One of the major reasons for studying chemical kinetics is to use measurements of the macroscopic properties of a system, such as the rate of change in the concentration of reactants or products with time. 5399-92-8, Name is 4-Chloro-1H-pyrazolo[3,4-d]pyrimidine, formurla is C5H3ClN4. In a document, author is Neef, Sylvia K., introducing its new discovery. HPLC of Formula: C5H3ClN4.
Metabolic Drug Response Phenotyping in Colorectal Cancer Organoids by LC-QTOF-MS
As metabolic rewiring is crucial for cancer cell proliferation, metabolic phenotyping of patient-derived organoids is desirable to identify drug-induced changes and trace metabolic vulnerabilities of tumor subtypes. We established a novel protocol for metabolomic and lipidomic profiling of colorectal cancer organoids by liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QTOF-MS) facing the challenge of capturing metabolic information from a minimal sample amount (<500 cells/injection) in the presence of an extracellular matrix (ECM). The best procedure of the tested protocols included ultrasonic metabolite extraction with acetonitrile/methanol/water (2:2:1, v/v/v) without ECM removal. To eliminate ECM-derived background signals, we implemented a data filtering procedure based on the p-value and fold change cut-offs, which retained features with signal intensities >120% compared to matrix-derived signals present in blank samples. As a proof-of-concept, the method was applied to examine the early metabolic response of colorectal cancer organoids to 5-fluorouracil treatment. Statistical analysis revealed dose-dependent changes in the metabolic profiles of treated organoids including elevated levels of 2 ‘-deoxyuridine, 2 ‘-O-methylcytidine, inosine and 1-methyladenosine and depletion of 2 ‘-deoxyadenosine and specific phospholipids. In accordance with the mechanism of action of 5-fluorouracil, changed metabolites are mainly involved in purine and pyrimidine metabolism. The novel protocol provides a first basis for the assessment of metabolic drug response phenotypes in 3D organoid models.
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Reference:
Pyrimidine | C4H4N2 – PubChem,
,Pyrimidine – Wikipedia