Table 1.

Inhibitors that control metabolic signaling.

Inhibitor	Chemical Structure	Mode of Regulation	Disease Types	References
Glycolysis inhibitors
2-DG		Competitively inhibits the production of glucose-6-phosphate	Acute lung and kidney injury in mice; COVID-19 and herpes simplex virus infected patients	91-93
3-(3-pyridinyl)-1-(4-pyridinyl)-2-propen-1-one		Binds to PFKFB3 in a dose-dependent manner	Acute lung injury mice model	88
4-Octyl itaconate		Binds to Cys22 of GAPDH	Endotoxaemia mice model	95
Capsaicin		Binds to Cys424 of PKM2	Septic shock mice model; neuropathic pain and amyotrophic lateral sclerosis patients	96
iminostilbene or shikonin		Binds to PKM2 in a dose-dependent manner	Myocardial ischemia-reperfusion injury and non-alcoholic fatty liver disease mice models	97, 99
TEPP-46		Promotes PKM2 tetramer formation	Encephalomyelitis and multiple sclerosis mice models	20
DASA-58		Promotes PKM2 tetramer formation	Hepatic fibrosis mice model	18, 101
D5		Promotes PKM2 tetramer formation	Ulcerative colitis mice model	102
NADPH oxidase inhibitors
Apocynin		Blocks p47phox membrane translocation	Corneal alkali burn mice model; sodium-induced declines in cutaneous microvascular function bronchial asthma patients	104, 105, 148
LDC7559 /NA-11		Binds to the AMP/ADP allosteric activation site	Neutrophil-induced bronchial epithelial damage mice model	28
GKT137831 (Setanaxib)		Direct inhibitor of NOX1 and NOX4	Type 2 diabetes and primary biliary cholangitis patients	Clinical trial No. NCT02010242, NCT03226067
ML090		NOX5 inhibitor	Stroke patients	107
ROS Scavenger
MitoQ		A mitochondria-targeted antioxidant	Tissue hypoxia induced by neurological deficits in mice; improve vascular function Parkinson's disease exercise-induced mitochondrial DNA damage in patients	108-112
Tiron (sodium 4,5-dihydroxybenzene-1,3-disulfonate)		A mitochondria-targeted antioxidant	Airway remodeling and erectile dysfunction in mice	113-115
mito2HOBA (4-(4-aminomethyl)-3-hydroxyphenoxy)butyl)-triphenylphosphonium)		A mitochondria-targeted isolevuglandins scavenger	N/A	116
nicotinamide mononucleotide (NMN) and nicotinamide riboside (NR)		Activate enzymes control biosynthesis of NAD	Aged mice; and prediabetes patients	117, 118
Itaconate derivative
4-Octyl itaconate		Protects against lethality and systemic inflammation induced by LPS	Septic shock mice model	69
cGAS inhibitors
PF-06928215		Binds to the catalytic domain of cGAS	Aged mice and high fat diet-induced cardiac anomalies in mice	81
Compounds 18, S2, and S3		Binds to the catalytic domain of cGAS	N/A	119
RU.521		Binds to residues Arg364 and Tyr421 of cGAS	Subarachnoid hemorrhage-induced brain injury, cerebral venous sinus thrombosis, acute liver injury, rheumatoid arthritis, and postoperative cognitive dysfunction models in mice	120
G108 and G150		Binds to the active site of cGAS	N/A	121
Cu-32, Cu-76, and their analogs		Binds to the dimer interface of human cGAS	N/A	122
hydroxychloroquine sulfate, chloroquine, and quinine		Inhibits cGAS upon dsDNA stimulation of	Antineoplastic effects in mice; rheumatoid arthritis, systemic lupus rythematosus, and SARS-CoV-2 infection in patients	123
X6		Blocks interaction of cGAS to dsDNA	N/A	124
Suramin		Inhibits the enzymatic activity of cGAS	Osteoarthritis, chikungunya virus infection, and diabetic nephropathy in mice	127, 128, Clinical trial No. NCT04496596
Aspirin		Binds to residues Lys384, Lys394, or Lys414 of cGAS	Atherosclerotic cardiovascular disease, diabetes, and periodontitis in mice; patients with atherosclerotic cardiovascular disease	129
STING inhibitor
Nitrofuran derivative C-170, C-171, C-176, C-178, and the indoles derivative H-151		Disrupt assembly of the multimeric STING complexes	N/A	83, 131
SP23		Blocks assembly of the multimeric STING complexes	Mice renal cell carcinoma model	132
Nitro-fatty acids (NO2-FAs)	Not disclosed	Binds to residues Cys88, Cys91, and His16 of STING	Mice myocardial fibrosis model	133
BPK-21 and BPK-25		Binds to residue Cys 91 of STING	N/A	134
Compound 18		Binds to residues Thr263 and Thr267 of STING	N/A	135
Astin C		Binds to the cyclic dinucleotide sites of STING	Colitis and cardiac anomalies in mice	82
Compound 13		A pathway-specific antagonists of cyclic GMP-AMP synthase	N/A	136
AIM2 inhibitors
CRID3		Inhibits formation of ASC complexes	Spinal cord injury in mice	137
Shikonin		Dampens formation of ASC specks and directly inhibit caspase-1 enzymatic activity	Acute liver injury, ovarian cancer, skin diseases, wound healing, and lung cancer in mice	138
J114		Blocks interaction between AIM2 and ASC and inhibit ASC oligomerization	Mice keratitis model	139
Obovatol		Inhibits formation of ASC pyroptosome	Mice Alzheimer's disease, colorectal cancer, bone disorders, and hepatocellular carcinoma models	140
mTOR inhibitor
Rapamycin		Inhibits PI3K-Akt signaling, AMPK and mTOR activity	Glaucoma, lung injury, and aging in mice; tuberous sclerosis complex-associated tumors in patients	141, 149