Table 3.

Compounds that synergize with glutamine catabolism inhibitors.

Small Molecule Inhibitors Targeting Glutaminolysis	Compounds that Synergize with Glutamine Catabolism Inhibitors	Cell Line	Results and Cellular Target/Mechanism	Reference
BPTES [bis-2-(5-phenylacetamido-1,2,4-thiadiazol-2-yl)ethyl sulfide]	shRNA silencing glutamine transaminase K (GTK)	Pancreatic cancer	Result: Decreased intracellular glutamate level and inhibited cell growth.  Target: GTK.	[14]
	2-(Phosphonomethyl)-pentanedioic acid [2-PMPA]	Patient-derived ovarian and pancreatic orthotopic tumors	Result: Reduced tumor growth.  Target: GCPII.	PubChem CID: 10130754 URL: https://pubchem.ncbi.nlm.nih.gov/compound/10130754#section=2D-Structure [14]
	Gemcitabine	Pancreatic ductal adenocarcinoma (PDAC)	Result: Combination therapy did not improve single treatment efficacy.  Target: DNA replication.	PubChem CID: 60750 URL: https://pubchem.ncbi.nlm.nih.gov/compound/60750#section=2D-Structure [13,96]
	Metformin	Pancreatic and prostate cancer	Results: Greater decrease in cancer cell number and decreased levels of lactate, glucose-6-phosphate, glucose-1-phosphate, and UDP-glucose (pancreatic).  Target: glucose metabolism	PubChem CID: 4091 URL: https://pubchem.ncbi.nlm.nih.gov/compound/4091#section=2D-Structure [13,85]
CB-839 (Telaglenastat)	Paclitaxel	TNBC and a basal HER2+ cell line	Result: Reductions in tumor growth and suppressed regrowth of tumor.  Mechanism: Inducing ER stress which promotes degradation of SLC1A5 by ubiquitin ligase RNF5	PubChem CID: 36314 URL: https://pubchem.ncbi.nlm.nih.gov/compound/36314#section=2D-Structure [97,98]
	Olaparib	Ovarian cancer and renal cell carcinoma	Result: Potently synergistic cell death.  Target: poly (ADP-ribose) polymerase (PARP)	PubChem CID: 23725625 URL: https://pubchem.ncbi.nlm.nih.gov/compound/23725625#section=2D-Structure [11,60]
	Erlotinib	EGFR mutant nonsmall cell lung cancer	Result: In vitro apoptosis and reduced in vivo tumor growth.  Target: EGFR tyrosine kinase	PubChem CID: 176870 URL: https://pubchem.ncbi.nlm.nih.gov/compound/176870#section=2D-Structure [61]
	ABT-199	Myeloid leukemia	Result: Killing acute myeloid leukemia blasts.  Target: BCL-2	PubChem CID: 49846579 URL: https://pubchem.ncbi.nlm.nih.gov/compound/49846579#section=2D-Structure [65]
	Nivolumab	Clear cell renal cell carcinoma	Result: Activation of T cells and proposed synergistic effects.  Target: G4 PD-1 immune checkpoint	[63]