. 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 2.

Biochemical and Cellular LDH Inhibition of Analogues 11–49



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

11	H	9	902	4346	660	4025	253
12	CH₃	11	505	332	450	322	119
13	Et	14	487	716	470	662	112
14	n-Pr	24	420	833	361	746	106
15	n-Bu	50	405	773	298	845	106
16		21	284	1011	487	756	2053
17		16	141	935	137	845	75
18		3	2475	1798	1659	1327	577
19		8	769	1225	525	1092	119
20		54	284	935	487	909	89
21		9	695	132	554	323	100
22		23	378	593	428	573	133
23		22	509	100	333	314	112
24		33	450	689	454	593	95
25		7	1931	2187	1479	2178	150
26		10	1052	1177	898	1236	84
27		7	1324	2647	1047	2263	126
28		6	12241	3587	4873	2994	1499
29		7	1268	973	831	1224	89
30		1	1056	1054	867	882	201
31		5	5937	2635	3871	1738	815
32		15	12241	9052	8910	17302	2579
33	CN	15	4010	>30000	4401	>30000	474
34	CF₃	450	>30000	>30000	>30000	>30000	14005
35	CF₂H	15	937	1482	741	1327	163
36		14	800	1134	822	1020	127
37		31	234	1016	259	1030	89
38		202	487	939	424	848	178
39		8	1086	973	1007	1102	267
40		9	933	1380	937	1225	178
41		107	15349	5834	18852	18061	5045
42		32	438	265	307	268	89
43 (NCATS-SM1440)		57	873	119	403	257	106
44		47	544	528	547	552	79
45		713	529	743	507	665	10602
46		33	937	569	867	488	-
47		52	1324	803	1603	909	170
48		8	1597	1542	1066	1387	299
49		9	1603	593	1141	619	189

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.)