Table 2.

Potential targets and promising agents against glioblastoma metabolism.

Potential Targets	Therapeutic approaches	Study type	Mechanism of action	References
OXPHOS Proteins (complex V)	Gboxin	In vitro and in vivo study	inhibits the activity of F0F1 ATP synthase and thus disrupt cell metabolism	(133)
(MCT1)	AR-C117977 And others	In vitro study	Intracellular acidification and induction of cell death	(134)
LPCAT1	LPCAT1-shRNA	In vivo study	Suppression of EGFR signaling and alteration of membrane lipid remodeling	(135)
PHGDH	inhibition of PHGDH with CBR-5884	In vitro study	Alteration of Serine metabolism	(136)
SOAT1	shRNA mediated LPCAT1 knockdown	In vivo study	Block SREBP-1-mediated lipogenesis	(110)
(ACAT-1)	Inhibition by Avasimibe	In vitro and in vivo study	Decrease cholesteryl ester storage in lipid droplets and increase intracellular free cholesterol balances	(137)
Glycolytic enzymes	3-bromopyruvate (3BP) (An antiglycolytic agent)	In vivo study	3BP induces alterations in proteins involved in aerobic glycolysis and carbohydrate metabolism.	(138)
HK2	ketoconazole and posaconazole (HK2 inhibitors)	In vitro and in vivo study	reduce tumor growth likely via blocking HK2 and affecting tumor metabolism	(139)
HK2 and miR-218	shRNA mediated HK2 silencing/ miR-218 overexpressing	In vitro and in vivo study	miR-218 overexpression downregulates HK2, inducing thereby glycolytic metabolism alteration and cell death.	(140)
LXR	Synthetic LXR agonist (LXR-623)	In vitro and in vivo study	LXR-623 kills GBM cells by reducing cellular cholesterol through activation of LXRβ.	(141)
ACBP	shRNA mediated ACBP knockdown	In vivo study	Reduction of ACBP expression decreases Fatty acid oxidation and hinder GBM cell proliferation.	(114)
SREBP-1, FAS and FDFT1	Phytol (PHY) and retinol (RET)	In vitro study	PHY and RET modulates cholesterol and fatty acid biosynthetic pathways.	(142)
Cholesterol metabolism (SREBP-1, LXR-α, HMG-CR and LDLR…)	27-Hydroxycholesterol (27-OHC)	In vitro study	27-OHC inhibits cholesterol synthesis and promote its transport.	(143)
miR-448–HIF-1α axis	HIF-1α signaling	In vitro study	miR-448 negatively regulates HIF-1 α signaling	(144)
PFK1 and PDK1	Gene Knockdown	In vivo study	Inhibitions of glycolysis and alteration of cellular metabolism	(145)
Glucose analogs	2DG, a glucose analog and glycolytic inhibitor	In vitro study	In combination with metformin Inhibits Proliferation and Cellular Energy Metabolism and induces ER stress in	(146, 147)
Energy Depletion	Dual MR via ONC201/TIC10 and 2-Deoxyglucose	In vitro study	Targeting of OXPHOS via ONC201/TIC10 suppresses mitochondrial respiration and 2DG inhibits glycolysis, leading to energy depletion and enhanced anti-cancer activity	(132)
HSPD1	Synthetic small molecule (KHS101)	In vitro and in vivo study	Alteration of Mitochondrial bioenergetic capacity and glycolytic activity	(148)
NAD+	NAMPT inhibitors (GMX1778) NAMPT knockdown	In vitro and in vivo study In vitro study	NAD+ depletion alter tumor microenvironment Reduction of cell proliferation, migration, and invasion and induction of apoptosis	(149, 150)
Lipoxygenase (15-LOX)	15-Lipoxygenase Inhibitors (Luteolin and NDGA)	In vitro study	15-LOX inhibition reduced migration and raised cell cycle arrest in the G2/M phase	(151)