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Table 1 Small-molecule compounds inhibiting CSC progression through suppressing Wnt signaling pathway

From: Emerging agents that target signaling pathways in cancer stem cells

Name Target Mechanism Type of cancer Phase NCT number (starting time)/publication date Assessment
Wnt974 Wnt Inhibits the proliferation of breast CSCs Breast cancer Phase I NCT01351103(May 10, 2011) Dysgeusia [11]
Niclosamide Wnt/β-catenin Selectively targets ovarian CSCs Ovarian cancer Preclinical July, 2014 Without significant toxicity [12,13,14]
LRP6, β-catenin Decreases ALDH+ population cells Basal-like breast cancer Preclinical April, 2014
Wnt/β-catenin Suppresses CSC populations and self-renewal ability Colorectal cancer Phase II NCT02519582 (August 11, 2015)
ONC201 Wnt/β-catenin Inhibits CSC self-renewal and deregulates CSC markers and CSC-related gene expression Glioblastoma cancer Phase I/II NCT02038699 (January 16, 2014) Well tolerated, Grade III neutropenia, Grade II allergic [15, 16]
Prostate cancer Preclinical August 2, 2017
XAV939 β-catenin Attenuates CSC-mediated chemoresistance Colon cancer Preclinical April, 2016 Induces cardiotoxicity and limited therapeutic window [17]
HNSCC Preclinical October, 2019
TFP Wnt/β-catenin Inhibits lung CSC spheroid formation and suppresses lung CSC marker expression (such as CD44/CD133) Lung cancer Preclinical December 1, 2012 Induces little systemic toxicity, but grade 0–2 neurologic toxicity [18, 19]
Chelerythrine β-catenin Inhibits CSCs invasion, spheroid-forming ability, and the stem marker such as SOX2 NSCLC Preclinical January 6, 2020 Without systemic toxicity [20, 21]
FH535 Wnt/β-catenin Deregulates pancreatic CSC marker CD24 and CD44 expression Pancreatic cancer Preclinical July 26, 2016 Without side effects according to the current studies, still need experiments to prove [22]
Wnt-C59 Wnt Decreases sphere formation of CSCs NPC Preclinical June 10, 2015 Exhibits no apparent toxicity in mice; needs experiments to prove [23]
IWR-1 β-catenin Impairs CSCs self-renewal and hampers the expression of key stem markers, and increases doxorubicin sensitivity Osteosarcoma Preclinical February 1, 2018 Well tolerated in mice, but still needs to be thoroughly studied [24]
IC-2 Wnt Reduces the population of CD44+ (liver CSCs) and the ability of sphere-forming ability HCC Preclinical July, 2017 Not reported, still needs experiments to prove
Wnt Reduces the expression of CSC marker and sphere formation ability CRC Preclinical August, 2017
JIB-04 β-catenin Inhibits the metastasis of colorectal CSCs Colorectal cancer Preclinical April 26, 2018 Without general toxicity in JIB-04-treated mice, but still needs experiments to prove [25]
DTX and SFN β-catenin Inhibits the self-renewal ability of breast CSCs Breast cancer Preclinical July, 2016 DTX has the side effect of neurological toxicity, nausea, diarrhea, and alopecia, but SFN is without significant toxicity [26, 27]
PP β-catenin Inhibits the self-renewal ability of breast CSCs Breast cancer Preclinical March, 2016 PP shows no obvious toxicity in mice. But the poor targeting of it made the dosage large. It would be better to improve dosage form and develop new derivatives [28]
OXT-328 October, 2012 Safety according to the recent researches [28]
AD and Ts Wnt/β-catenin Decreases CSC number and activity, and reduces CSC marker expression (such as SOX2, ALDH1, and NOS2) Lung cancer Preclinical December 3, 2019 AD has hepatoxicity, and TS is without toxic side effects in nude mice [29, 30]