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. 2021 Apr 24;13(9):2061. doi: 10.3390/cancers13092061

Figure 4.

Figure 4

(a) Kinetic scheme for the inhibition of hTS (E) by FdUMP (d) and RTX (m); D represents the dUMP substrate, M the mTHF cofactor; (b,c) blue symbols: single-inhibitor Dixon-type plots for FdUMP (b) and RTX (c) alone; red symbols: Dixon-type plots for the inhibition by combinations of FdUMP with RTX 120 nM (b) and of RTX with FdUMP 450 nM (c). vo (rate without inhibitors) = 16 μM min−1. The curves only represent exponential-function fittings of the data. (d) Tight-binding analysis of the single-compound inhibition data of hTS by FdUMP (red symbols, LFdUMP) and RTX (blue symbols, 5 LRTX). v is the reaction rate, LFdUMP and LRTX are the left members in Equations S1 and S2 in the Supplementary Information. The values of LFdUMP reported in the plot were calculated assuming KM’ = 5 KM. (e) Isobologram showing the combination indexes (CI, see the text) for RTX/FdUMP combinations giving the fractional inhibitions (fi = 1 − v/v0) reported. Blue circles: [FdUMP] = 450 nM, [RTX]/nM = 55 (fi = 0.4), 70 (fi = 0.5), 120 (fi = 0.6), 180 (fi = 0.7), 260 (fi = 0.8); red circles: [RTX] = 120 nM, [FdUMP]/nM = 100 (fi = 0.4), 300 (fi = 0.5), 450 (fi = 0.6), 650 (fi = 0.7), 1000 (fi = 0.8). The curve is just a quadratic-function fitting to the CI/fract.inhib. data points. A typical estimated error bar is shown.