Description
Tyrphostins are tyrosine phosphorylation inhibitors that act by inhibiting tyrosine kinases. AG957 is a tyrphostin that targets transforming Bcr-Abl fusion proteins (p185
Bcr-Abl, p210
Bcr-Abl), as well as normal c-Abl (IC
50s = 4.3, 1, and 7.1 μM, respectively, for human proteins). It also inhibits epidermal growth factor receptor (IC
50 = 0.25 μM). As the constitutively-active 210 kDa Bcr-Abl fusion protein commonly occurs in chronic myelogenous leukemia (CML) cells, AG957 is commonly used to study Bcr-Abl signaling in the CML K562 cell line. AG957 is also used to study signaling through c-Abl.
References
[1]. anafi m, gazit a, gilon c, et al. selective interactions of transforming and normal abl proteins with atp, tyrosine-copolymer substrates, and tyrphostins. j biol chem. 1992 mar 5;267(7):4518-23.
[2]. kaur g, gazit a, levitzki a, et al. tyrphostin induced growth inhibition: correlation with effect on p210bcr-abl autokinase activity in k562 chronic myelogenous leukemia. anticancer drugs. 1994 apr;5(2):213-22.
[3]. jamieson l, carpenter l, biden tj, et al. protein kinase ciota activity is necessary for bcr-abl-mediated resistance to drug-induced apoptosis. j biol chem. 1999 feb 12;274(7):3927-30.
[4]. fu p, usatyuk pv, lele a, et al. c-abl mediated tyrosine phosphorylation of paxillin regulates lps-induced endothelial dysfunction and lung injury. am j physiol lung cell mol physiol. 2015 may 15;308(10):l1025-38.
