Table 2 The components involved for each type of signaling with available inhibitors and their current state in clinical trials.

Signal path element	Inhibitor	Mode of action	Clinical trial status	Reference
Smo inhibitors	Vismodegib	Keeped the transcription factors GLI1/2 in an inactive state.	Phase I and II trials	[142,143,144]
	sonidegib	Blocked the abnormal activation of the HH signaling pathway.	Phase I and II trials	[145]
	Cyclopamine	Binded to the seven-helix receptor of Smo protein.	Preclinical	[149]
	Inoscavin A	Reduced the expression levels of key proteins in the Hh signaling pathway, such as Shh, Ptch1, Smo and Gli1.	Preclinical	[151]
Gli inhibitors	Garcinone C	Inhibited AKT phosphorylation and induced G0/G1 arrest.	Preclinical	[152]
	GANT61	Its hydrolysate, GANT61-D, binded to a specific region of Gli1 protein.	Preclinical	[155]
	HH78	competitively binded to SMO and suppressed GLI transcriptional activity.	Preclinical	[156]
	ATO	Directly inhibited the transcriptional activity of GLI1 protein and blocked HH/GLI signaling pathway	Phase I, II and III trials	[146]
PI4KB inhibitors	Pipinib	Selective inhibition of PI4KB reduced PI4P levels and prevented HH-mediated ciliary localization of Smo protein.	Preclinical	[154]

Smo inhibitors (e.g., Vismodegib, Sonidegib, Cyclopamine, Inoscavin A), Gli inhibitors (e.g., Garcinone C, GANT61, HH78, ATO), and PI4KB inhibitors (e.g., Pipinib) are among the inhibitors listed in Table 2 that target distinct elements of the Hh signaling pathway. These inhibitors function in various ways. The clinical trial status of these inhibitors, including those undergoing phase I/II clinical trials and those still undergoing pre-clinical research, is also listed in Table 2. These findings offer a scientific foundation for upcoming medication development and clinical care, as well as a valuable resource for comprehending the mechanism of action and potential clinical uses of Hh signaling pathway inhibitors.Hedgehog signaling pathway inhibitor in the clinical trials from Public Chemical Database (https://pubchem.ncbi.nlm.nih.gov/).

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