Methionine adenosyltransferase 2A (Mat2A) is responsible for the biosynthesis of S-adenosyl-L-methionine (SAM), an enzyme cofactor required for transmethylation reactions and polyamine biosynthesis. PF-9366 is an allosteric inhibitor of Mat2A with an IC50 value of 420±50nM. Pre-incubation of Mat2A with increasing concentrations of Mat2B (0–100nM) reduced the inhibitory effect of PF-9366 in a dose-dependent manner. PF-9366 inhibited SAM production in H520 cells with an IC50 value of 1.2μM. The IC50 of PF-9366 in H520 cells with Mat2B knockdown was 0.86mM. Six-hour exposure of PF-9366 inhibited SAM synthesis in Huh-7 cells with an IC50 value of 225nM[2].
PF-9366 细胞实验
Cell Line
Concentration
Treated Time
Description
References
HT22 mouse hippocampal neuronal cell line
25 µM
24 hours
Inhibition of MAT2A significantly decreased PRMT7 protein expression and activity, as indicated by reduced mono-methylarginine (MMA) production.
Neurochem Int. 2023 Jun;166:105524.
SKM-1 cells
12.75 µM (IC50)
6 days
Moderate impact on proliferation and viability
Cancers (Basel). 2020 May 24;12(5):1342.
THP-1 cells
4.210 µM (IC50)
6 days
Reduction of proliferation and viability
Cancers (Basel). 2020 May 24;12(5):1342.
SEM cells
3.815 µM (IC50)
6 days
Reduction of proliferation and viability
Cancers (Basel). 2020 May 24;12(5):1342.
CRISPR/Cas9-MLL-AF9 cells
10 µM
6 days
Reduction of proliferation and viability, suppression of histone methylation
Cancers (Basel). 2020 May 24;12(5):1342.
CRISPR/Cas9-MLL-AF4 cells
10 µM
6 days
Reduction of proliferation and viability, suppression of histone methylation
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