Description
MET is a proto-
oncogene which encodes the hepatocyte growth factor receptor c-
Met. It has normal roles in morphogenesis, migration, apoptosis, and angiogenesis. Dysregulation of c-
Met occurs in many types of cancer. SU11274 is a potent, selective, ATP-competitive inhibitor of c-Met (IC
50 = 20 nM). It has much less or no activity against other receptor tyrosine kinases. SU11274 induces apoptosis and cell cycle arrest in transformed Ba/F3 cells and cancer cell lines.
Uses
SU 11274 is a competitive inhibitor of Met kinase activity.
Definition
ChEBI: 1h-indole-5-sulfonamide, n-(3-chlorophenyl)-3-[[3,5-dimethyl-4-[(4-methyl-1-piperazinyl)carbonyl]-1h-pyrrol-2-yl]methylene]-2,3-dihydro-n-methyl-2-oxo-, (3z)- is a sulfonamide.
Biochem/physiol Actions
SU 11274 is a class I c-Met inhibitor that competes with ATP to bind to the activation loop of c-Met.1 Inhibition of c-Met by SU 11274 is effective in improving the clinical outcome in non-small cell lung cancer cell lines.2
References
[1] wang x1, le p, liang c, chan j, kiewlich d, miller t, harris d, sun l, rice a, vasile s, blake ra, howlett ar, patel n, mcmahon g, lipson ke. potent and selective inhibitors of the met [hepatocyte growth factor/scatter factor (hgf/sf) receptor] tyrosine kinase block hgf/sf-induced tumor cell growth and invasion. mol cancer ther. 2003 nov;2(11):1085-92.
[2] leiser d1, pochon b1, blank-liss w1, francica p1, glück aa1, aebersold dm1, zimmer y1, medová m2. targeting of the met receptor tyrosine kinase by small molecule inhibitors leads to met accumulation by impairing the receptor downregulation. febs lett. 2014 mar 3;588(5):653-8.
