Table 5.

Metabolism-targeted drugs

Strategy	Agent	Experiment status	Application	Cancer biological behavior	Clinical trial/Ref.
GLUTs inhibitor	Silybin	Phase II; In vivo mouse model	Prostate cancer	Suppressed cancer growth	NCT00487721 [271]
	Rapaglutin A	In vivo mouse model; in vitro human cell culture	Breast cancer	Suppressed cancer growth	[272]
HK II inhibitor	Metformin	Phase II	Breast cancer	Inhibited cancer cell proliferation	NCT01266486 [273]
	2-deoxyglucose	Phase I/II	Prostate cancer	Inhibited cancer growth	NCT00633087 [274]
	3-Bromopyruvate	In vitro human cell culture	Liver cancer	Inhibited cancer growth	[275]
CAV-1 inhibitor	Methyl-β-cyclodextrin	In vitro human cell culture	Colorectal cancer	Increased the BITC-induced anti-cancer effect	276
MCT-1 inhibitor	AZD3965	Phase I	Lymphoma	Inhibited cancer growth	NCT01791595 [277]
PDK inhibitor	Dichloroacetate	Phase I; In vitro human cell culture	Advanced solid tumor	Reduced tumor growth and enhanced Adriamycin cytotoxicity	NCT00566410 [278, 279]
	Hordenine	In vitro human cell culture	Lung cancer	Decreased cancer cell proliferation	[280]
IDH inhibitor	Ivosidenib (AG-120)	Phase I	Brain cancer	Inhibited tumorigenesis	NCT02073994 [281]
	Ivosidenib (AG-120)	Phase III	Cholangiocarcinoma	Reduced tumor growth	NCT02989857 [282]
	Enasidenib	Phase I/II	Leukemia	Inhibited cancer growth	NCT01915498 [283, 284]
	Olutasidenib (FT-2102)	Phase I/II	AML	Suppressed tumor growth	NCT02719574 [285, 286]
	Vorasidenib (AG-881)	Phase I	Glioma	Acquired complete remission	NCT02481154 [287]
HIF-1α inhibition	Apigenin	Phase I	Ovarian, prostate and breast cancer	Downregulated tumor angiogenesis	NCT03526081 NCT03139227 [288–292]
	Semaxanib  (SU5416)	Phase II	Metastatic melanoma	Reduced tumor metastasis	NCT00017316 [293]
	2-Methoxyestradiol	Phase I; Phase II	Prostate, breast, brain, head and neck cancer and liver cancer	Inhibited tumor growth and angiogenesis	NCT00030095; NCT00592579 [294–296]
	PX-478	Phase I	Solid tumors and Lymphoma	Enhanced radiosensitivity and suppressed tumor growth	NCT00522652 [297–299]
	BAY 87-2243	Phase I	Neoplasms	Impaired OXPHOS and reduced cancers growth	NCT01297530 [300–302]
OXPHOS inhibition	Lonidamine	Phase II; In vivo mouse model	Glioma	Limited tumor growth	[303, 304]
G6PD inhibitor	Dehydroepiandrosterone	Phase I	Breast cancer	Increased the number of monocytes  and NK cells	NCT00972023 [305]
	Polydatin	In vitro human cell culture	Breast cancer	Increased cancer cell autophagy and lapatinib effect on breast cancer cells	[306]
GSK-3 inhibitor	Lithium chloride	In vivo mouse model; in vitro human cell culture	Pancreatic and breast cancers	Enhanced autophagy and apoptosis in cancer cells and reduced cancer growth	[307]
PGAM1 inhibitor	HKB99	In vivo mouse model	NSCLC	Suppressed tumor growth and metastasis	[308]
	PGMI-004A	In vivo mouse model	NSCLC	Attenuated cell proliferation and tumor growth	[309]
ACSLs inhibition	Triacsin C	In vitro human cell culture	Colon and breast cancers	Decreased cell proliferation and chemotherapy resistance	[310, 311]
ACAT-1	Avasimibe	In vitro human cell culture	Ovarian cancer	Enhanced chemosensitivity to cisplatin treatment	[312]
FASN inhibitor	C75	FDA approved	NSCLC	Reduced tumor growth	[313, 314]
	TVB-2640	Phase II	NSCLC, ovarian, and breast cancer	Inhibited cancer growth	NCT02223247 [315]
	Cerulenin	In vitro human cell culture	Lung cancers	Blocked cancer cell proliferation	[316]
HMGCR inhibitor	Fluvastatin	In vivo mouse model	NSCLC	Inhibited cancer growth	[317]
GLS inhibitor	Telaglenastat (CB-839)	In vivo mouse model	Melanoma	Improvement in tumor growth inhibition with anti-PD1 and anti-CTLA4 antibodies	[318]
	Withangulatin A derivative 7	In vivo mouse model	Breast cancer	Inhibited cancer growth	[319]

GLUT glucose transporter; HK II hexokinase II; CAV-1 caveolin-1; BITC benzyl isothiocyanate; MCT-1 monocarboxylate transporter 1; PDK1 pyruvate dehydrogenase kinase 1; IDH isocitrate dehydrogenase; HIF-1 hypoxia-inducible factor-1; OXPHOS oxidative phosphorylation; G6PD glucose-6-phosphate dehydrogenase; GSK-3 glycogen synthase kinase; PGAM phosphoglycerate mutase; NSCLC non-small cell lung cancer; ACSL acyl CoA synthetase; FASN fatty acid synthase; HMGCR 3-hydroxy-3-methylglutaryl-CoA reductase; and GLS1 glutaminase 1