Table 1.

Modulators of Hippo signaling pathway

Action mechanism	Compound/molecule	Target	Effect	Development stage	Ref.
Interaction with Hippo’s core complex	C19	MST/LATS	Phosphorylation of MST/LATS	In vivo: inhibition of tumor growth by 90%	54
Direct target YAP/TAZ or its complexes	Verteporfin	YAP-TEAD	Inhibition of the YAP-TEAD interaction	In vitro: inhibition of YAP1 expression and sensitizes cells to cytotoxic drugs In vivo: inhibition of tumor growth in Nf2-depleted mouse model of liver cancer Clinical trial: phase III for the treatment of multiple basal cell carcinoma (NCT00049959)	35, 60
	VGLL4-mimicking peptide	TEAD	Competition with YAP for TEAD binding	In vitro and in vivo: inhibition of tumor growth	56
Targeting upstream regulators	Adrenaline, glucagon, dihydrexidine	GPCRs GαS	Agonists of GαS. Increase YAP phoshorylation	In vitro	42
	Dobutamin	GPC-β- adrenergic receptor	Inhibition of YAP nuclear location	In vitro	57
	Cytochalasin D, latrunculin A and B, blebbistain	F-actin	Destabilizers of F- actin. Inhibition of YAP nuclear localization	In vitro	58
	Botulinum toxin C3, Y27632	Rho	Rho inhibition. Inhibition of YAP/TAZ nuclear location	In vitro	59
	Simvastatin	Rho GTPases	Inhibition of the SREBP/mevalonate cascade needed for RhoGTPase activity	In vitro: inhibition of TAZ and dowregulation of TAZ, YAP, and CTGF transcripts Clinical trials: ongoing in several cancer types (Clinicaltrials.gov).	20, 59
	Dasatinib	YES1	Inhibition of YES1 needed for the YAP-β-catenin complex	Clinical trials: ongoing in several cancer types (Clinicaltrials.gov)	55

Abbreviations: VGLL4, vestigial-like family member 4; YES1, Yamaguchi sarcoma viral oncogene homolog 1.