IWR-1 (GMP)

IWR-1 (IWR-1-endo) (GMP) is the IWR-1 (HY-12238) produced by using GMP guidelines. GMP small molecules work appropriately as an auxiliary reagent for cell therapy manufacture. 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-scaffolded destruction complexes. IWR-1 can be studied in research for anti-tumor purposes, and diseases such as osteosarcoma, colorectal cancer and psoriasis^[1][2][4]. In Vitro:IWR-1 (GMP) is cytotoxic for osteosarcoma cancer stem-like cells (CSCs)^[1].
IWR-1 (GMP) suppresses cell migration, invasion, and matrix metalloproteinase activities of colorectal cancer cell lines^[2].
IWR-1 (GMP) (2.5-10 μM, 48-96 h) is effective in reducing spheres’ viability in a concentration- and time- dependent manner in parental and spheres from MG-63 and MNNG-HOS cell lines^[1].
IWR-1 (GMP) (10 μM, 96 h) increases the number of TUNEL-positive cells, reaching 4.65- and 15.83-fold differences relative to control at 96 h and promoted the activation of caspases 3/7 reaching 2.15- and 1.27-fold in MG-63 and MNNG-HOS spheres^[1].
IWR-1 (GMP) (10 μM, 48 h) induces a cell cycle arrest in the G2/M phase in spheres derived from MG-63 and MNNG-HOS cell lines and increases the percentage of cells in the S phase slightly^[1].
IWR-1 (GMP) (10 μM, 48 h) inhibits secondary sphere-forming efficacy by approximately 53% and 55% of the first-generation 7-day old spheres in MG-6t4 and MNNG-HOS cells^[1].
IWR-1 (GMP) (5-50 μM, 24-48 h) decreases the proliferation of HCT116 cells in a dose- and time-dependent manner^[2].
IWR-1 (GMP) (5-50 μM, 24-48 h) inhibits TNF-α-stimulated migration in HCT116 and HT29 cells^[2]. In Vivo:IWR-1 (5 mg/kg, intratumorally, each 2 d for 12 d) induces a marked inhibition of tumor growth in osteosarcoma mouse model^[1].
IWR-1 (GMP) (10 mg/kg, s.c., on days 1, 3, 5) ameliorates IL-36γ (2 μg/mouse on days 1, 3, 5)-mediated exacerbation of psoriatic skin lesions in an Imiquimod (IMQ) (HY-B0180)-induced psoriasis-like mice model^[3].