|Peptide substrates to sensitively and specifically measure the real-time activity of FLT3, a kinase linked to acute myeloid leukemia.|
- Clinical diagnostic to determine AML behavior and optimal treatment strategy
- Oncology research on mechanism of resistance development in cancers (specifically AML)
- Chemotherapeutic drug identification and development
- Basic kinase research
Key Benefits & Differentiators
- Highly selective and specific: Perform 200% better compared to the currently available FLT3 substrate, capable of providing real-time activity measurements in live cells.
- Multiple readouts amenable to high throughput assays: Phosphorylation of the substrate can be measured using ELISA, mass spectrometry, or through incorporation of terbium binding segments eliciting a fluorescent readout.
- Use with wild-type, unmodified kinases: Does not require the modification or tagging of kinases prior to experimentation.
FLT3’s heavy role in AML
Fms-like tyrosine kinase 3 (FLT3) kinase is one of the most frequently mutated genes in acute myeloid leukemia (AML). Early studies have shown that mutations in FLT3 are correlated with poor long-term prognosis with increased risk for relapse. To assess FLT3 activity, Laurie Parker’s lab at the University of Minnesota designed substrates phosphorylated by FLT3 in a manner that is highly efficient and specific. Coupled with fluorescent and/or mass spectrometric readouts, these peptides are valuable tools in both drug discovery and diagnostics for FLT3-linked AML.
Measuring FLT3 activity to develop diagnostics and discover therapeutics
The developed FLT3 artificial substrates (FAS-A) is compatible with living cells and facilitates rapid detection of kinase activity in real time. When compared to alternatives, FAS-A is phosphorylated 200% more effectively than the only other FLT3 substrate reported in the literature (FLT3tide). Due to its high selectivity, FAS-A can be used in complex lysates or mixtures and with negligible off-target effects and can be multiplexed with other assays. Finally, the phosphorylation of the substrate can be measured using ELISA, mass spectrometry, or through incorporation of terbium binding segments, facilitating a fluorescent readout. This flexibility facilitates the use of the substrate in a wide variety of applications including high-throughput and drug discovery methods.
Phase of Development
Multiple designed substrates of wildtype and mutant forms of FLT3 assessed in vitro.
Seeking Industry Partners
This technology is now available for:
- Sponsored research
- Collaborative development
Please contact Kenneth Karanja to share your business’ needs and learn more.
- "High-throughput Identification of FLT3 Wild-type and Mutant Kinase Substrate Preferences and Application to Design of Sensitive In Vitro Kinase Assay Substrates" Molecular and Cellular Proteomics, 2019