Table 1.

Drugs that target metabolism in macrophages

Drug	Mechanism	References
Glucose metabolism
Insulin	Promoting glycolysis in monocyte-phagocytes to enhance phagocytosis on tumor cells	[124]
β-Glucan	Promoting glycolysis in macrophages and thereby inducing M1-like polarization	[125]
Fucoidan	Inhibiting the oxidation reaction of macrophages, promoting glycolysis, inducing M1 polarization, and playing an anti-tumor effect	[126]
Ibrutinib	Inhibiting glycolysis in monocyte-phagocyte and weakening its phagocytosis on tumor cells	[124]
Lipid metabolism
Simvastatin	Consuming lipids and transforming M2-like macrophages to M1-like	[127]
Rapamycin + Hydroxychloroquine	Disrupting FAO in macrophages to inhibit M2-like polarization	[128]
Perhexiline	Inhibiting oxidative phosphorylation and fatty acid metabolism to promote M1-like polarization	[129]
Metformin	Inhibiting FAO to induce macrophage polarization to M1 phenotype, suppressing anti-inflammatory macrophage infiltration through decreasing COX2 and PGE2	[29, 130]
Indomethacin	Inhibiting COX and PGE2, inducing anti-tumor effect by macrophages	[131]
Isoliquiritigenin	Inhibition of PGE2 production and reduction of M2-like polarization	[132]
Salvia miltiorrhiza Bunge aqueous extract	Inhibiting COX-2, reducing PGE2 production, decreasing tumor-promoting macrophage infiltration, and mediating anti-tumor immune responses	[133]
Fe-5,5′-azosalicylic acid nanoscale coordination polymer nanomedicines	Producing 5-aminosalicylic acid to reduce COX-2 and PGE2 expression, conversely, generating Fe3 + to induce M1-like polarization	[134]
5-Aminolevulinic Acid	Inhibiting COX-2 and PGE2 expressions, suppressing tumor by macrophages	[135]
Lactic acid metabolism
3-Bromopyruvate	Inhibiting tumor-promoting macrophages by decreasing lactate production	[136]
Albiziabioside A + Dichloroacetate acid	Inhibiting lactate accumulation to reduce M2 macrophages and reprogram anti-tumor microenvironment	[137]
Dual PI3Kδ/γ Inhibitor RP6530	Reducing lactate, inducing M1-like polarization and inhibiting tumor progression	[138]
Amino acid metabolism
6-Diazo-5-oxo-l-norleucine	Inhibiting glutamine metabolism, suppressing IDO expression, and inducing pro-inflammatory macrophages	[139]
6-Gingerol	Inhibiting ARG expression, promoting iNOS and NO expression, enhancing M1-like polarization, and exerting anti-tumor effect	[140]
Triptolide	Reducing ARG1 expression and decreasing M2-like polarization	[141]
1,3-Diaryl-pyrazin-6-one-5-carboxamides	Inhibiting IDO level and reducing immunosuppressive macrophage infiltration	[142]
Sulfasalazine	Inhibiting cystine-glutamate exchange (xCT) and thereby inducing M2-like polarization	[143]
Acid–base metabolism
Anti‐V‐ATPase‐V0a2 antibody	Inhibiting proton pump activity to induce M1-like macrophage	[144]
Pantoprazole	Inhibiting proton pump to induce M1-like polarization and activating anti-tumor immunity	[145]
Iron metabolism
Iron oxide nanoparticles	Iron absorbed by macrophages and thereby replenished to promote M1-like polarization	[146]
Iron chelated melanin-like nanoparticles	Iron supplemented by macrophages to induce M1-like polarization	[147]
Intracellular iron chelator (TC3-S)2	Transforming macrophage to iron-absorbing M1-like phenotype to play anti-tumor effects	[148]