101 Preclinical - Cell culture Actionable In a preclinical study, transformed hematologic cells expressing FLT3-ITD and FLT3 Y693N were moderately resistant to treatment with FF-10101 in culture (PMID: 35395091). 35395091
FLT3 exon 14 ins FLT3 Y693C hematologic cancer resistant Gilteritinib Preclinical - Cell culture Actionable In a preclinical study, transformed hematologic cells expressing FLT3-ITD and FLT3 Y693C were moderately resistant to Xospata (gilteritinib) treatment in culture (PMID: 35395091). 35395091
FLT3 exon 14 ins FLT3 D835A hematologic cancer sensitive Quizartinib Preclinical - Cell culture Actionable In a preclinical study, Vanflyta (quizartinib) treatment inhibited growth of transformed hematologic cells expressing FLT3-ITD and FLT3 D835A in culture (PMID: 35395091). 35395091
FLT3 exon 14 ins FLT3 D835H hematologic cancer sensitive FF-10101 Preclinical - Cell culture Actionable In a preclinical study, FF-10101 treatment inhibited growth of transformed hematologic cells expressing FLT3-ITD and FLT3 D835H in culture (PMID: 35395091). 35395091
FLT3 exon 14 ins FLT3 G697S hematologic cancer predicted - resistant Quizartinib Preclinical - Cell culture Actionable In a preclinical study, transformed hematologic cells expressing FLT3-ITD and FLT3 G697S were moderately resistant to Vanflyta (quizartinib) treatment in culture (PMID: 35395091). 35395091
FLT3 exon 14 ins FLT3 D835Y hematologic cancer sensitive Crenolanib Preclinical - Cell culture Actionable In a preclinical study, Crenolanib (CP-868596) treatment inhibited growth of transformed hematologic cells expressing FLT3-ITD and FLT3 D835Y in culture (PMID: 35395091). 35395091
FLT3 exon 14 ins hematologic cancer sensitive FF-10101 Preclinical - Cell culture Actionable In a preclinical study, FF-10101 treatment inhibited growth of transformed hematologic cells expressing FLT3-ITD in culture (PMID: 35395091). 35395091
FLT3 exon 14 ins FLT3 D835A hematologic cancer predicted - sensitive Midostaurin Preclinical - Cell culture Actionable In a preclinical study, Rydapt (midostaurin) treatment inhibited growth of transformed hematologic cells expressing FLT3-ITD and FLT3 D835A in culture (PMID: 35395091). 35395091
FLT3 exon 14 ins FLT3 D835F hematologic cancer resistant Quizartinib Preclinical - Cell culture Actionable In a preclinical study, transformed hematologic cells expressing FLT3-ITD and FLT3 D835F were resistant to treatment with Vanflyta (quizartinib) in culture (PMID: 35395091). 35395091
FLT3 exon 14 ins FLT3 Y693C FLT3 D835V hematologic cancer resistant FF-10101 Preclinical - Cell culture Actionable In a preclinical study, transformed hematologic cells expressing FLT3-ITD with FLT3 Y693C and D835V were resistant to treatment with FF-10101 in culture (PMID: 35395091). 35395091
FLT3 exon 14 ins FLT3 D835Y hematologic cancer resistant Quizartinib Preclinical - Cell culture Actionable In a preclinical study, transformed hematologic cells expressing FLT3-ITD and FLT3 D835Y were resistant to treatment with Vanflyta (quizartinib) in culture (PMID: 35395091). 35395091
FLT3 exon 14 ins FLT3 Y693N hematologic cancer sensitive Quizartinib Preclinical - Cell culture Actionable In a preclinical study, Vanflyta (quizartinib) treatment inhibited growth of transformed hematologic cells expressing FLT3-ITD and FLT3 Y693N in culture (PMID: 35395091). 35395091
FLT3 exon 14 ins NRAS Q61K acute myeloid leukemia predicted - sensitive FF-10101 + Trametinib Preclinical - Cell culture Actionable In a preclinical study, treatment with the combination of FF-10101 and Mekinist (trametinib) resulted in decreased viability of acute myeloid leukemia cells harboring a FLT3-ITD mutation and expressing NRAS Q61K compared to treatment with FF-10101 alone in culture (PMID: 35395091). 35395091
FLT3 exon 14 ins FLT3 N841K acute myeloid leukemia sensitive FF-10101 Preclinical - Cell culture Actionable In a preclinical study, FF-10101 treatment inhibited growth of acute myeloid leukemia cells harboring FLT3-ITD and FLT3 N841K in culture (PMID: 35395091). 35395091
FLT3 exon 14 ins FLT3 D835del hematologic cancer sensitive Gilteritinib Preclinical - Cell culture Actionable In a preclinical study, Xospata (gilteritinib) treatment inhibited growth of transformed hematologic cells expressing FLT3-ITD and FLT3 D835del in culture (PMID: 35395091). 35395091
FLT3 exon 14 ins FLT3 D835F hematologic cancer sensitive Gilteritinib Preclinical - Cell culture Actionable In a preclinical study, Xospata (gilteritinib) treatment inhibited growth of transformed hematologic cells expressing FLT3-ITD and FLT3 D835F in culture (PMID: 35395091). 35395091
FLT3 exon 14 ins FLT3 D835N hematologic cancer sensitive Quizartinib Preclinical - Cell culture Actionable In a preclinical study, Vanflyta (quizartinib) treatment inhibited growth of transformed hematologic cells expressing FLT3-ITD and FLT3 D835N in culture (PMID: 35395091). 35395091
FLT3 exon 14 ins FLT3 D835N hematologic cancer sensitive Crenolanib Preclinical - Cell culture Actionable In a preclinical study, Crenolanib (CP-868596) treatment inhibited growth of transformed hematologic cells expressing FLT3-ITD and FLT3 D835N in culture (PMID: 35395091). 35395091
FLT3 exon 14 ins FLT3 D835H acute myeloid leukemia sensitive FF-10101 Preclinical - Cell culture Actionable In a preclinical study, FF-10101 treatment inhibited growth of acute myeloid leukemia cells harboring FLT3-ITD and FLT3 D835H in culture (PMID: 35395091). 35395091
FLT3 exon 14 ins FLT3 D835A hematologic cancer sensitive Gilteritinib Preclinical - Cell culture Actionable In a preclinical study, Xospata (gilteritinib) treatment inhibited growth of transformed hematologic cells expressing FLT3-ITD and FLT3 D835A in culture (PMID: 35395091). 35395091
FLT3 exon 14 ins FLT3 D835V hematologic cancer resistant Quizartinib Preclinical - Cell culture Actionable In a preclinical study, transformed hematologic cells expressing FLT3-ITD and FLT3 D835V were resistant to treatment with Vanflyta (quizartinib) in culture (PMID: 35395091). 35395091
FLT3 exon 14 ins FLT3 Y693F hematologic cancer sensitive FF-10101 Preclinical - Cell culture Actionable In a preclinical study, FF-10101 treatment inhibited growth of transformed hematologic cells expressing FLT3-ITD and FLT3 Y693F in culture (PMID: 35395091). 35395091
FLT3 exon 14 ins FLT3 G697S hematologic cancer predicted - resistant Crenolanib Preclinical - Cell culture Actionable In a preclinical study, transformed hematologic cells expressing FLT3-ITD and FLT3 G697S were moderately resistant to Crenolanib (CP-868596) treatment in culture (PMID: 35395091). 35395091
FLT3 exon 14 ins FLT3 D835V hematologic cancer sensitive Crenolanib Preclinical - Cell culture Actionable In a preclinical study, Crenolanib (CP-868596) treatment inhibited growth of transformed hematologic cells expressing FLT3-ITD and FLT3 D835V in culture (PMID: 35395091). 35395091
FLT3 exon 14 ins FLT3 D835Y hematologic cancer sensitive Midostaurin Preclinical - Cell culture Actionable In a preclinical study, Rydapt (midostaurin) treatment inhibited growth of transformed hematologic cells expressing FLT3-ITD and FLT3 D835Y in culture (PMID: 35395091). 35395091
FLT3 exon 14 ins FLT3 D835E hematologic cancer sensitive FF-10101 Preclinical - Cell culture Actionable In a preclinical study, FF-10101 treatment inhibited growth of transformed hematologic cells expressing FLT3-ITD and FLT3 D835E in culture (PMID: 35395091). 35395091
FLT3 exon 14 ins FLT3 F691L FLT3 D835V hematologic cancer predicted - resistant FF-10101 Preclinical - Cell culture Actionable In a preclinical study, transformed hematologic cells expressing FLT3-ITD with FLT3 F691L and D835V were moderately resistant to treatment with FF-10101 in culture (PMID: 35395091). 35395091
FLT3 exon 14 ins NRAS Q61K acute myeloid leukemia resistant Quizartinib Preclinical - Cell culture Actionable In a preclinical study, acute myeloid leukemia cells harboring a FLT3-ITD mutation and expressing NRAS Q61K demonstrated resistance to treatment with Vanflyta (quizartinib) in culture (PMID: 35395091). 35395091
FLT3 exon 14 ins FLT3 F691L hematologic cancer resistant Midostaurin Preclinical - Cell culture Actionable In a preclinical study, transformed hematologic cells expressing FLT3-ITD and FLT3 F691L were moderately resistant to Rydapt (midostaurin) treatment in culture (PMID: 35395091). 35395091
FLT3 exon 14 ins hematologic cancer sensitive Crenolanib Preclinical - Cell culture Actionable In a preclinical study, Crenolanib (CP-868596) treatment inhibited growth of transformed hematologic cells expressing FLT3-ITD in culture (PMID: 35395091). 35395091
FLT3 exon 14 ins FLT3 D835I hematologic cancer sensitive Gilteritinib Preclinical - Cell culture Actionable In a preclinical study, Xospata (gilteritinib) treatment inhibited growth of transformed hematologic cells expressing FLT3-ITD and FLT3 D835I in culture (PMID: 35395091). 35395091
FLT3 exon 14 ins FLT3 D698N hematologic cancer resistant Gilteritinib Preclinical - Cell culture Actionable In a preclinical study, transformed hematologic cells expressing FLT3-ITD and FLT3 D698N were moderately resistant to Xospata (gilteritinib) treatment in culture (PMID: 35395091). 35395091
FLT3 exon 14 ins FLT3 D835G hematologic cancer sensitive Quizartinib Preclinical - Cell culture Actionable In a preclinical study, Vanflyta (quizartinib) treatment inhibited growth of transformed hematologic cells expressing FLT3-ITD and FLT3 D835G in culture (PMID: 35395091). 35395091
FLT3 exon 14 ins FLT3 N676K hematologic cancer sensitive Midostaurin Preclinical - Cell culture Actionable In a preclinical study, Rydapt (midostaurin) treatment inhibited growth of transformed hematologic cells expressing FLT3-ITD and FLT3 N676K in culture (PMID: 35395091). 35395091
FLT3 exon 14 ins FLT3 D835I hematologic cancer resistant Quizartinib Preclinical - Cell culture Actionable In a preclinical study, transformed hematologic cells expressing FLT3-ITD and FLT3 D835I were resistant to treatment with Vanflyta (quizartinib) in culture (PMID: 35395091). 35395091
FLT3 exon 14 ins FLT3 G697S hematologic cancer predicted - resistant FF-10101 Preclinical - Cell culture Actionable In a preclinical study, transformed hematologic cells expressing FLT3-ITD and FLT3 G697S were moderately resistant to treatment with FF-10101 in culture (PMID: 35395091). 35395091
FLT3 exon 14 ins FLT3 D835A hematologic cancer sensitive FF-10101 Preclinical - Cell culture Actionable In a preclinical study, FF-10101 treatment inhibited growth of transformed hematologic cells expressing FLT3-ITD and FLT3 D835A in culture (PMID: 35395091). 35395091
FLT3 exon 14 ins NRAS G12C acute myeloid leukemia resistant Quizartinib Preclinical - Cell culture Actionable In a preclinical study, acute myeloid leukemia cells harboring a FLT3-ITD mutation and expressing NRAS G12C demonstrated resistance to treatment with Vanflyta (quizartinib) in culture (PMID: 35395091). 35395091
FLT3 exon 14 ins FLT3 D835V hematologic cancer sensitive Gilteritinib Preclinical - Cell culture Actionable In a preclinical study, Xospata (gilteritinib) treatment inhibited growth of transformed hematologic cells expressing FLT3-ITD and FLT3 D835V in culture (PMID: 35395091). 35395091
FLT3 exon 14 ins FLT3 K429E hematologic cancer sensitive Gilteritinib Preclinical - Cell culture Actionable In a preclinical study, Xospata (gilteritinib) treatment inhibited growth of transformed hematologic cells expressing FLT3-ITD and FLT3 K429E in culture (PMID: 35395091). 35395091
FLT3 exon 14 ins FLT3 Y693C hematologic cancer resistant FF-10101 Preclinical - Cell culture Actionable In a preclinical study, transformed hematologic cells expressing FLT3-ITD and FLT3 Y693C were resistant to treatment with FF-10101 in culture (PMID: 35395091). 35395091
FLT3 exon 14 ins FLT3 D698N hematologic cancer predicted - resistant Midostaurin Preclinical - Cell culture Actionable In a preclinical study, transformed hematologic cells expressing FLT3-ITD and FLT3 D698N were moderately resistant to Rydapt (midostaurin) treatment in culture (PMID: 35395091). 35395091
FLT3 exon 14 ins acute myeloid leukemia sensitive FF-10101 Preclinical - Cell culture Actionable In a preclinical study, FF-10101 treatment inhibited growth of acute myeloid leukemia cells harboring FLT3-ITD in culture (PMID: 35395091). 35395091
FLT3 exon 14 ins FLT3 C807S hematologic cancer sensitive FF-10101 Preclinical - Cell culture Actionable In a preclinical study, FF-10101 treatment inhibited growth of transformed hematologic cells expressing FLT3-ITD and FLT3 C807S in culture (PMID: 35395091). 35395091
FLT3 exon 14 ins FLT3 F691L hematologic cancer predicted - resistant Quizartinib Preclinical - Cell culture Actionable In a preclinical study, transformed hematologic cells expressing FLT3-ITD and FLT3 F691L were resistant to Vanflyta (quizartinib) treatment in culture (PMID: 35395091). 35395091
FLT3 exon 14 ins FLT3 Y693N hematologic cancer predicted - resistant Crenolanib Preclinical - Cell culture Actionable In a preclinical study, transformed hematologic cells expressing FLT3-ITD and FLT3 Y693N were moderately resistant to Crenolanib (CP-868596) treatment in culture (PMID: 35395091). 35395091
FLT3 exon 14 ins NRAS G12C acute myeloid leukemia predicted - sensitive FF-10101 + Trametinib Preclinical - Cell culture Actionable In a preclinical study, treatment with the combination of FF-10101 and Mekinist (trametinib) resulted in decreased viability of acute myeloid leukemia cells harboring a FLT3-ITD mutation and expressing NRAS G12C compared to treatment with FF-10101 alone in culture (PMID: 35395091). 35395091
FLT3 exon 14 ins FLT3 N676K hematologic cancer sensitive Crenolanib Preclinical - Cell culture Actionable In a preclinical study, Crenolanib (CP-868596) treatment inhibited growth of transformed hematologic cells expressing FLT3-ITD and FLT3 N676K in culture (PMID: 35395091). 35395091
FLT3 exon 14 ins FLT3 D698N FLT3 D835V hematologic cancer predicted - resistant FF-10101 Preclinical - Cell culture Actionable In a preclinical study, transformed hematologic cells expressing FLT3-ITD with FLT3 D698N and D835V were moderately resistant to treatment with FF-10101 in culture (PMID: 35395091). 35395091
FLT3 exon 14 ins FLT3 D835V hematologic cancer sensitive FF-10101 Preclinical - Cell culture Actionable In a preclinical study, FF-10101 treatment inhibited growth of transformed hematologic cells expressing FLT3-ITD and FLT3 D835V in culture (PMID: 35395091). 35395091
FLT3 exon 14 ins FLT3 D835F hematologic cancer sensitive Crenolanib Preclinical - Cell culture Actionable In a preclinical study, Crenolanib (CP-868596) treatment inhibited growth of transformed hematologic cells expressing FLT3-ITD and FLT3 D835F in culture (PMID: 35395091). 35395091
FLT3 exon 14 ins FLT3 D835Y acute myeloid leukemia sensitive FF-10101 Preclinical - Cell culture Actionable In a preclinical study, FF-10101 treatment inhibited growth of acute myeloid leukemia cells harboring FLT3-ITD and FLT3 D835Y in culture (PMID: 35395091). 35395091
FLT3 exon 14 ins FLT3 F691L hematologic cancer sensitive FF-10101 Preclinical - Cell culture Actionable In a preclinical study, transformed hematologic cells harboring FLT3-ITD and FLT3 F691L demonstrated sensitivity to treatment with FF-10101 in culture, but were less sensitive compared to cells expressing FLT3-ITD alone (PMID: 35395091). 35395091
FLT3 exon 14 ins FLT3 G697S hematologic cancer resistant Gilteritinib Preclinical - Cell culture Actionable In a preclinical study, transformed hematologic cells expressing FLT3-ITD and FLT3 G697S were resistant to Xospata (gilteritinib) treatment in culture (PMID: 35395091). 35395091
FLT3 exon 14 ins FLT3 C694S hematologic cancer sensitive FF-10101 Preclinical - Cell culture Actionable In a preclinical study, FF-10101 treatment inhibited growth of transformed hematologic cells expressing FLT3-ITD and FLT3 C694S in culture (PMID: 35395091). 35395091