. 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 3.

Biochemical and Cellular LDH Inhibition of Analogues 50–67



Compd No.		Biochemical LDHA IC₅₀ (nM)^a	A673 cells		MiaPaCa-2 cells		HEK293 Cells
Compd No.		Biochemical 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

50	CH₃	9	713	695	525	619	150
51		47	298	419	281	377	89
52 (NCATS-SM1441)		40	760	105	367	347	119
53		101	390	419	417	452	119
54		87	494	359	657	332	95
55		385	296	528	203	590	179
56		201	403	332	434	342	183
57		169	333	347	491	905	270
58		167	218	452	408	556	113
59		154	345	528	286	528	134
60		434	485	833	337	803	113
61		36	450	285	432	296	168
62		12	525	552	450	671	119
63		17	527	309	487	360	90
64		43	713	532	720	641	38
65		13	1174	347	1180	471	101
66		137	345	528	218	533	201
67		235	161	716	218	810	299

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.)