Table 1.

Current Advances and main clinical trials in metabolism targeting for gliomas therapy.

Drugs or Therapeutics	Trial Phase	Target	Mechanisms	Gliomas type	References or Clinical Trial Identifier*
IDH 305	Phase II	Mutant IDH1	inhibitor of the mutant IDH 1 enzyme	Low Grade Glioma	NCT02987010 NCT02977689
IDH 305	Phase I	Mutant IDH1	mutant IDH small molecule inhibitor	Gliomas withIDH1R132 Mutations	NCT02381886
AG-221	Phase I/II	Mutant IDH2	inhibitor of the mutant IDH2 enzyme	Glioma, mutant IDH2	NCT02273739
AG-120	Phase II	Mutant IDH1	–	Glioma with an IDH1 mutation	NCT02073994
AG-881	Phase III	Mutant IDH1 or IDH2	Inhibitor of Mutant IDH1 and 2	Grade 2 Glioma	NCT04164901
AG-120 and AG-881	Phase I	Mutant IDH 1	Suppression of 2-HG	LGG	NCT03343197
FT-2102	Phase I/II	Mutant IDH 1	IDH1m Inhibitor	LGG, GBM	NCT03684811
BAY1436032	Phase I	Mutant IDH 1	IDH-R132X-inhibitor	Anaplastic glioma, GBM	NCT02746081
Metformin	Early Phase I	AMPK/Mitochondrial complex I	Metformin blocks oxidative phosphorylation in mitochondria	GBM	NCT03151772
	Phase II			GBM	NCT02780024
	Phase I/II			IDH1/2 Gliomas	NCT02496741
	Phase I			GBM	NCT01430351
CB-839	Phase I b	Glutaminase (GLS)	Chemical inhibitor	Diffuse Astrocytoma, IDH-Mutant	NCT03528642
TVB-2640	Phase II	Fatty-acid synthase (FASN)	VB-2640 inhibits the β-ketoacyl reductase (KR) enzymatic activity of the FASN	High Grade Astrocytoma	NCT03032484
PEG-BCT-100	Phase I/II	Arginine	Depletion of circulating arginine	High Grade Gliomas	NCT03455140
Methotrexate	Phase II	Dihydrofolate reductase (DHFR)	Inhibition of folate metabolism and nucleotide synthesis	Glioblastoma multiforme	NCT00082797
Dichloroacetate (DCA)	Phase II	Mitochondrial PDHK	DCA switches metabolism from the cytoplasmic glycolysis to the mitochondrial glucose oxidation	Glioblastoma multiforme	NCT00540176
Ubidecarenone BPM31510	Phase I	Redox toxicity elevation in mitochondrial O2− species	BPM31510 works by correcting cancer cell metabolism,	Glioblastoma multiforme	NCI-2016-01973
ONC201	Phase II	Caseinolytic protease P (ClpP)	ONC201 acts as a ClpP which regulates oxidative phosphorylation	Adults With EGFR-low Glioblastoma	NCT04629209
	Phase I		Targets OXPHOS and suppresses mitochondrial respiration	Pediatric H3 K27M Gliomas	NCT03416530
	Phase II		-	Recurrent H3 K27M-mutant Glioma	NCT03295396
Perifosine KRX-0401	Phase II	AKT/PI3K	inhibitor of Akt and PI3K, modulates phospholipid metabolism	Malignant Gliomas	NCT00590954
Atorvastatin	Phase II	HMG-CoA reductase	Inhibition of cholesterol biosynthesis	Glioblastoma	NCT02029573
2-DG	Phase I/II	Glycolytic enzyme	Glucose analog	Malignant Gliomas	(125)