. 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 1.

Biochemical and Cellular LDH Inhibition of 2–10 with Comparator 1



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

1		24	450	2454	636	8448	-
2		25	1423	4642	1721	1066	501
3		36	509	1959	804	6195	727
4		274	9719	148^b	19400	3168^b	15849
5		4104	20186	>30000	12791	>30000	303
6		36	1861	24440	4760	17706	2529
7	2-F	25	613	1144	867	3376	150
8	3-F	229	4465	11471	6465	5747	-
9	H	23	835	2647	1224	8448	401
10	F	23	465	1344	585	3416	141

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.)

Efficacy < 20% with curve class 4; therefore, it should be considered as inactive.