AC220 is a uniquely potent and selective inhibitor of FLT3 for the treatment of acute myeloid leukemia (AML)
Patrick P. Zarrinkar,Ruwanthi N. Gunawardane,Merryl D. Cramer,Michael F. Gardner,Daniel Brigham,Barbara Belli,Mazen W. Karaman,Keith W. Pratz,Gabriel Pallares,Qi Chao,Kelly G. Sprankle,Hitesh K. Patel,Mark J. Levis,Robert C. Armstrong,Joyce James,Shripad Bhagwat +15 more
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TLDR
The data reveal that the combination of excellent potency, selectivity, and pharmacokinetic properties is unique to AC220, which therefore is the first drug candidate with a profile that matches the characteristics desirable for a clinical FLT3 inhibitor.About:
This article is published in Blood.The article was published on 2009-10-01 and is currently open access. It has received 564 citations till now. The article focuses on the topics: Fms-Like Tyrosine Kinase 3 & Myeloid leukemia.read more
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Patterns of Somatic Mutation in Human Cancer Genomes
TL;DR: In this paper, the coding exons of the family of 518 protein kinases were sequenced in 210 cancers of diverse histological types to explore the nature of the information that will be derived from cancer genome sequencing.
Journal ArticleDOI
Comprehensive analysis of kinase inhibitor selectivity.
Mindy I. Davis,Jeremy P Hunt,Jeremy P Hunt,Sanna Herrgard,Pietro Ciceri,Pietro Ciceri,Lisa M Wodicka,Lisa M Wodicka,Gabriel Pallares,Gabriel Pallares,Michael D. Hocker,Daniel K Treiber,Daniel K Treiber,Patrick P Zarrinkar,Patrick P Zarrinkar +14 more
TL;DR: Analysis of the interaction patterns reveals a class of 'group-selective' inhibitors broadly active against a single subfamily of kinases, but selective outside that subfamily.
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Validation of ITD mutations in FLT3 as a therapeutic target in human acute myeloid leukaemia
Catherine C. Smith,Qi Wang,Chen-Shan Chin,Sara Salerno,Lauren E. Damon,Mark J. Levis,Alexander E. Perl,Kevin Travers,Susana Wang,Jeremy P. Hunt,Jeremy P. Hunt,Patrick P. Zarrinkar,Patrick P. Zarrinkar,Eric E. Schadt,Eric E. Schadt,Andrew Kasarskis,Andrew Kasarskis,John Kuriyan,Neil P. Shah +18 more
TL;DR: It is demonstrated that FLT3-ITD can represent a driver lesion and valid therapeutic target in human AML and AC220-resistant FLT 3 kinase domain mutants represent high-value targets for futureFLT3 inhibitor development efforts.
Journal ArticleDOI
Targeting FLT3 mutations in AML: review of current knowledge and evidence.
TL;DR: This review focuses on the pathological and prognostic role of FLT3 mutations in AML, clinical classification of the disease, recent progress with next-generationFLT3 inhibitors, and mechanisms of resistance to FLT 3 inhibitors.
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Proteolysis-Targeting Chimeras as Therapeutics and Tools for Biological Discovery
George M. Burslem,Craig M. Crews +1 more
TL;DR: The burgeoning field of proteolysis-targeting chimeras (PROTACs), which are capable of modulating protein concentrations at a post-translational level by co-opting the ubiquitin-proteasome system, are described and their application to drug discovery is described.
References
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The Protein Kinase Complement of the Human Genome
TL;DR: The protein kinase complement of the human genome is catalogued using public and proprietary genomic, complementary DNA, and expressed sequence tag sequences to provide a starting point for comprehensive analysis of protein phosphorylation in normal and disease states and a detailed view of the current state of human genome analysis through a focus on one large gene family.
Journal Article
Patterns of Somatic Mutation in Human Cancer Genomes
TL;DR: In this paper, the coding exons of the family of 518 protein kinases were sequenced in 210 cancers of diverse histological types to explore the nature of the information that will be derived from cancer genome sequencing.