Roles of Therapeutic Bioactive Compounds in Hepatocellular Carcinoma

Table 1

Clinical trials and FDA approved molecules that exert inhibitory effect for each signaling pathway.

Compounds/drugs	Chemical structure	Clinical trial/FDA approved	Receptor/target	Description	Inhibitor	References
Vatalanib (PTK787/ZK 222584)		Phase -III	VEGFR1, VEGFR2, VEGFR3, PDGFR-β, c-Kit	Small-molecule tyrosine kinase receptor inhibitor	VEGF signaling pathway	[93]
AE-941 (Neovastat®)	Structure not available	Phase -III	VEGF–VEGFR-binding MMP2, MMP9	Shark-cartilage component	VEGF signaling pathway	[93, 94]
Sorafenib		Phase -III	VEGFR-2, PDGFR-β, FLT3, c-Kit	Small-molecule Raf kinase and tyrosine kinase inhibitor	VEGF signaling pathway	[93]
Trametinib		FDA approved	BRAF	Allosteric, non-ATP competitive small-molecule inhibitors	MAPK pathway	[95, 96]
Binimetinib		FDA approved	BRAF^V600E or BRAF^V600K	Allosteric, non-ATP competitive small-molecule inhibitors	MAPK pathway	[96]
Genistein		Phase I-II	GSK3-β	Inactivate Wnt signaling by upregulating the expression of GSK3-β and E-cadherin	Wnt/β-catenin signalling pathway	[97]
PRI-724		Phase 1	β-Catenin	Blocks the interaction between β-catenin and its transcriptional coactivator CREB-binding protein (CBP)	Wnt/β-catenin signalling pathway	[98, 99]
Idelalisib		USFDA approved	PI3K-δ	Capable of inducing apoptosis and inhibit AKT phosphorylation and downstream effectors	PI3K signaling pathway	[100, 101]
Duvelisib		USFDA approved	PI3K-γ and PI3K-δ	Capable of inducing apoptosis and inhibit AKT phosphorylation and downstream effectors	PI3K signaling pathway	[101, 102]
Erdafitinib		USFDA approved	FGFR1-4	Inhibits tumor cell differentiation, proliferation, angiogenesis	Fibroblast growth factor pathway	[103]
Netarsudil		USFDA approved	ROCK1/2 nonreceptor	Inhibits the enzyme rho kinase	Serine/threonine kinase (AKT) pathway	[104]