Table 1 Drugs that target metabolism in macrophages

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]