Table 1.

Selected small molecules with potential for clinical translation in CRC

Pathway	Target	Representative drugs	Comments	Most advanced clinical phase	Trial ID
Glycolysis	GLUT1	BAY-876	Inhibitor	Preclinical	NA
		STF-31	Inhibitor	Preclinical	NA
	HK	2-Deoxy-D-glucose	Competitive HK1 inhibitor	Preclinical	NA
		Lonidamine	HK2 inhibitor	Preclinical	NA
		3BP	HK2 inhibitor	Preclinical	NA
	PFKFB3	PFK-158	Inhibitor	Phase 1	NCT02044861
	PKM2	Shikonin	Inhibitor	Preclinical	NA
		TEPP-46	Activator	Preclinical	NA
	LDHA	GNE-140	Inhibitor	Preclinical	NA
TCA cycle	PDH	CPI-613	PDK activator	Phase 1&2	NCT01832857 NCT02232152 NCT02232152
		DCA	PDK2 inhibitor	Phase 1	NCT00566410
		Vitamin C	PDK1 inhibitor	Phase 1&2	NCT04035096
	IDH	AG-221	IDH2 inhibitor	Phase 1&2	NCT02273739
		AG-120	IDH1 inhibitor	Phase 2	NCT04056910
Pentose phosphate pathway	G6PD	RRx-001	Inhibitor	Phase 2	NCT02096354
		G6PDi-1	Inhibitor	Preclinical	NA
	ME	NPD389	ME2 Inhibitor	Preclinical	NA
Glutamate and Glutamine metabolism	GLS	CB-839	Allosteric inhibitor	Phase 1&2	NCT02861300 NCT03965845 NCT03263429
	GPT	Aminooxyacetate	Pan-aminotransferase inhibitor	Preclinical	NA
	ASCT2	V-9302	Aantagonist of glutamine transporter	Preclinical	NA
	xCT	Sulfasalazine	Ferroptosis inducer	Phase 3	NCT01198145
SGOC metabolism	PHGDH	NCT-503	Non-competitive inhibitor	Preclinical	NA
	SHMT	SHIN1	Dual SHMT 1/2 inhibitor	Preclinical	NA
	MTHFD2	LY345899	Folate analogue	Preclinical	NA
Tryptophan metabolism	IDO1	1-L-MT	Competitive inhibitor	Phase 1	NCT05469490 NCT00739609
		Epacadostat	Specifical inhibitor	Phase 1&2	NCT02178722 NCT03361228 NCT02327078 NCT03516708 NCT03182894
	TDO	HTI-1090	Dual IDO1/TDO inhibitor	Phase 1	NCT03208959
	AhR	BAY2416964	AHR antagonist	Phase 1	NCT04069026 NCT04999202
		IK-175	AHR antagonist	Phase 1	NCT04200963
Fatty acid metabolism	ACLY	NDI-091143	Inhibitor	Preclinical	NA
	ACC	Soraphen A	Inhibitor	Preclinical	NA
	FASN	TVB-2640	Inhibitor	Phase 1	NCT02980029
	ACSL	Triacsin C	PUFA analog	Preclinical	NA
	SCD1	A939572	Inhibitor	Preclinical	NA
Cholesterol metabolism	CPT1	Perhexiline	Inhibitor	Preclinical	NA
	SREBPs	Fatostatin	SREBP activity inhibitor	Preclinical	NA
	ACAT1	CI-976	Competitive inhibitor	Preclinical	NA
	HMGCR	Simvastatin	Competitive inhibitor	Phase 2&3	NCT00994903 NCT02161822 NCT01238094 NCT02026583 NCT01110785 NCT00313859
		Rosuvastatin	Competitive inhibitor	Phase 1&2&3	NCT02569645 NCT01011478 NCT05368805
	LXR	LXR623	LXR agonist	Preclinical	NA
		GW3965	LXR agonist	Preclinical	NA
Nucleotide metabolism	DHODH	Leflunomide	Inhibitor	Phase 1	NCT04997993
	TS	5-fluorouracil	TS inhibitor	Phase 1&2&3&4	NCT02582970 NCT00932438 NCT00046995