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MedKoo CAT#: 205834
Description: CWP232204 is a metabolite of CWP232291. CWP232204 is a specific inhibitor of the canonical Wnt signaling pathway, with potential antineoplastic activity. Upon intravenous administration of CWP232291, this agent is converted into its active form CWP232204 and induces the degradation of the downstream effector of the canonical Wnt signaling pathway beta-catenin, thereby preventing beta-catenin-dependent activation of transcription of a wide range of Wnt target genes. This prevents gene expression of many proteins necessary for growth, and induces apoptosis. This may potentially suppress cancer cell growth. The Wnt/beta-catenin signaling pathway regulates cell morphology, motility, and proliferation; aberrant regulation of this pathway leads to neoplastic proliferation. Check for active clinical trials or closed clinical trials using this agent. (NCI Thesaurus). (Last update: 7/23/2015).
MedKoo Cat#: 205834
Synonym: CWP232204; CWP 232204; CWP-232204.
IUPAC/Chemical Name: NONE
CWP232291 promotes degradation of beta-catenin, exhibits potent growth inhibitory activity in several MM cell lines (RPMI-8226, OPM-2, NCI-H929, JJN3, and EJM) with IC50 values of 13 - 73 nM. The inhibitory activity of CWP232291 on Wnt signaling is demonstrated by reporter gene assay and by its effect in down-regulation of Wnt target genes. Using HEK293 cells, CWP232291 treatment dose dependently reduces promoter activity of TOPflash induced by Wnt-3a-Conditioned Media, at a calculated IC50 value of 273 nM. Furthermore, MM cells treated with CWP232291 show downregulated expression of Wnt target genes such as survivin by triggering degradation of beta-catenin. Treatment of these cells with CWP232291 results in activation of caspase-3 and PARP cleavage, indicating induction of apoptosis. To investigate the potential in vivo anti-tumor efficacy of CWP232291, we utilized two MM tumor bearing mice models. Daily or intermittent intravenous (i.v.) administration of CWP232291 led to significant tumor growth inhibition (TGI) in OPM-2 (50 mg/kg, qdx5: regression and 100 mg/kg, biw: 95% TGI) and RPMI-8226 (100 mg/kg, qdx5: regression and 100 mg/kg tiw: 80% TGI) xenograft model with no obvious change in body weight. The anti-tumor efficacies of CWP232291 were dose-dependent and had strong correlations with degradation of beta-catenin in the tumor samples. Potent induction of apoptosis through cleavage of Caspase-3 and PARP and significant decrease of plasma M protein levels in OPM-2 tumor bearing mice were detected as early as 2 and up to 24 hours after single i.v. administration of CWP232291. Taken together, these data clearly demonstrate the impressive anti-tumor profile of CWP232291 with a good therapeutic window and suggest a potential therapeutic application of CWP232291 for the treatment of MM. (source: http://ash.confex.com/ash/2010/webprogram/Paper29280.html).