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JW55

Inhibitor of TNKS, TNKS2

Structure

Information

  • TNKS
  • TNKS2
  • Inhibitor

In Vitro Validations

Uniprot ID: O95271
Target Class: Other post-translational modification
Target SubClass: PARP
Potency: IC 50
Potency Value: 1900 nM
Potency Assay: Biochemical PARylation assays
PDB ID for probe-target interaction (3D structure): --
Structure-activity relationship: Yes
Target aliases:
Poly [ADP-ribose] polymerase tankyrase-1, TNKS1, T ...

DOI Reference: 10.1158/0008-5472.CAN-11-3336

In Cell Validations

In Vivo Data

No in Vivo Validations

Off-Target Selectivity Assesments

Potency end-point : IC50 PARP1 >20 uM
Potency assay (off target): Biochemical PARylation assay.
Probe Selectivity in Vitro:
JW55 had no activity against 8 ARTD isoenzymes.
Probe Selectivity in Cell:
In Shh-Light II cells (Gli1-Luc reporter) and in TNFalpha-activated HEK293 cells (NF-kappaB luciferase reporter), JW55 had no effect on reporter expression up to 10 uM. In HEK293 cells, JW55 dose-dependently countered LiCl-induced Wnt signaling, and this activity was overcome by expression of dominant active beta-catenin. In SW480 and HCT-15 cells, JW55 dose-dependently decreased SuperTop-luciferase reporter gene expression and stabilized AXIN2.
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SERP ratings and comments

SERP Ratings

In Cell Rating
In Model Organisms

SERP Comments:

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...".

(last updated: 12 Aug 2016 )

SERP Ratings

In Cell Rating

SERP Comments:

Weak probe with iffy biochemical support. Stay away!

(last updated: 17 Aug 2016 )

SERP Ratings

In Cell Rating

SERP 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.

(last updated: 9 May 2019 )