TABLE 1.

Clinical trials of some small molecular agents used for liver fibrosis/cirrhosis treatment.

Drug	Targeted cell type	Signaling pathway	Disease condition	Phase	Clinical trial number
Hydronidone	HSCs	IRE1α‐ASK1‐JNK signaling pathway (↑) 73	HBV‐related liver fibrosis	III	NCT05905172
		TGFβ‐Smad signaling pathway (↓) 74
Candesartan	Endothelial cells	Nostrin‐eNOS‐NO signaling pathway (↓) 75	HCV‐related liver fibrosis; Alcoholic liver fibrosis	I, II III	NCT03770936 NCT03770936
Emricasan	Hepatocytes	Improve the phenotype of hepatocytes and their paracrine mechanisms 76	Decompensated cirrhosis	II	NCT03205345
Selonsertib	HSCs	ASK1/MAPK signaling pathway (↓) 77	Decompensated cirrhosis	III	NCT03053063
Cenicriviroc	Macrophages	CCR2‐STAT1/NF‐κB/ERK signaling pathways (↓) 78	Non‐alcoholic Steatohepatitis and liver fibrosis	III	NCT03028740
	Macrophages	Depend on the phosphorylation of Erk to promote the expression of Hif1α 79
Resmetirom	–	STAT3 and NF‐κB signaling pathway (↓) 80	Non‐alcoholic Steatohepatitis and liver fibrosis	III	NCT03900429
Obeticholic acid	HSCs	FXR signaling pathway (↑) 81	Primary biliary cholangitis and liver cirrhosis	IV	NCT02308111
Pirfenidone	HSCs	Target Glutaredoxin‐1 and promote the deglutathionylation of Smad3 (↑) 82 TGF‐β/Smad signaling pathway (↓) 83	Advanced liver fibrosis Advanced liver fibrosis Compensated cirrhosis	II II II	NCT04099407 NCT05542615 NCT06267794
Atorvastatin	HSCs	The expression of NOX1, Rac1‐GTP, and Rac1 (↓); oxidative stress (↓) 84	Liver cirrhosis	IV	NCT04072601
Atorvastatin coenzyme A	–	Non‐canonical Hh signaling pathway (↓) 85	Liver cirrhosis	IV	NCT04072601

Note: “↑” represents the promotion of the signaling pathway and “↓” represents the inhibition of the signaling pathway.

Abbreviations: ASK1, apoptosis signal‐regulating kinase‐1; CCR2, CC chemokine receptor 2; eNOS, endothelial nitric oxide synthase; FXR, farnesoid X receptor; HBV, hepatitis B virus; HCV, hepatitis C virus; Hh, hedgehog; Hif1α, hypoxia‐inducible factor 1alpha; HSCs, hepatic stellate cells; IRE1α, inositol‐requiring enzyme‐1alpha; JNK, c‐Jun N‐terminal kinase; MAPK, mitogen‐activated protein kinase; NO, nitric oxide; NOX1, NADPH oxidase 1; STAT1, signal transducer and activator of transcription 1; STAT3, signal transducer and activator of transcription 3; TGF‐β, transforming growth factor‐beta.

Data sources: PubMed (https://pubmed.ncbi.nlm.nih.gov/) and Clinicaltrial (https://clinicaltrials.gov/).