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GART is one of the enzymes that builds purines from scratch; pemetrexed blocks it alongside thymidylate synthase, which is why the drug starves fast-growing lung and mesothelioma cells.
The trifunctional protein GART carries three activities of de novo purine synthesis, including glycinamide ribonucleotide formyltransferase, a folate-dependent step. Pemetrexed, once polyglutamated inside cells, inhibits thymidylate synthase most strongly but also GART and dihydrofolate reductase, giving it a multi-targeted antifolate action in non-small cell lung cancer and mesothelioma.
In plain words · GART is one of the enzymes that builds purines from scratch; pemetrexed blocks it alongside thymidylate synthase, which is why the drug starves fast-growing lung and mesothelioma cells.
GART is one of the enzymes that builds purines from scratch; pemetrexed blocks it alongside thymidylate synthase, which is why the drug starves fast-growing lung and mesothelioma cells.
A cytosolic enzyme of the purine pathway whose activity rises with proliferation; inhibition depletes purine nucleotides needed for DNA and RNA.
No product in this corpus aims at GART (trifunctional purine synthesis enzyme) yet. Inhibitors are shaped to fit the enzyme's active site so the reaction the cancer relies on stops.
Broadly expressed or essential: HPA lists GART among essential proteins and finds the RNA at low tissue specificity; the 1 medicine aimed at it (Pemetrexed) act on the wild-type protein, so normal tissue is exposed and the therapeutic window comes from the tumour's faster division or its dependence on the protein. HPA GART: RNA low tissue specificity; no normal tissue stained high; highest cancer staining testis cancer (10 of 12 high). Distribution: 2 cancer families in the corpus carry a prevalence row, label threshold or catalogue link for it (Lung cancer (all types), Mesothelioma); Open Targets associates it with 3 specific cancer types at or above 0.5 (non-small cell lung carcinoma, mesothelioma, malignant pleural mesothelioma). (Rule 7 of scripts/fetch-target-specificity.ts.)
Sources: Human Protein Atlas GART tissue; Open Targets ENSG00000159131 associations
First described 1990. Earliest sequence paper UniProt cites for the protein: Aimi et al, Nucleic Acids Res, 1990, "De novo purine nucleotide biosynthesis: cloning of human and avian cDNAs encoding the trifunctional glycinamide ribonucleotide synthetase-aminoimidazole ribonucleotide synthetase-glycinamide ribonucleotide transformylase by functional complementation in E. coli". Source.
A cytosolic enzyme of the purine pathway whose activity rises with proliferation; inhibition depletes purine nucleotides needed for DNA and RNA.
RNA: low tissue specificity, detected in all normal tissues.
No normal tissue stained high; medium in Adrenal gland, Appendix, Bone marrow, Breast, Bronchus, Caudate and more.
Medium only: carcinoid, prostate cancer, renal cancer, thyroid cancer.
HPA GART tissue · HPA GART pathology · HPA protein class: Essential proteins, FDA approved drug targets
Human Protein Atlas version 25.1, antibody staining at reliability approved, enhanced or supported; used under CC BY-SA 3.0. Staining counts are patients per level in the atlas cohort, not population prevalence.
| Cancer | Prevalence | Measure | Note | Source |
|---|---|---|---|---|
| Metastatic cancer | all% | Housekeeping enzyme present in every dividing cell (purine synthesis); not a selection marker, which is why these drugs are given by cancer type rather than by test. |
Approximate, population-level figures; the measure column says what was counted. Ranges show the midpoint as a bar.
Query for this target: (TITLE:"GART" OR ABSTRACT:"GART" OR TITLE:"trifunctional purine synthesis enzyme" OR ABSTRACT:"trifunctional purine synthesis enzyme") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about GART (trifunctional purine synthesis enzyme), not a curated reading list.
Shares Mesothelioma, Pemetrexed.
Shares Thymidylate synthase (TYMS), Mesothelioma, Pemetrexed.
Shares Mesothelioma, Pemetrexed.
Shares Pemetrexed, Non-small-cell lung cancer.
Shares Pemetrexed, Non-small-cell lung cancer.
Shares Pemetrexed, Non-small-cell lung cancer.
Shares Mesothelioma, Non-small-cell lung cancer.
Shares Mesothelioma, Non-small-cell lung cancer.