We have established a tankyrase inhibitor (TNKSi) drug development program and have discovered highly potent small-molecule tankyrase inhibitors that block cancer -promoting WNT/β-catenin and YAP signaling activities. Comprehensive evaluation of effect in animal models as well as pharmacokinetics/ ADME testing and safety profiling is ongoing for our preclinical candidate-stage drugs aiming for early-stage clinical testing.
To evaluate the effect and mechanism of action for TNKSi monotherapy and combination therapies in the regulation of signaling pathways in cancer using cell culture and mouse models.
WNT/β-catenin signaling can play a central regulatory role in immune cell homeostasis, development and function as well as in peripheral T cell activation, differentiation and tumor cell -immune cell interplay. The objective is to assess the effect of and mechanism of action behind TNKSi/immune checkpoint inhibitor anti-cancer combination therapy as well as the involvement of the adaptive and innate immune system using isogenic mouse models.
Tse J, O'Keefe R, Rigopolous A, Carli ALE, Waaler J, Krauss S, Ernst M, Buchert M(2023) A Mouse Model for the Rapid and Binomial Assessment of Putative WNT/β-Catenin Signalling Inhibitors Biomedicines, 11(10) DOI 10.3390/biomedicines11102719, PubMed 37893093
Brinch SA, Amundsen-Isaksen E, Espada S, Hammarström C, Aizenshtadt A, Olsen PA, Holmen L, Høyem M, Scholz H, Grødeland G, Sowa ST, Galera-Prat A, Lehtiö L, Meerts IATM, Leenders RGG, Wegert A, Krauss S, Waaler J(2022) The Tankyrase Inhibitor OM-153 Demonstrates Antitumor Efficacy and a Therapeutic Window in Mouse Models Cancer Res Commun, 2(4), 233-245 DOI 10.1158/2767-9764.CRC-22-0027, PubMed 36873622
Lien VT, Kristiansen MK, Pettersen S, Haugen MH, Olberg DE, Waaler J, Klaveness J(2019) Towards dual inhibitors of the MET kinase and WNT signaling pathway; design, synthesis and biological evaluation RSC Adv, 9(63), 37092-37100 DOI 10.1039/c9ra08954c, PubMed 35539091