TK216

• CAT Number: I017630
• CAS Number: 1903783-48-1
• Molecular Formula: C19H15Cl2NO3
• Molecular Weight: 376.23
• Purity: ≥95%
• Synonyms: 4,7-dichloro-3-[2-(4-cyclopropylphenyl)-2-oxoethyl]-3-hydroxy-1H-indol-2-one
• InChI: InChI=1S/C19H15Cl2NO3/c20-13-7-8-14(21)17-16(13)19(25,18(24)22-17)9-15(23)12-5-3-11(4-6-12)10-1-2-10/h3-8,10,25H,1-2,9H2,(H,22,24)
• InChIKey: ZWHNLSHDLKIXOG-UHFFFAOYSA-N
• SMILES: C1CC1C2=CC=C(C=C2)C(=O)CC3(C4=C(C=CC(=C4NC3=O)Cl)Cl)O

TK216 is an orally active and 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].
TK216 (po; 100 mg/kg; twice daily for 13 days) results in tumor growth inhibition of the TMD-8 xenograft model[1].

Reference

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