Table 2 Preclinical KDM5 inhibitors in breast cancer

1

Metal-based complexes

MDA-MB-231 = 90.1 nM

4T1 = 68.2 nM

MCF-7 = 0.27 µM

MCF-10 A = 1.0 µM

HEK293T = 3.6 µM

LO2 = 4.7 µM

KDM5A = 23.2 nM

-

145

2

Natural product

MDA-MB-231 = 0.54 µM

MDA-MB-468 = 0.71 µM

MCF-7 = 2.26 µM

MCF-10 A = 8.21 µM

LO2 > 10 µM

KDM5A = 23.8 nM

KDM4A = 100 µM

-

146

3

Pyrimidinones

MCF-7 > 31.6 µM

T-47D > 25 µM

EFM-19 > 15 µM

KDM5A = 10 nM

KDM5B = 3 nM

KDM5C = 14 nM

KDM2B > 25 µM

KDM3B > 25 µM

KDM4C = 2 µM

PC9 > 25 µM,

Hs888 > 25 µM,

Colo205 > 25 µM

147, 148

4

Thiotriazoles

-

KDM5A = 1.32 µM

KDM5B = 50 µM

KDM5C = 6.56 µM

KDM6A > 50 µM

KDM6B > 50 µM

-

149

5

Thiotriazoles

ZR-75-1 < 100µM,

MDA-MB-231 > 100 µM

KDM5A = 2.66 µM

KDM5B = 50 µM

KDM5C = 7.12 µM

KDM6A > 50 µM

KDM6B > 50 µM

Hela > 100 µM

149

6

Pyrazolylpyridine derivative

ZR-75-1 = 90 nM

KDM5A = 13 nM

KDM5B = 2 nM

KDM4C = 41 nM

KDM6B = 2.3 µM

KDM1A > 40 µM

KDM2A = 0.82 µM

KDM2B = 0.63 µM

-

150, 151

7

KDM5-Inh1

patent Number: WO 2014/131,777 A1

-

BT-474 < 0.1 µM,

SK-BR-3 < 1 µM

KDM5A = 4.3 nM

KDM5B = 0.28 nM

KDM5C = 6.4 nM

KDM4A = 7.6 nM

KDM4B = 6.4 nM

KDM4C = 6.0 nM

KDM6A = 6200 nM

KDM6B = 6200 nM

KDM7B = 400 nM

-

122

8

Isothiazolones

UACC-812 < 10 µM

KDM5A = 6.01 µM

KDM5B = 4.08 µM

KDM5C = 4.92 µM

-

152

9

Aminomethylpyridines

MDA-MB-231 < 1 µM

BT549 < 5 µM

MDA-MB-468 < 5 µM

MDA-MB-453 > 10 µM

KDM5A = 71 nM

KDM5B = 19 nM

KDM5C = 69 nM

KDM5D = 69 nM

KDM2B = 4400 nM

KDM4C = 4800 nM

HeLa = 50 µM

MM1S = 30 µM

118, 153 154

10

Thioamides

MCF-7 > 3 µM

KDM5B = 2.5 µM

KDM5C = 2 µM

HeLa < 30 µM

154, 155

11

Thioamides

MCF-7 > 3 µM

KDM5 = 1 µM

-

154

12

2,4-PDCA analog

-

KDM5A = 7 nM

KDM5B = 4 nM

KDM5C = 13 nM

KDM5D = 15 nM

-

101, 156

13

2,4-PDCA analog

MCF-7 = 5 µM

-

MM.1 S = 20 µM

101, 141, 156

14

Pyrimidinones

-

KDM5A = 15.1 nM

PC9 = 340 nM

101, 157