Therapeutic Targets Database
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TTD Target ID: TTDS00090

Target Information
NameFL cytokine receptor    
Type of targetSuccessful target    
SynonymsCD135 antigen    
FLT3 tyrosine kinase    
Receptor tyrosine kinase FLT3    
STK-1    
Stem cell tyrosine kinase 1    
Tyrosine-protein kinase receptor FLT3    
DiseaseAcute myeloid leukemia
[ICD9: 205.0   ICD10: C92.0]
[1][2]
Autoimmune diseases
[ICD9: 279.4   ICD10: D84.9, M35.9]
[3]
MLL-rearranged acute lymphoblastic leukemias
[ICD9: 204.0, 208.9   ICD10: C91-C95, C91.0]
[4][5]
Drug(s)PonatinibApprovedChronic, accelerated or blast-phase chronic myeloid leukaemia
SunitinibLaunchedAdvanced renal cell carcinoma[6][7][8][9]
Sunitinib malatePhase IVMetastatic Renal Cell Carcinoma; Gastrointestinal Stromal Tumors[10][11][8]
PacritinibPhase IIIMyelofibrosis (see also lymphoma)
MidostaurinPhase IIColon, breast, CLL, AML, GIST, solid tumours & non-Hodgkin's lymphoma[8][12]
PLX3397Phase IIAcute myeloid leukemia
PLX3397Phase IIGlioblastoma
PLX3397Phase IIGlioblastoma (GBM)
PLX3397Phase IIHodgkin lymphoma
PLX3397Phase IIMetastatic Breast cancer
PLX3397Phase IIMetastatic Prostate cancer
PLX3397Phase IIProstate Caner
QuizartinibPhase IIRelapsed/refractory AML
SunitinibPhase IIAdvanced renal cell carcinoma[6][7][8][9]
Sunitinib malatePhase IISoft Tissue Sarcoma[10][11][8]
TandutinibPhase IIGlioblatoma; Gliosarcoma; Anaplastic Astrocytoma; Anaplastic Oligodendroglioma; Anaplastic Mixed Oligoastrocytoma[8][13]
PLX3397Phase I/IIAcute myelogenous lymphoma (AML)
SU5614Phase I/IIAirway inflammation[7]
4SC-203Phase ISolid tumors[14]
CDX-301Phase IHSC transplantation
MidostaurinPhase IBreast & colorectal cancer[8][12]
TandutinibWithdrawnAcute Myelogenous Leukemia[8][13]
BioChemical ClassTransferases transferring phosphorus-containing groups    
EC NumberEC 2.7.1.112
PathwayAcute myeloid leukemia
Cytokine-cytokine receptor interaction
Hematopoietic cell lineage
Pathways in cancer
UniProt IDP36888
PDB Structure1RJB; 3QS7; 3QS9.    
FunctionReceptor for the fl cytokine, and has a tyrosine-protein kinase activity.    
SequenceMPALARDGGQLPLLVVFSAMIFGTITNQDLPVIKCVLINHKNNDSSVGKSSSYPMVSESP EDLGCALRPQSSGTVYEAAAVEVDVSASITLQVLVDAPGNISCLWVFKHSSLNCQPHFDL QNRGVVSMVILKMTETQAGEYLLFIQSEATNYTILFTVSIRNTLLYTLRRPYFRKMENQD ALVCISESVPEPIVEWVLCDSQGESCKEESPAVVKKEEKVLHELFGTDIRCCARNELGRE CTRLFTIDLNQTPQTTLPQLFLKVGEPLWIRCKAVHVNHGFGLTWELENKALEEGNYFEM STYSTNRTMIRILFAFVSSVARNDTGYYTCSSSKHPSQSALVTIVEKGFINATNSSEDYE IDQYEEFCFSVRFKAYPQIRCTWTFSRKSFPCEQKGLDNGYSISKFCNHKHQPGEYIFHA ENDDAQFTKMFTLNIRRKPQVLAEASASQASCFSDGYPLPSWTWKKCSDKSPNCTEEITE GVWNRKANRKVFGQWVSSSTLNMSEAIKGFLVKCCAYNSLGTSCETILLNSPGPFPFIQD NISFYATIGVCLLFIVVLTLLICHKYKKQFRYESQLQMVQVTGSSDNEYFYVDFREYEYD LKWEFPRENLEFGKVLGSGAFGKVMNATAYGISKTGVSIQVAVKMLKEKADSSEREALMS ELKMMTQLGSHENIVNLLGACTLSGPIYLIFEYCCYGDLLNYLRSKREKFHRTWTEIFKE HNFSFYPTFQSHPNSSMPGSREVQIHPDSDQISGLHGNSFHSEDEIEYENQKRLEEEEDL NVLTFEDLLCFAYQVAKGMEFLEFKSCVHRDLAARNVLVTHGKVVKICDFGLARDIMSDS NYVVRGNARLPVKWMAPESLFEGIYTIKSDVWSYGILLWEIFSLGVNPYPGIPVDANFYK LIQNGFKMDQPFYATEEIYIIMQSCWAFDSRKRPSFPNLTSFLGCQLADAEEAMYQNVDG RVSECPHTYQNRRPFSREMDLGLLSPQAQVEDS
Target ValidationClick to Find Target Validation Information.    
Inhibitor (1H-indol-2-yl)[15]
(1H-indol-2-yl)[15]
(1H-indol-2-yl)[15]
(5-fluoro-1H-indol-2-yl)-[15]
(5-hydroxy-1H-indol-2-yl)[15]
(benzo[b]furan-2-yl)-[16]
2- (3,4-dimethoxybenzamido)thiophene-3-carboxamide[17]
4- (4-aminophenyl)-1H-indazol-3yl-amine[18]
4SC-203[14]
AG1295[16]
Bis- (5-hydroxy-1H-indol-2-yl)-methanone[15]
Ki23819[19]
MLN-518[20]
Midostaurin[8][12]
N-[4- (3-amino-1H-indazol-4-yl)phenyl]benzamide[18]
PKC-412[20]
SU5614[7]
Sunitinib[6][7][8][9]
Sunitinib malate[10][11][8]
Tandutinib[8][13]
bis (5-acetoxybenzo[b]furan-2-yl)methanone[16]
bis (5-aminobenzo[b]furan-2-yl)methanone[16]
bis (5-hydroxybenzo[b]furan-2-yl)methanone[16]
bis (6-hydroxybenzo[b]furan-2-yl)methanone[16]
bis (benzo[b]furan-2-yl)methanone[16]
di (1H-indol-2-yl)methanone[15]
Multitarget4SC-203[14]
Midostaurin[8][12]
Sunitinib[6][7][8][9]
Sunitinib malate[10][11][8]
Cross References 3D Structure
Related Literature
On-Line Medical Dictionary
Ref 1Pediatric AML primary samples with FLT3/ITD mutations are preferentially killed by FLT3 inhibition. Blood. 2004 Sep 15;104(6):1841-9. Epub 2004 May 27. To Reference
Ref 2Mutant FLT3 signaling contributes to a block in myeloid differentiation. Leuk Lymphoma. 2005 Dec;46(12):1679-87. To Reference
Ref 3Inhibition of FLT3 signaling targets DCs to ameliorate autoimmune disease. Proc Natl Acad Sci U S A. 2005 Nov 15;102(46):16741-6. Epub 2005 Nov 4. To Reference
Ref 4Inhibition of FLT3 in MLL. Validation of a therapeutic target identified by gene expression based classification. Cancer Cell. 2003 Feb;3(2):173-83. To Reference
Ref 5Biologic and clinical significance of the FLT3 transcript level in acute myeloid leukemia. Blood. 2004 Mar 1;103(5):1901-8. Epub 2003 Nov 6. To Reference
Ref 6FLT3 inhibition and mechanisms of drug resistance in mutant FLT3-positive AML. Drug Resist Updat. 2009 Jun;12(3):81-9. Epub 2009 May 20. To Reference
Ref 7FMS-like tyrosine kinase 3-internal tandem duplication tyrosine kinase inhibitors display a nonoverlapping profile of resistance mutations in vitro. Cancer Res. 2009 Apr 1;69(7):3032-41. Epub 2009 Mar 24. To Reference
Ref 8A comparison of physicochemical property profiles of marketed oral drugs and orally bioavailable anti-cancer protein kinase inhibitors in clinical development. Curr Top Med Chem. 2007;7(14):1408-22. To Reference
Ref 9Multi-target therapeutics: when the whole is greater than the sum of the parts. Drug Discov Today. 2007 Jan;12(1-2):34-42. Epub 2006 Nov 28. To Reference
Ref 10Pfizer. Product Development Pipeline. March 31 2009. To Reference
Ref 11Sunitinib (Sutent, SU11248), a small-molecule receptor tyrosine kinase inhibitor, blocks function of the ATP-binding cassette (ABC) transporters P-glycoprotein (ABCB1) and ABCG2. Drug Metab Dispos. 2009 Feb;37(2):359-65. Epub 2008 Oct 29. To Reference
Ref 12CBL exon 8/9 mutants activate the FLT3 pathway and cluster in core binding factor/11q deletion acute myeloid leukemia/myelodysplastic syndrome subtypes. Clin Cancer Res. 2009 Apr 1;15(7):2238-47. Epub 2009 Mar 10. To Reference
Ref 13Takeda. Product Development Pipeline. July 31 2009. To Reference
Ref 142011 Pipeline of 4SC AG. To Reference
Ref 15J Med Chem. 2006 Jun 1;49(11):3101-15.Novel bis(1H-indol-2-yl)methanones as potent inhibitors of FLT3 and platelet-derived growth factor receptor tyrosine kinase. To Reference
Ref 16Bioorg Med Chem. 2007 Mar 1;15(5):2187-97. Epub 2006 Dec 12.Inhibition of FLT3 and PDGFR tyrosine kinase activity by bis(benzo[b]furan-2-yl)methanones. To Reference
Ref 17Bioorg Med Chem Lett. 2006 Jun 15;16(12):3282-6. Epub 2006 Mar 31.Identification of 2-acylaminothiophene-3-carboxamides as potent inhibitors of FLT3. To Reference
Ref 18J Med Chem. 2007 Apr 5;50(7):1584-97. Epub 2007 Mar 8.Discovery of N-(4-(3-amino-1H-indazol-4-yl)phenyl)-N'-(2-fluoro-5-methylphenyl)urea (ABT-869), a 3-aminoindazole-based orally active multitargeted receptor tyrosine kinase inhibitor. To Reference
Ref 19Identification of Ki23819, a highly potent inhibitor of kinase activity of mutant FLT3 receptor tyrosine kinase. Leukemia. 2005 Jun;19(6):930-5. To Reference
Ref 20Blood. 2009 Oct 1;114(14):2984-92. Epub 2009 Aug 4.AC220 is a uniquely potent and selective inhibitor of FLT3 for the treatment of acute myeloid leukemia (AML). To Reference



 

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