Inhibitor of TNKS, TNKS2
Protein target names: TNKS, TNKS2
Mechanism of action: Inhibitor
In Vitro Validations
DOI Reference: 10.1158/0008-5472.CAN-11-3336
In Cell Validations
In Vivo Data
No in Vivo Validations
SERP ratings and comments
Even though authors have demonstrated that JW55 is a potent inhibitor of the Wnt canonical signalling by facilitating beta-catenin degradation, not enough data was presented on the efficacy of JW55 on TNKS1/2. Selectivity, target validation and IC50 data are severely lacking. The cited literature seems to be primarily focused on investigating the effect of JW55 on Wnt canonical signalling pathways rather than developing it as a probe for TNKS1/2.
Weak probe with iffy biochemical support. Stay away!
More potent analogs of JW55 are already available (doi:10.1016/j.bmcl.2015.12.018). Citation of this paper regarding moderate potency: "In vitro inhibition, as measured by biochemical assay complemented the ST-Luc/ren assay, showed moderate potency of 1 (JW55) towards tankyrases (TNKS1 IC50 1.80 µM, TNKS2 IC50 2.01 µM, ST-Luc/Ren IC50 1.23 µM)...". It should be noted that the authors express doubt in the discussion of the key reference regarding to mechanism of action (doi: 10.1016/j.bmcl.2015.10.079): "However, despite the substantial increased specifity of JW55 to the PARP domain of TNKS1/2 when compared with XAV939, we cannot rule out that JW55 may affect additional mechanisms that contribute to the observed effects in colon cancer lines...".