Table 1.

Molecular targets of liver injury, NAFLD and fibrosis.

Types	Targets	Active agents	Advantages	Clinical trial status or pre-clinical study	Ref.
Insulin-sensitizers	PPAR agonist	Pioglitazone	Decrease in blood glucose level	Phase 4 completed /NCT00994682	Ahn et al.
		Lanifibranor	Reduces hepatic glucogenesis, lipogenesis, and steatosis	Phase 2b/NCT03008070	Sven et al.
	FXR agonist	Obeticholic acid	Regulates the metabolic homeostasis of bile acids	Phase 3 completed/NCT02548351	Younissi et al.
	GLP-1 agonist	Liraglutide	GLP-1 receptor antagonist for NAFLD/NASH prevention/treatment	Phase 2 completed/NCT01237119	Mantovani et al.
	FGFR agonist	Pegbelfermin	Regulates lipid and glucose metabolism	Phase 2 active, not recruiting/NCT03486899	Charles et al.
	SCD1 inhibitor	Aramchol	Decreases the synthesis and increases β oxidation of fatty acids	Phase 2 and 3 completed/NCT02279524	Safadi et al.
	AMPK agonist	PF-06409577	Reduces de novo lipogenesis to slow the development of NAFLD	Evaluated in rodent and primate models	Esquejo et al.
	APOC3 inhibitor	Gemcabene	Reduces hepatic de novo triglyceride and cholesterol synthesis	Phase 2 completed in FPLD adults/NCT03508687	Oniciu et al.
Anti-apoptosis	Pan-caspase inhibitor	Emricasan	Reduce cell death in liver injury due to apoptosis	Phase 2b NASH/NCT02960204	Tsao et al.
	ASK1 inhibitor	Selonsertib	Combination with Simtuzumab for NASH and stage 2–3 fibrosis	Phase 3 terminated/NCT03053050	Loomba et al.
	TNF-α inhibitor	Pentoxifylline	A nonspecific PDE inhibitor upregulates cAMP and reduces TNF-α	Phase 2 completed/NCT00590161	Du et al.
Anti-inflammation	Amine oxidase inhibitor	BI 1,467,335	Good oral bioavailability and nanomolar potency	Phase 2 completed/NCT03166735	Schilter et al.
	CCR2 and CCR5 antagonist	Cenicriviroc	Inhibits macrophage accumulation in the liver and ameliorates fibrosis	Phase 2 terminated/NCT03059446	Anstee et al.
	Adenosine receptor agonist	Namodenoson	Inhibits c-AMP, PKA, PI3K and p-Akt and protects from liver damage	Phase 2 Not yet recruiting/NCT04697810	Fishman et al.
	BRD4 inhibitor	JQ1	Enhanced sensitivity of BRD4 and block of HSC activation	Evaluated in rodent and primate preclinical models	Ding et al.
	Galectin-3 antagonist	GR-MD-02	Reverse liver fibrosis/cirrhosis and reduces portal hypertension	Phase 2 completed/NCT02421094	Chalasani et al.
	PDE3/4 inhibitor	Roflumilast	Normalizes hydroxyproline, TGF-β1 and NF-κB levels	Phase 2 terminated/NCT01703260	Essam et al.
	Anti-LPS antibody	Imm124-E	Exerts an immunomodulatory effect and alleviates target Organ damage and lipid profile	Phase 2 completed/NCT02316717	Mizrahi et al.
Anti-fibrosis	Hedgehog inhibitor	MDB5	Better inhibition of Hedgehog downstream GLI target genes than GDC-0449	Evaluated in rodent models	Kumar et al.
	Angiotensin II receptor blocker	Losartan	Reduces PAI-1 production and improves insulin sensitivity	Phase 2 completed in pediatric NAFLD/NCT03467217 Phase 2 completed/NCT01913470 Phase 3 completed in NASH/NCT01051219	Vos et al.
	TGF-β1 inhibitor	Vactosertib	Inhibits TGF-β1 activation	Evaluated in rodent and primate preclinical models	Kim et al.