TK216:
Potential First-in-Class ETS Family Inhibitor
11
First ETS family inhibitor in clinic
Class discovered by Jeff Toretsky
Exclusive worldwide license from
Georgetown University
Extensive and fresh IP portfolio
ETS family oncogenes increasingly
implicated in cancer
Discovery of ETS* family inhibitors
TK216 Mechanism of Action
Disrupts protein-protein binding between
ETS protein and RNA Helicase A (RHA)
Inhibits abnormal RNA transcription
Inhibits abnormal RNA splicing
Inhibits expression of other oncogenes
Enhances tumor suppressor expression
Apoptotic tumor cell death
TK216-Vincristine Synergy
Toretsky lab screened ETS inhibitors
against 70 chemotherapeutic or targeted
agents
Unique synergy with vinca alkaloid drugs
MOA identified: Disrupted cell division
machinery
microtubule catastrophe
*ETS = E26 Transformation-Specific oncogene family
Active
Heterodimer
RHA -
EWS-FLI1
Inactive Monomers
TK216
Zöllner
2017 Science Signaling 10(499)
Oncternal data
Model depicting the inhibition of the interaction of EWS/FLI1 and RHA
ETS Fusion Proteins
Ewing sarcoma:
EWS
-
FLI1,
EWS
-
ERG.
AML:
ETV6
-
various (20+).
ALL:
ETV6
-
RUNX1.
Prostate cancer:
TMPRSS2
-
ERG (>50%).
Secretory breast cancer:
ETV6
-
NTRK3.
ETS Overexpression
AML:
FLI1, ERG, ETV5, ETS2.
Prostate cancer:
ERG, ETV1, ETV4, ETV6.
Lung cancer:
ETV5, ETV1, FLI1, ETS1.
Breast cancer:
ETV6, ETV4, SPIB,
ETV5.
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