Nintedanib Targets KIT D816V Neoplastic Cells Derived from Induced Pluripotent Stem cells of Systemic Mastocytosis.

@article{Toledo2020NintedanibTK,
  title={Nintedanib Targets KIT D816V Neoplastic Cells Derived from Induced Pluripotent Stem cells of Systemic Mastocytosis.},
  author={Marcelo A. S. Toledo and Malrun Gatz and Stephanie Sontag and Karoline V Gleixner and Gregor Eisenwort and Kristina Feldberg and Ahmed E. I. Hamouda and Frederick Kluge and Riccardo Guareschi and Giulia Rossetti and Antonio S. Sechi and Olli M. J. Dufva and Satu M. Mustjoki and Angela Maurer and Herdit Monika Sch{\"u}ler and Roman Goetzke and Till Braunschweig and Anne Kaiser and Jens Peter Panse and Mohamad Jawhar and Andreas Reiter and Frank C. Hilberg and Peter Ettmayer and Wolfgang Wagner and Steffen Koschmieder and Tim Henrik Br{\"u}mmendorf and Peter Valent and Nicolas Chatain and Martin Zenke},
  journal={Blood},
  year={2020}
}
The KIT D816V mutation is found in more than 80% of patients with systemic mastocytosis (SM) and is key to neoplastic mast cell (MC) expansion and accumulation in affected organs. KIT D816V therefore represents a prime therapeutic target for SM. Here we generated a panel of patient-specific KIT D816V induced pluripotent stem cells (iPSCs) from patients with aggressive SM (ASM) and mast cell leukemia (MCL) to develop a patient-specific SM disease model for mechanistic and drug discovery studies… 
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TLDR
DCC-2618 is a spectrum-selective pan KIT and PDGFRA inhibitor which blocks KIT D816V and multiple other kinase targets relevant to systemic mastocytosis and inhibits growth, survival and activation of multiple cell types relevant to advanced systemic mastocrytosis.
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TLDR
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TLDR
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