. Author manuscript; available in PMC: 2021 Jan 25.

Published in final edited form as: J Med Chem. 2020 Sep 27;63(19):10984–11011. doi: 10.1021/acs.jmedchem.0c00916

Table 5.

Biochemical and Cellular LDH Inhibition of Analogues 74–89



Compd No.	X	Biochem LDHA IC₅₀ (nM)^a	A673 cells		MiaPaCa-2 cells		HEK293 Cells
Compd No.	X	Biochem LDHA IC₅₀ (nM)^a	lactate inh IC₅₀ (nM)^a	Cytotox IC₅₀ (nM)^a	lactate inh IC₅₀ (nM)^a	Cytotox IC₅₀ (nM)^a	CETSA IC₅₀ (nM)^a

74	F	202	390	218	197	226	200
75	H	117	174	187	172	171	152
76	H	52	547	137	417	137	95
77	H	160	434	197	254	223	142
78	H	306	434	320	387	265	189
79	H	636	572	571	379	496	299
80	H	33	364	180	417	173	84
81	H	24	434	218	334	218	17756
82	H	24	300	219	253	219	90
83	H	487	162	402	188	402	299
84	-	874	685	968	1027	9350	708
85	-	4540	18264	5899	5144	7427	10751
86	-	307	346	590	409	1049	251
87	-	122	485	526	459	469	175
88	-	1174	364	4686	515	5258	1027
89	-	5270	1864	26351	1219	20931	3183

IC₅₀ values represent the half maximal (50%) inhibitory concentration as determined in the HTS assay using a dose response in the 1536-well format. (n = 2 for lactate and n = 3 for cytotoxicity, CETSA, and biochemical LDHA.)