Table 2 Small-molecule compounds inhibiting CSC progression through suppressing Notch 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 |
|---|---|---|---|---|---|---|
MK-0752 | γ-secretase | Decreases the population of CD44+/CD24− and ALDH+, reduces mammosphere-forming efficiency, and inhibits tumor regeneration in BCSCs | Breast cancer | Phase I | NCT00645333 (March 27, 2008) | Well tolerated, but exists dose-limiting toxicity (DLT) [58] |
PF-03084014 | γ-secretase | Inhibits CSC self-renewal and proliferation, and induces CSCs differentiation | HCC | Preclinical | August, 2017 | Induces gastrointestinal toxicity and exists DLT [59] |
N1ICD, Hes-1, and Hey-1 | Decreases CD44+/CD24− and ALDH+ population | Pancreatic cancer | Phase II | NCT02109445(April 9, 2014) | ||
Notch | Diminishes CD133+/CD44+ and ALDH+ subpopulations and eliminates CSCs | Breast cancer | Phase I | NCT01876251(June 12, 2013) | ||
RO4929097 | γ-secretase | Combined with 5-FU can decrease the proportion of CSC subgroup | INS | Preclinical | February, 2018 | Fatigue is the most common toxicities, but it has DLT [60] |
DAPT | Notch1 | Inhibits the proliferation of LSCs and regulates LSC self-renewal | Leukemia | Preclinical | December, 2006 | Induces low toxicity in cell and mice [61] |
Inhibits the self-renewal ability of ovarian CSCs and the expression of stem markers | Ovarian cancer | Preclinical | June, 2011 | |||
Quinomycin A | Notch ligands | Inhibits pancreatic cancer microsphere formation, the stem marker and the number of CSCs | Pancreatic cancer | Preclinical | January 19, 2016 | Induces gastrointestinal toxicity [62] |