Resistance mutation info of target

Target General Information
Target ID T74312
Target Name Receptor-type tyrosine-protein kinase (FLT3) Target Info
Gene Name FLT3
Species Homo sapiens
Uniprot ID FLT3_HUMAN
Sequence MPALARDGGQLPLLVVFSAMIFGTITNQDLPVIKCVLINHKNNDSSVGKSSSYPMVSESP
EDLGCALRPQSSGTVYEAAAVEVDVSASITLQVLVDAPGNISCLWVFKHSSLNCQPHFDL
QNRGVVSMVILKMTETQAGEYLLFIQSEATNYTILFTVSIRNTLLYTLRRPYFRKMENQD
ALVCISESVPEPIVEWVLCDSQGESCKEESPAVVKKEEKVLHELFGTDIRCCARNELGRE
CTRLFTIDLNQTPQTTLPQLFLKVGEPLWIRCKAVHVNHGFGLTWELENKALEEGNYFEM
STYSTNRTMIRILFAFVSSVARNDTGYYTCSSSKHPSQSALVTIVEKGFINATNSSEDYE
IDQYEEFCFSVRFKAYPQIRCTWTFSRKSFPCEQKGLDNGYSISKFCNHKHQPGEYIFHA
ENDDAQFTKMFTLNIRRKPQVLAEASASQASCFSDGYPLPSWTWKKCSDKSPNCTEEITE
GVWNRKANRKVFGQWVSSSTLNMSEAIKGFLVKCCAYNSLGTSCETILLNSPGPFPFIQD
NISFYATIGVCLLFIVVLTLLICHKYKKQFRYESQLQMVQVTGSSDNEYFYVDFREYEYD
LKWEFPRENLEFGKVLGSGAFGKVMNATAYGISKTGVSIQVAVKMLKEKADSSEREALMS
ELKMMTQLGSHENIVNLLGACTLSGPIYLIFEYCCYGDLLNYLRSKREKFHRTWTEIFKE
HNFSFYPTFQSHPNSSMPGSREVQIHPDSDQISGLHGNSFHSEDEIEYENQKRLEEEEDL
NVLTFEDLLCFAYQVAKGMEFLEFKSCVHRDLAARNVLVTHGKVVKICDFGLARDIMSDS
NYVVRGNARLPVKWMAPESLFEGIYTIKSDVWSYGILLWEIFSLGVNPYPGIPVDANFYK
LIQNGFKMDQPFYATEEIYIIMQSCWAFDSRKRPSFPNLTSFLGCQLADAEEAMYQNVDG
RVSECPHTYQNRRPFSREMDLGLLSPQAQVEDS [Homo sapiens]
Drug Resistance Mutation and Corresponding Drugs
Ref 528230Sorafenib (BAY 43-9006, Nexavar), a dual-action inhibitor that targets RAF/MEK/ERK pathway in tumor cells and tyrosine kinases VEGFR/PDGFR in tumor vasculature. Methods Enzymol. 2006;407:597-612.
Ref 541050(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 5711).
Ref 5287152006 drug approvals: finding the niche. Nat Rev Drug Discov. 2007 Feb;6(2):99-101.
Ref 537114Emerging therapies for multiple myeloma. Expert Opin Emerg Drugs. 2009 Mar;14(1):99-127.
Ref 541052(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 5713).
Ref 524603ClinicalTrials.gov (NCT02039726) An Open-label Study of Quizartinib Monotherapy vs. Salvage Chemotherapy in Acute Myeloid Leukemia (AML) Subjects. U.S. National Institutes of Health.
Mutation Info Missense: D835F
Drugs
Drug Name Quizartinib Drug Info [555855]
Targeted Disease Acute Myeloid Leukaemia
Mutation Info Missense: D835H
Drugs
Drug Name Sorafenib Drug Info [555847], [555964]
Targeted Disease Acute Myeloid Leukaemia
Mutation Prevalence 4 out of 13 patients
Mutation Info Missense: D835V
Drugs
Drug Name Quizartinib Drug Info [555855]
Targeted Disease Acute Myeloid Leukaemia
Mutation Info Missense: D835Y
Drugs
Drug Name Sunitinib Drug Info [555964]
Targeted Disease Acute Myeloid Leukaemia
Mutation Prevalence 1 out of 6 patients
Drug Name Sorafenib Drug Info [555847]
Targeted Disease Acute Myeloid Leukaemia
Drug Name Quizartinib Drug Info [555846], [555855]
Targeted Disease Acute Myeloid Leukaemia
Mutation Info Missense: F691L
Drugs
Drug Name Sorafenib Drug Info [555964]
Targeted Disease Acute Myeloid Leukaemia
Mutation Prevalence 2 out of 6 patients
Drug Name Quizartinib Drug Info [555855], [555920]
Targeted Disease Acute Myeloid Leukaemia
Reference
Ref 555846Selective FLT3 inhibition of FLT3-ITD+ acute myeloid leukaemia resulting in secondary D835Y mutation: a model for emerging clinical resistance patterns. Leukemia. 2012 Jul;26(7):1462-70. doi: 10.1038/leu.2012.52. Epub 2012 Feb 22.
Ref 555847Sorafenib treatment of FLT3-ITD(+) acute myeloid leukemia: favorable initial outcome and mechanisms of subsequent nonresponsiveness associated with the emergence of a D835 mutation. Blood. 2012 May 31;119(22):5133-43. doi: 10.1182/blood-2011-06-363960. Epub 2012 Feb 24.
Ref 555855Validation of ITD mutations in FLT3 as a therapeutic target in human acute myeloid leukaemia. Nature. 2012 Apr 15;485(7397):260-3. doi: 10.1038/nature11016.
Ref 555920The secondary FLT3-ITD F691L mutation induces resistance to AC220 in FLT3-ITD+ AML but retains in vitro sensitivity to PKC412 and Sunitinib. Leukemia. 2013 Jun;27(6):1416-8. doi: 10.1038/leu.2013.14. Epub 2013 Jan 16.
Ref 555964Emergence of polyclonal FLT3 tyrosine kinase domain mutations during sequential therapy with sorafenib and sunitinib in FLT3-ITD-positive acute myeloid leukemia. Clin Cancer Res. 2013 Oct 15;19(20):5758-68. doi: 10.1158/1078-0432.CCR-13-1323. Epub 2013 Aug 22.

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