IWR-1

IWR-1 (IWR-1-endo) is a tankyrase inhibitor targeting Wnt/β-catenin (IC50 = 180 nM). IWR-1 compromises critical steps of the canonical Wnt signaling, namely translocation of β-catenin to the nucleus and subsequent TCF/LEF activation and expression of Wnt/β-catenin downstream targets. IWR-1 promotes β-catenin phosphorylation by promoting stability of Axin-scaffold destruction complexes. IWR-1 can be studied in research for anti-tumor purposes and diseases such as osteosarcoma, colorectal cancer, and psoriasis.

Applications:

• Promotes self-renewal and maintains pluripotency of human embryonic stem cells and mouse Epi-stem cells when used in combination with CHIR99021 (Kim et al.).
• Promotes differentiation of cardiomyocytes from human pluripotent stem cells (PSCs) that have been induced to mesoderm by addition of Activin A and/or BMP4 (Ren et al.; Willems et al.)
• Induces the differentiation of human PSC-derived alveolar epithelial type II (AETII) to AETI cells (Ghaedi et al.).

References and Publications

1. Sara R. Martins-Neves, et al. IWR-1, a tankyrase inhibitor, attenuates Wnt/β-catenin signaling in cancer stem-like cells and inhibits in vivo the growth of a subcutaneous human osteosarcoma xenograft, Cancer Letters, Volume 414, 2018, Pages 1-15.
2. Cell Stem Cell. 2025 Oct 2;32(10):1509-1527.e9.
3. Cell Stem Cell. 2025 Mar 6;32(3):409-425.e8.
4. Adv Funct Mater. 2024 Apr 25;34(17):2309866.
5. Nat Commun. 2024 May 23;15(1):4393.
6. J Adv Res. 2025 Jul 7:S2090-1232(25)00506-5.