{"entity":{"id":"tk216","kind":"drug","name":"TK216","aka":["TK-216"],"tldr":"TK216 was an attempt to hit the fusion protein that causes Ewing sarcoma directly, something long thought impossible for a transcription factor. In early trials with vincristine it produced a few responses but not enough to carry the drug forward.","summary":"TK216 was Oncternal Therapeutics' first-in-class small molecule aimed at EWS-FLI1, the fusion transcription factor present in about 85 percent of Ewing sarcomas. It was given as a continuous intravenous infusion, alone and with vincristine, in a phase 1/2 trial in relapsed or refractory Ewing sarcoma. A minority of heavily pretreated patients had objective responses, including some complete responses, but the response rate did not meet the threshold for a registrational study and the sponsor did not continue development.\n\nThe Ewing sarcoma page names it with IGF-1R antibodies and PARP inhibitors among the targeted approaches that have not yet succeeded, while lurbinectedin and combinations remain in trials.","status":"phase-2","asOf":"2026-09-17","links":[],"tags":["subtype-drugs-wave"],"related":["vincristine","lurbinectedin"],"cancers":["ewing-sarcoma"],"sections":[],"technologies":[],"targets":["ewsr1-fli1"],"drugs":[],"companies":["oncternal-therapeutics"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"code":"TK216","modality":"Small-molecule EWS-FLI1 inhibitor","mechanism":"Designed from the YK-4-279 series to bind the EWS-FLI1 fusion oncoprotein and prevent its interaction with RNA helicase A, disabling the transcription factor that drives Ewing sarcoma; it also disrupts microtubules.","approvals":[],"mechanismSteps":[],"toxicity":[],"access":[],"regulatoryEvents":[]},"route":"/drugs/tk216/","neighbours":{"drug":[{"id":"lurbinectedin","kind":"drug","name":"Lurbinectedin","route":"/drugs/lurbinectedin/"},{"id":"vincristine","kind":"drug","name":"Vincristine","route":"/drugs/vincristine/"}],"cancer":[{"id":"ewing-sarcoma","kind":"cancer","name":"Ewing sarcoma","route":"/cancers/ewing-sarcoma/"}],"target":[{"id":"ewsr1-fli1","kind":"target","name":"EWSR1-FLI1 fusion","route":"/targets/ewsr1-fli1/"}],"company":[{"id":"oncternal-therapeutics","kind":"company","name":"Oncternal Therapeutics","route":"/companies/oncternal-therapeutics/"}]}}