Table 1 Small-molecule inhibitors of SGOC metabolism

PHGDH

BI-4924

Competitive inhibitor

Experimentala and cancer/preclinical

[137]

PHGDH

CBR-5884

Inhibition of de novo serine synthesis

Experimentala and cancer/preclinical

[138]

PHGDH

NCT-503

Inhibition of de novo serine synthesis

Experimentala and cancer/preclinical

[139]

PHGDH

PKUMDL-WQ-2201

PHGDH allosteric inhibitor

Experimentala and cancer/preclinical

[140]

PHGDH

Azacoccone E

Non-competitive inhibitor

Cancer and other diseases /preclinical

[141]

PHGDH

Ixocarpalactone A

PHGDH allosteric inhibitor

Cancer and other diseases /preclinical

[142]

PSPH

Clofazimine

Competitive inhibitor

FDA approved treatment for leprosy and tuberculosis

[143]

PSPH

Glycerophosphorylcholine

Non-competitive inhibitor

Clinical Trials, Dementia/preclinical

[144]

SHMTs

SHIN1

Inhibition of glycine and CH₂-THF generation

Cancer and other diseases /preclinical

[145]

SHMT1/2

GART

AGF347

Inhibition of glycine and CH₂-THF generation

NSCLC, colon,

Pancreatic/ preclinical

[146]

SHMT1/2

2.12

Competitive inhibitor

Lung cancer/ preclinical

[147]

MTHFD2

LY345899

Induction of apoptosis through reduced mitochondrial NADP(H) generation

Colorectal cancer/preclinical

[148]

MTHFD1/2

Carolacton

Inhibition of both substrate and cofactor binding in active site

Colon, endocervical cancer cell/preclinical

[149]

TYMS

DHFR

GART

Pemetrexed

Inhibition of cell proliferation by limiting thymidylate for DNA synthesis

Various solid and hematological tumors/Approved

[150]

TYMS, DHFR

Methotrexate

Induction of cell death by depleting THF levels

FDA- approved for rtheumatoid arthritis,

and neoplastic diseases

Osteosarcoma Phase II

[151]

TYMS

5-FU

Inhibition of DNA synthesis by blocking conversion of dUMP to dTMP

Various solid and hematological tumors/Approved

[152]

FOLR1

Farletuzumab

Monoclonal antibody of IgG1κ

Competitive inhibitor

Ovarian cancer/

Phase I

Phase II

Phase II

[153,154,155]

DHFR

Trimetrexate

Inhibition of the production of DNA and RNA precursors and lead to cell death

Bacterial infection、cancers/ Phase II

[156]

DHFR/ TYMS

Raltitrexed

Reduction of dTMP level, and increase of dUMP level

Approved by European Medicines Agency (EMA) to treat colorectal cancer/Phase IV

HNSCC

Phase IV

[157]

DHFR

Piritrexim

Direct inhibition of DNA incorporation of deoxyuridine nucleoside

Bladder cancer/Phase II

[158]

TYMS

ZD-9331

 A water-soluble non-polyglutamatable TYMS inhibitor

Ovarian cancer/Phase II

[159]

TYMS

GS7904L

Inhibition of DNA synthesis by blocking conversion of dUMP to dTMP

Colorectal cancer/Phase I, HNSCC/Phase II, Advanced Solid Tumors/Phase I, Gastric cancer /Phase II, Locally Advanced or Metastatic Adenoma of the Biliary Tract/Phase II

[160]

TYMS

ONX-0801

 A cyclopenta[g]quinazoline-based inhibitor

Advanced Solid Tumors /Phase I

[161]

MAT2A

AG-270

Allosteric inhibitors

Advanced Solid Tumors and Lymphoma/Phase I

[162]

GART

Lometrexol

Inhibition of de novo purine synthesis

Lung Cancer/Phase I

[163]

CBS/CSE

aminooxyacetic acid

Inhibition of aspartate aminotransferase activity

Experimentala and cancer/preclinical

 [164]