TK216 is a potent E26 transformation specific (ETS) inhibitor[1]. TK216 directly binds EWS-FLI1 and inhibits EWS-FLI1 protein interactions. TK216 blocks the binding between EWS-FLI1 and RNA helicase A. TK216 has anticancer activity[2].
TK216 (500 nM; for 24-72 hours) induces apoptosis in DLBCL cell lines[1]. TK216 (0.03, 0.06, 0.125, 0.25, 0.5 μM) results in a dose-dependent inhibition of proliferation in Ewing Sarcoma A4573 cell line[1]. TK216 (0.1, 0.3, 1 μM) induces apoptosis in DLBCL cell lines, with the amount of cleaved-Caspase 3 normalized to b-actin and presented as fold over control[1]. TK216 has IC50s of 0.363 μM and 0.152 μM for HL-60 AML cell line and TMD-8 DLBCL cell line[1]. TK216 inhibits EWS-FLI1 (Ewing sarcoma breakpoint region 1/Friend leukemia virus integration 1 fusion protein) protein interactions, leading to a decrease in transcription and proliferation[1]. Apoptosis Analysis[1] Cell Line: DLBCL cell lines
TK216 (po; 100 mg/kg; twice daily for 13 days) results in tumor growth inhibition of the TMD-8 xenograft model[1]. Animal Model: NOD-Scid mice subcutaneously inoculated with TMD8 cells[1]
[1]. Spriano F, et al. The ETS Inhibitors YK-4-279 and TK-216 Are Novel Antilymphoma Agents. Clin Cancer Res. 2019 Aug 15;25(16):5167-5176. [2]. Brian Lannutti, et al. Uses of indolinone compounds. US10159660B2.