IWR-1-endo

IWR-1 endo (1127442-82-3) is a potent inhibitor of Wnt signaling (IC50=180 nM).1Inhibits zebrafish tailfin regeneration (0.5 mM).2Acts via inhibition of tankyrase and attenuates Wnt/β-catenin signaling in cancer stem-like cells.3Promotes self-renewal and maintains pluripotency of human embryonic stem cells.4Promotes differentiation of pluripotent stem cells into cardiomyocytes.5

IWR-1-endo act as inhibitors of Wnt response. It appear that IWR compounds induce stabilization of Axin proteins via a direct interaction, which is a part of the b-catenin destruction complex (consists of Apc, Axin, Ck1 and Gsk3b). Such compounds may be used in the treatment of Wnt protein signaling-related diseases and conditions such as cancer, degenerative diseases, type II diabetes and osteopetrosi s.

IWR-3 act as inhibitors of Wnt response. It appear that IWR compounds induce stabilization of Axin proteins via a direct interaction, which is a part of the b-catenin destruction complex (consists of Apc, Axin, Ck1 and Gsk3b).Such compounds may be used in the treatment of Wnt protein signaling-related diseases and conditions such as cancer, degenerative diseases, type II diabetes and osteopetrosis.

ChEBI: IWR-1-endo is a dicarboximide having an endo bridged phthalimide structure, substituted at nitrogen by a 4-(quinolin-8-ylcarbamoyl)benzoyl group. It has a role as an axin stabilizer and a Wnt signalling inhibitor. It is a dicarboximide, a bridged compound, a member of quinolines and a member of benzamides.

A cell-permeable p-imidobenzamidoquinoline, endo-diastereomer that is shown to inhibit the activity of TNKS1/PARP5a and TNKS2/PARP5b in in vitro auto-PARsylation assays (IC₅₀ = 131 and 56 nM, respectively) and effectively suppress Wnt-stimulated transcription activity in L-Wnt-STF-based reporter assays (IC₅₀ = 180 nM), while exhibiting little activity against PARP1 or PARP2 (IC₅₀ >18.75 μM). Although both IWR-1-endo and XAV939 (Tankyrase1/2 Inhibitor; >Cat. No. 575545) act as reversible Wnt pathway inhibitors and exhibit similar pharmacological effects both in vitro and in vivo, IWR-1-endo exerts its effect via interaction with Axin, while XAV939 binds TNKS directly.

Cell permeable: yes

Store at RT

[1] BAOZHI CHEN. Small molecule–mediated disruption of Wnt-dependent signaling in tissue regeneration and cancer[J]. Nature chemical biology, 2009, 5 2: 100-107. DOI:10.1038/nchembio.137
[2] JIANMING LU . Structure–activity relationship studies of small-molecule inhibitors of Wnt response[J]. Bioorganic & Medicinal Chemistry Letters, 2009, 19 14: Pages 3825-3827. DOI:10.1016/j.bmcl.2009.04.040
[3] SARA R. MARTINS-NEVES . 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[J]. Cancer letters, 2018, 414: Pages 1-15. DOI:10.1016/j.canlet.2017.11.004
[4] HOON KIM. Modulation of β-catenin function maintains mouse epiblast stem cell and human embryonic stem cell self-renewal.[J]. Nature Communications, 2013: 2403. DOI:10.1038/ncomms3403
[5] YONGMING REN . Small molecule Wnt inhibitors enhance the efficiency of BMP-4-directed cardiac differentiation of human pluripotent stem cells[J]. Journal of molecular and cellular cardiology, 2011, 51 3: Pages 280-287. DOI:10.1016/j.yjmcc.2011.04.012