Flt3 mutations are among the most common mutations in acute myeloid leukaemia due to internal tandem duplication of Flt3. The presence of this mutation is a marker of adverse outcome.
Specifically, quizartinib selectively inhibits class III receptor tyrosine kinases, including FMS-related tyrosine kinase 3 (FLT3/STK1), colony-stimulating factor 1 receptor (CSF1R/FMS), stem cell factor receptor (SCFR/KIT), and platelet derived growth factor receptors (PDGFRs).[citation needed]
Mutations cause constant activation of the FLT3 pathway resulting in inhibition of ligand-independent leukemic cell proliferation and apoptosis.[citation needed]
Clinical trials
It reported good results in 2012 from a phase II clinical trial for refractory AML - particularly in patients who went on to have a stem cell transplant.[3]
As of 2017[update], it has completed five clinical trials, and another seven are active.[4]
References
^"Daiichi Sankyo Launches FLT3 Inhibitor VANFLYTA® in Japan for the Treatment of Patients with Relapsed/Refractory FLT3-ITD AML". Retrieved 16 February 2021.
^Chao, Qi; Sprankle, Kelly G.; Grotzfeld, Robert M.; Lai, Andiliy G.; Carter, Todd A.; Velasco, Anne Marie; Gunawardane, Ruwanthi N.; Cramer, Merryl D.; Gardner, Michael F.; James, Joyce; Zarrinkar, Patrick P.; Patel, Hitesh K.; Bhagwat, Shripad S. (2009). "Identification of N-(5-tert-Butyl-isoxazol-3-yl)-N'-{4-[7-(2-morpholin-4-yl-ethoxy)imidazo[2,1-b][1,3]benzothiazol-2-yl]phenyl}urea Dihydrochloride (AC220), a Uniquely Potent, Selective, and Efficacious FMS-Like Tyrosine Kinase-3 (FLT3) Inhibitor". Journal of Medicinal Chemistry. 52 (23): 7808–7816. doi:10.1021/jm9007533. PMID 19754199.
quizartinib, ac220, small, molecule, receptor, tyrosine, kinase, inhibitor, originally, from, ambit, biosciences, later, acquired, daiichi, sankyo, that, currently, under, development, treatment, acute, myeloid, leukaemia, sold, under, brand, name, vanflyta, j. Quizartinib AC220 is a small molecule receptor tyrosine kinase inhibitor originally from Ambit Biosciences and later acquired by Daiichi Sankyo that is currently under development for the treatment of acute myeloid leukaemia Quizartinib is sold under the brand name Vanflyta in Japan 1 Its molecular target is FLT3 also known as CD135 which is a proto oncogene 2 Quizartinib NamesPreferred IUPAC name N 5 tert Butyl 1 2 oxazol 3 yl N 4 7 2 morpholin 4 yl ethoxy imidazo 2 1 b 1 3 benzothiazol 2 yl phenyl ureaOther names AC220 VanflytaIdentifiersCAS Number 950769 58 1 Y PubChem 3D model JSmol Interactive imageChEBI CHEBI 90217 YChEMBL ChEMBL576982 YChemSpider 24640357 YIUPHAR BPS 5658KEGG D09955PubChem CID 24889392UNII 7LA4O6Q0D3 YCompTox Dashboard EPA DTXSID70241746InChI InChI 1S C29H32N6O4S c1 29 2 3 25 17 26 33 39 25 32 27 36 30 20 6 4 19 5 7 20 22 18 35 23 9 8 21 16 24 23 40 28 35 31 22 38 15 12 34 10 13 37 14 11 34 h4 9 16 18H 10 15H2 1 3H3 H2 30 32 33 36 NKey CVWXJKQAOSCOAB UHFFFAOYSA N NInChI 1 C29H32N6O4S c1 29 2 3 25 17 26 33 39 25 32 27 36 30 20 6 4 19 5 7 20 22 18 35 23 9 8 21 16 24 23 40 28 35 31 22 38 15 12 34 10 13 37 14 11 34 h4 9 16 18H 10 15H2 1 3H3 H2 30 32 33 36 Key CVWXJKQAOSCOAB UHFFFAOYAFSMILES CC C C c1cc no1 NC O Nc2ccc cc2 c3cn4c5ccc cc5sc4n3 OCCN6CCOCC6PropertiesChemical formula C 29H 32N 6O 4SMolar mass 560 67 g mol 1PharmacologyATC code L01EX11 WHO Except where otherwise noted data are given for materials in their standard state at 25 C 77 F 100 kPa N verify what is Y N Infobox references Flt3 mutations are among the most common mutations in acute myeloid leukaemia due to internal tandem duplication of Flt3 The presence of this mutation is a marker of adverse outcome Contents 1 Mechanism 2 Clinical trials 3 ReferencesMechanism EditSpecifically quizartinib selectively inhibits class III receptor tyrosine kinases including FMS related tyrosine kinase 3 FLT3 STK1 colony stimulating factor 1 receptor CSF1R FMS stem cell factor receptor SCFR KIT and platelet derived growth factor receptors PDGFRs citation needed Mutations cause constant activation of the FLT3 pathway resulting in inhibition of ligand independent leukemic cell proliferation and apoptosis citation needed Clinical trials EditIt reported good results in 2012 from a phase II clinical trial for refractory AML particularly in patients who went on to have a stem cell transplant 3 As of 2017 update it has completed five clinical trials and another seven are active 4 References Edit Daiichi Sankyo Launches FLT3 Inhibitor VANFLYTA in Japan for the Treatment of Patients with Relapsed Refractory FLT3 ITD AML Retrieved 16 February 2021 Chao Qi Sprankle Kelly G Grotzfeld Robert M Lai Andiliy G Carter Todd A Velasco Anne Marie Gunawardane Ruwanthi N Cramer Merryl D Gardner Michael F James Joyce Zarrinkar Patrick P Patel Hitesh K Bhagwat Shripad S 2009 Identification of N 5 tert Butyl isoxazol 3 yl N 4 7 2 morpholin 4 yl ethoxy imidazo 2 1 b 1 3 benzothiazol 2 yl phenyl urea Dihydrochloride AC220 a Uniquely Potent Selective and Efficacious FMS Like Tyrosine Kinase 3 FLT3 Inhibitor Journal of Medicinal Chemistry 52 23 7808 7816 doi 10 1021 jm9007533 PMID 19754199 Drug Tames Refractory AML ASH Dec 2012 Quizartinib studies Retrieved from https en wikipedia org w index php title Quizartinib amp oldid 1164683317, wikipedia, wiki, book, books, library,
