Table 1.

Small-molecule inhibitors targeting the DNL pathway

Drug/small molecule	Target gene	Current status	Disease	Reference(s) or clinical trial no.
Betulin	SREBP1	Preclinical	Hepatocellular carcinoma	Li et al 201747, Yin et al 201988
Curcumin	SREBP1	Preclinical	Hepatocellular carcinoma	You et al 201890
Fatostatin	SREBP1	Preclinical	Hepatocellular carcinoma	Yu et al 202045
Hydroxycitrate	ACLY	Preclinical	Glioblastomas, breast cancer	Beckner et al 2010115, Ismail et al 2020116
ETC-1002	ACLY	Phase 3 clinical trial	Cardiovascular diseases	NCT02993406 117
BMS-303141	ACLY	Preclinical	Hepatocellular carcinoma	Zheng et al 202152
TOFA	ACAC	Preclinical	Hepatocellular carcinoma	Calvisi et al 201120
ND-654	ACAC	Preclinical	Hepatocellular carcinoma	Lally et al 201958
NDI-010976	ACAC	Phase 1 clinical trial	Overweight and/or obesity	NCT02876796 118
C75	FASN	Preclinical	Hepatocellular carcinoma	Gao et al 200663
Orlistat	FASN	FDA approved	Obesity	Guri et al 201766, Zhang et al 202067
Fenofibrate	FASN	FDA approved	Hypercholesterolemia	You et al 2019100
TVB-2640	FASN	Phase 1 clinical trial	Metabolic syndrome	NCT02948569 119
A939572	SCD	Preclinical	Hepatocellular carcinoma	Ma et al 201772
SSI-4	SCD	Preclinical	Hepatocellular carcinoma	Ma et al 201772
CAY10566	SCD	Preclinical	Hepatocellular carcinoma	Huang et al 2015102
MK8245	SCD	Phase 1 clinical trial	Type 2 diabetes	NCT00790556 120

Abbreviation: FDA, Food and Drug Administration.