NCIt definition : An orally bioavailable indolocarbazole derivative and inhibitor of constitutively
active mutant forms of FMS-like tyrosine kinase 3 (FLT3) with potential antineoplastic
activity. Following administration, FLT3 tyrosine kinase inhibitor TTT-3002 binds
to and inhibits ligand-dependent dimerization and autophosphorylation of mutant forms
of FLT3 with constitutively activating mutations, including FLT3 internal tandem duplication
(FLT3/ITD) and the activating point mutation D835Y. Prevention of autophosphorylation
inhibits uncontrolled FLT3 signaling and may result in the inhibition of proliferation
in tumor cells expressing constitutively active mutant forms of FLT3. The ability
of TTT-3002 to inhibit FLT3 proteins with activating point mutations may result in
increased efficacy because the activity of these mutants are resistant to other FLT3
kinase inhibitors. FLT3, a tyrosine kinase receptor, plays a role in the regulation
of hematopoietic progenitor cell proliferation, and in leukemic cell proliferation
and survival. Constitutively activating mutations of FLT3 are the most frequent genetic
alterations in acute myeloid leukemia.;