Table 1.

Clinical trials of metabolic diseases by targeting protein modifications

No.	Drug	Modification	Mechanism	Phase	NCT number
1	Atorvastatin	Prenylation	An HMG-CoA reductase inhibitor; Inhibits the posttranslational prenylation of small guanosine triphosphate binding proteins.	II	NCT02633956
2	Curcumin	Phosphorylation Ubiquitination O-GlcNAcylation	An ACC inhibitor; Phosphorylates and inactivates ACC; Inhibits protein ubiquitination; Inhibits O-GlcNAcylation pathway.	IV	NCT01052025
3	MK-4074	Phosphorylation Ubiquitination O-GlcNAcylation	An ACC inhibitor; Phosphorylates and inactivates ACC; Inhibits protein ubiquitination; Inhibits O-GlcNAcylation pathway.	I	NCT01431521
4	PF-05221304	Phosphorylation Ubiquitination O-GlcNAcylation	An ACC inhibitor; Phosphorylates and inactivates ACC; Inhibits protein ubiquitination; Inhibits O-GlcNAcylation pathway.	I II	NCT03248882 NCT03776175
5	Firsocostat	Phosphorylation Ubiquitination O-GlcNAcylation	An ACC inhibitor; Phosphorylates and inactivates ACC; Inhibits protein ubiquitination; Inhibits O-GlcNAcylation pathway.	II	NCT02856555
6	Resveratrol	Acetylation	Decreases PGC-1α acetylation.	I	NCT02704494
7	Selonsertib (GS-4997)	Phosphorylation	An ASK1 inhibitor; Phosphorylates p38/JNK.	II IIb N/A I II II III III	NCT02177786 NCT04026165 NCT02781584 NCT02509624 NCT02466516 NCT03449446 NCT03053063 NCT03053050
8	BGP-15	Phosphorylation	A PARP inhibitor; Phosphorylates Akt and GSK-3, prevents p38/JNK activation.	II	NCT01069965
9	Tropifexor	Acetylation	A FXR agonist; Acetylates FXR; Blocks connection of FXR and the SUMO ligase PIASγ.	II II	NCT02855164 NCT02854605
10	Cilofexor	Acetylation	A FXR agonist, acetylated FXR Blocks connection of FXR and the SUMO ligase PIASγ.	II II II	NCT02854605 NCT03449446 NCT03987074
11	Emricasan	Phosphorylation Nitrosylation Ubiquitination SUMOylation Acetylation	A pan-Caspase inhibitor; Inhibits SUMOylation of the ligand-binding domain.	II II	NCT02686762 NCT03205345
12	Dorzagliatin	SUMOylation Nitrosylation	A GK agonist; Promotes SUMOylation of pancreatic glucokinase.	II	NCT03141073
13	MK-0941	SUMOylation Nitrosylation	A GK agonist; Promotes SUMOylation of pancreatic glucokinase.	III	/
14	AZD1656	SUMOylation Nitrosylation	A GK agonist; Promotes SUMOylation of pancreatic glucokinase.	II II	NCT01152385 NCT01020123
15	Trodusquemine	Phosphorylation Nitrosylation Sumoylation	A PTP1B inhibitor; Inhibits phosphorylation, nitrosylation and SUMOylation at active site Cys215.	I I I I	NCT00509132 NCT00806338 NCT00606112 NCT02524951
16	Sodium phenylbutyrate	Acetylation	A HDAC inhibitor; Inhibits histone deacetylase.	I	NTR7426

HMG-CoA 3-hydroxymethylglutaryl coenzyme A, ACC acetyl-CoA carboxylase, FASN fatty acid synthase, AMPK AMP-activated protein kinase, PGC peroxisome proliferator-activated receptor-gamma coactivator, PARP poly (ADP-ribose) polymerase, ASK1 apoptosis signal-regulating kinase 1, JNK Jun N-terminal kinase, TGF transforming growth factor, FXR farnesoid X receptor, GK glucokinase, PTP1B protein tyrosine phosphatase 1B