Uses
AZ 6102 is a a potent TNKS1/2 inhibitor that has 100-fold selectivity against other poly(ADP-ribose) polymerase (PARP) family enzymes.
Biological Activity
az6102 is a tnks1/2 inhibitor.inhibition of the poly(adp-ribose) polymerase (parp) catalytic domain of the tankyrases (tnks1 and tnks2) is reported to inhibit the wnt pathway by increasing stabilization of axin. the canonical wnt pathway plays a critical role in adult tissue homeostasis, embryonic development, as well as cancer.
in vitro
az6102 was identified as a potent tnks1/2 inhibitor with 100-fold selectivity against other parp family enzymes including parps 1, 2, and 6. in addition, az6102 showed a 5 nm ic50 against wnt pathway in dld-1 cells [1].
in vivo
in animal study, az6102 was intravenously dosed to nude mice at 25 mg/kg, and the results showed that az6102 had a clearance of 24 ml/min·kg and a half-life of 4 h. the bioavailability of az6102 in mouse and rat was only moderate at 12% and 18%, respectively. in addition, az6102 was used as an intravenous probe compound to evaluate the in vivo effects of tnks1/2 inhibition on normal tissue and tumor xenografts, however, the results of such experiments have not be released so far [1].
IC 50
1 and 3 nm for tnks2 and tnks1, respectively
References
[1] j. w. johannes, l. almeida, b. barlaam,et al.pyrimidinone nicotinamide mimetics as selective tankyrase and wnt pathways inhibitors suitable for in vivopharmacology. acs med. chem. lett. 6, 254-259 (2015).
