IWP-2

IWP-2 is an inhibitor of Wnt processing and secretion with an IC50 of 27 nM. IWP-2 targets the membrane-bound O-acyltransferase porcupine (Porcn) and thus preventing a crucial Wnt ligand palmitoylation. IWP-2 is also an ATP-competitive CK1δ inhibitor with an IC50 of 40 nM for the gatekeeper mutant M82FCK1δ[1][2].

[1]Chen B, et al. Small molecule-mediated disruption of Wnt-dependent signaling in tissue regeneration and cancer. Nat Chem Biol. 2009 Feb;5(2):100-7.|[2]Maiti G, et al. The Wingless homolog Wnt5a stimulates phagocytosis but not bacterial killing. Proc Natl Acad Sci U S A. 2012 Oct 9;109(41):16600-5.|[3]García-Reyes B, et al. Discovery of Inhibitor of Wnt Production 2 (IWP-2) and Related Compounds As Selective ATP-Competitive Inhibitors of Casein Kinase 1 (CK1) δ/ε. J Med Chem. 2018 May 10;61(9):4087-4102.ACS Comb Sci. 2019 Dec 9;21(12):805-816.|Adv Mater. 2021 Oct 10;e2104829.|Autoimmunity. 2023 Dec;56(1):2182741.|Biochem Pharmacol. 2019 Nov;169:113608.|Bioengineering (Basel). 2023 Jun 9, 10(6), 702.|bioRxiv. 2024 Mar 13.|Cell Rep Methods. 2024 May 8:100777.|Clin Sci. 2023 Jan 13;137(1):109-127.|Dev Cell. 2020 Dec 21;55(6):679-694.e11.|Exp Cell Res. 2022 Nov 11;422(1):113416.|Exp Ther Med. 2020 Mar;19(3):1701-1710.|J Appl Polym Sci. 2024 Sep 25.|J Cell Physiol. 2020 Jul;235(7-8):5811-5822.|Microb Pathog. 2024 Sep 21:106960.|Patent. US20180263995A1.|PLoS One. 2024 Jan 5;19(1):e0287206.|SSRN. 2024 Mar 26.|Stem Cell Res Ther. 2024 Oct 8;15(1):350.|Stem Cells Transl Med. 2021 May;10(5):743-755.|Nat Protoc. 2024 Mar 28.