Stemcell, 100-1558, Lestaurtinib

Inhibit FMS-like tyrosine kinase 3 (FLT3) activation with Lestaurtinib (IC50 = 2 nM). Mutations in FLT3 cause it to become constitutively active, augmenting activation of downstream signaling pathways, including STAT5, MAPK, and AKT that promote cell growth and inhibit apoptosis. FLT3 mutations are the most frequent genetic alteration associated with acute myeloid leukemia (AML). In primary leukemia blasts from patients with AML and in AML mouse models, Lestaurtinib has been shown to inhibit both FLT3 phosphorylation and activation of its downstream targets (Levis et al. Blood, 2002). Mutations in another tyrosine kinase, Janus kinase 2 (JAK2), are implicated in myeloproliferative disorders; its activity can be similarly inhibited by Lestaurtinib (IC50 = 1 nM) in erythroid cells (Hexner et al. Blood, 2008).

Lestaurtinib has been used for:

CANCER RESEARCH

· Induce a cytotoxic response in human acute myeloid leukemia cell lines and prolong the survival in a leukemia mouse model (Levis et al. Blood, 2002).

· Reduce tumor cell proliferation, increase DNA damage, and induce apoptosis in a medulloblastoma mouse model (Pallavicini et al. Front Oncol, 2023).

· Induce apoptosis in human glioma cell lines and suppress tumor growth in glioma mouse xenograft models (Cao et al. J Cell Mol Med, 2020).

· Reduce viability of human B cell lymphoma (BCL) cells and suppress tumor growth in a BCL mouse xenograft model (Beck et al. J Biol Chem, 2016).