Sorafenib targets the same molecules as IGF1R inhibitors, reduces IGF1R expression, counteracts IGF-1 binding, and inhibits the in vitro kinase activity of recombinant human IGF1R. (A) CLL B cells were treated with 10 µM sorafenib and immunoblotted for the expression of pPI3K, PI3K, pAkt, Akt, pErk, Erk, pSrc, CXCR4, and Mcl1. A representative example from 8 independent experiments is shown. (B) CLL B cells were treated with 10 µM sorafenib or 15 µM AG1024 and immunoblotted for the expression of pIGF1R, IGF1R, pIRS1, Mcl1, and pCXCR4. A representative example from 10 independent experiments is shown. (C) CLL B cells were treated with a single dose of 10 µM sorafenib or 15 µM AG1024 for 24 hours, and IR expression was determined by flow cytometry (n = 10). (D) CLL B cells were treated with a single dose of 10 µM sorafenib or 15 µM AG1024 for 24 hours, and IGF1R expression was determined by flow cytometry (n = 10). (E) CLL B cells treated with DMSO, sorafenib, linsitinib, AG1024, or PPP were treated with biotinylated IGF-1, and binding of IGF-1 to CLL cells was determined by flow cytometry (n = 3). (F) Sorafenib inhibits the in vitro kinase activity of recombinant human IGF1R. Two IGF1R inhibitors (AG1024 and linsitinib) were used as a positive control. In this assay, the IGF1R activity is measured by luminescence-based detection of adenosine dipsosphate produced during the kinase reaction (n = 3).