Table 6.
Analog | LDHA inh. | Lactate inh. | CETSA: Cellular LDHA stabilization | ||
---|---|---|---|---|---|
IC50 (μM) | IC50 (μM) | EC50 (μM)a | Max stab.b (norm’d) | AUCc (norm’d) | |
1 | 1.020 | >57 | 1.60 | 64.8 | 62.08 |
2 | 0.038 | - | 8.18 | 52.4 | 43.22 |
3 | 0.424 | 12.60 | 1.26 | 79.0 | 72.96 |
5 | 22.200 | - | >100 | 8.5 | 13.84 |
33 | 0.672 | >57 | 3.53 | 47.9 | 53.66 |
44 | 0.038 | 9.88 | 2.56 | 100.0 | 89.77 |
57 | 0.053 | 4.80 | >100 | 41.6 | 26.76 |
61 | 0.027 | 1.34 | 0.25 | 63.0 | 70.66 |
62 | 0.009 | 5.12 | 0.07 | 70.8 | 100.00 |
63 | 0.032 | 0.85 | 0.17 | 69.9 | 81.95 |
EC50 values represent the half maximal (50%) concentration (the concentration needed to stabilize half of the detectable LDHA protein at a set melting temperature) as determined by CETSA.
Maximum stabilization values represent the highest amount of stabilized LDHA detected for each sample, as measured by Western blot band intensity. These values are scaled against the band with the greatest amount of stabilized LDHA (maximum response of 44) to provide a relative measure of target binding.
Area-under-the-curve (AUC) values demonstrate the total amount of LDHA stabilized by each compound across all concentrations, scaled against the AUC of the compound with the greatest total amount of LDHA stabilization (62), again to provide a relative measure of LDHA engagement.