Guanosine triphosphate  (Synonyms: GTP)

Guanosine triphosphate (GTP) is a critical nucleotide and regulator of cellular metabolism. Guanosine triphosphate promotes ribosomal DNA localization, pre-rRNA transcription and ribosome biogenesis by binding to RNA polymerase I and GPN proteins (GPN1/3). Guanosine triphosphate links MYC-dependent ribosome biogenesis to nucleotide sufficiency, acts as a metabolic gatekeeper supporting protein synthesis, DNA/RNA synthesis and cellular signal transduction, while also participating in the physiological activities of pancreatic β-cells and serving as an oxidative substrate for reactive oxygen species. In small cell lung cancer with high MYC expression, Guanosine triphosphate accumulates through the IMPDH-driven synthetic pathway, thereby affecting apoptosis and mitotic processes. Guanosine triphosphate is used in the research of small cell lung cancer, hepatoblastoma and cellular metabolism^[1][2][3].

Primary MYC-high human small-cell lung cancer tumors have elevated endogenous guanosine triphosphate levels independent of proliferation status^[1].
Guanosine triphosphate (GTP depletion via 1 μM MPA; 12 h) reduced protein synthesis in chemoresistant DMS53-CR human small-cell lung cancer cells, while restoring guanosine triphosphate levels (20 μM guanosine; 12 h) rescued protein synthesis activity^[1].
Guanosine triphosphate binding to MYC-upregulated GPN1 and GPN3 GTPases is required for RNA polymerase I localization, ribosome biogenesis, and proliferation in MYC-high H82 human small-cell lung cancer cells, and constitutively GTP-bound GPN1/GPN3 mutants protect cells from guanosine triphosphate depletion-mediated inhibition of these activities^[1].
Depletion of cellular GTP (1 μg/ml mycophenolic acid; 1-24 h) in HIT-T15 insulin-secreting β-cells potently inhibits mitogenesis, with significant inhibition observed as early as 1 hour and near-complete inhibition after 6-24 hours of treatment^[2].
Depletion of cellular GTP (1.6-6.3 μg/ml mycophenolic acid; 18 h) in HIT-T15 and INS-1 insulin-secreting β-cells inhibits Ca²⁺-stimulated insulin secretion^[2].
Guanosine triphosphate (1 mM; 4 h at 37 °C) undergoes oxidation to oxo8GTP in the presence of a ROS-generating system (1 mM L-ascorbic acid + 10 μM cupric sulfate), with oxo8GTP levels increasing ~4-fold and GTP levels showing a small significant decrease relative to control^[3].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

523.18

C₁₀H₁₆N₅O₁₄P₃

86-01-1

O[C@H]1[C@@H](O)[C@H](N2C(N=C(N)NC3=O)=C3N=C2)O[C@@H]1COP(OP(OP(O)(O)=O)(O)=O)(O)=O

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• [1]. Huang F, et al. Guanosine triphosphate links MYC-dependent metabolic and ribosome programs in small-cell lung cancer. J Clin Invest. 2021;131(1):e139929.  [Content Brief]

  [2]. Li G, et al. Prolonged depletion of guanosine triphosphate induces death of insulin-secreting cells by apoptosis. Endocrinology. 1998;139(9):3752-3762.  [Content Brief]

  [3]. Bolin C, et al. Assessing biomarkers of oxidative stress: analysis of guanosine and oxidized guanosine nucleotide triphosphates by high performance liquid chromatography with electrochemical detection. J Chromatogr B Analyt Technol Biomed Life Sci. 2007;856(1-2):121-130.  [Content Brief]