TK216

TK216 directly binds EWS-FLI1 and inhibits EWS-FLI1 protein interactions, leading to a decrease in transcription and proliferation. TK216 blocks the binding between EWS-FLI1 and RNA helicase A. TK216 is active in oncogenesis and inhibits apoptosis[1].

Signaling Pathways >> Apoptosis >> Apoptosis

Research Areas >> Cancer

EWS-FLI1 protein[1]

TK-216 (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]. TK-216 has IC50s of 0.363 μM and 0.152 μM for HL-60 AML cell line and TMD-8 DLBCL cell line[1]. Apoptosis Analysis[1] Cell Line: DLBCL cell lines Concentration: 500 nM Incubation Time: For 24, 48 or 72 hours Result: Induced apoptosis in DLBCL cell lines.

TK-216 (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] Dosage: 100 mg/kg Administration: Po; twice daily for 13 days Result: Resulted in tumor growth inhibition.

[1]. Brian Lannutti, et al. Uses of indolinone compounds. US10159660B2.