PDGFR Tyrosine Kinase Inhibitor V

Uses

Ki11502 is a multi-targeted receptor tyrosine kinase (RTK) inhibitor that selectively inhibits the activity of PDGF β/α receptors with IC50 values less than 10 nM. Ki11502 selectively inhibits PDGF β receptor phosphorylation, proliferation, and proteoglycan synthesis in human vascular smooth muscle cells. Ki11502 can induce Apoptosis) and exhibits profound antiproliferative effects on select subsets of leukemia, including those with Imatinib (HY-15463) resistant mutations. Ki11502 is highly suitable for studying the role of PDGF in vascular diseases, particularly the role of proteoglycans in atherosclerosis[1][2].

Definition

ChEBI: Ki11502 is a member of the class of quinolines that acts as a receptor tyrosine kinase inhibitor and apoptosis inducer with potential for use in treatment of leukemia and colorectal cancer. It has a role as an EC 2.7.10.1 (receptor protein-tyrosine kinase) inhibitor, an apoptosis inducer and an antineoplastic agent. It is a member of quinolines, a member of thioureas, an aromatic ether and a member of benzamides.

General Description

A cell-permeable quinolinyl-thiourea compound that acts a potent, ATP-competitive, and reversible inhibitor of PDGFR (IC₅₀ = 4 and 7.6 nM in ligand-induced cellular PDGFR phosphorylation and in in vitro kinase activity, respectively). Inhibits c-kit receptor only at much higher concentrations (IC₅₀ = 434 and 234 nM in receptor phosphorylation and kinase activity, respectively). Shown to potently inhibit neointima formation in a rat carotid artery balloon injury model in vivo (30 mg/kg, p.o.).

Biochem/physiol Actions

Cell permeable: yes

in vivo

IC 50

PDGFRα: <10 nM (IC₅₀); PDGFRβ: <10 nM (IC₅₀); KIT: 86.81 nM (IC₅₀); KIT670I: 427.8 nM (IC₅₀); FLT3: 37.54 nM (IC₅₀); FLT3D835Y: 541.6 nM (IC₅₀); KDR: 210 nM (IC₅₀)

References

[1] Getachew R, et al. Characterisation of Ki11502 as a potent inhibitor of PDGF beta receptor-mediated proteoglycan synthesis in vascular smooth muscle cells. Eur J Pharmacol. 2010;626(2-3):186-192. DOI:10.1016/j.ejphar.2009.09.066
[2] Nishioka C, et al. Ki11502, a novel multitargeted receptor tyrosine kinase inhibitor, induces growth arrest and apoptosis of human leukemia cells in vitro and in vivo. Blood. 2008 May 15;111(10):5086-92. DOI:10.1182/blood-2007-06-098079