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Table 2 The inhibition of AR mutants by VPC-13566 and their activation by various steroids

From: Functional analysis of androgen receptor mutations that confer anti-androgen resistance identified in circulating cell-free DNA from prostate cancer patients

AR construct

IC50 of VPC-13566 Inhibition (μM)

EC50 of DHT activation (nM)

EC50 of estradiol activation (nM)

EC50 of progesterone activation (nM)

EC50 of hydrocortisone activation (nM)

WT

1.73

0.05

>500

104.0

>500

L702H

6.13

8.00

>500

172.0

25.0

V716M

1.06

0.14

>500

329 .0

>500

V731M

0.99

0.09

>500

115.0

>500

W742L

2.29

33.60

>500

>500

>500

W742C

3.43

4.74

>500

293.0

>500

H875Y

1.34

0.14

68.0

10.20

>500

H875Q

0.79

0.43

>500

>500

>500

F877L

0.37

0.08

>500

>500

>500

T878A

2.56

0.06

144.0

0.57

>500

T878S

0.43

0.02

100.0

0.53

>500

D880E

1.14

0.11

>500

177.0

>500

L882I

0.84

0.20

>500

>500

>500

S889G

10.48

0.37

230.0

17.20

>500

D891H

2.35

0.12

173.0

31.0

>500

E894K

1.20

0.25

>500

143.0

>500

M896V

0.59

4.50

>500

>500

>500

M896T

0.10

>500

>500

>500

>500

E898G

1.24

0.45

>500

>500

>500

T919S

1.29

0.03

>500

123.0

>500

H875Q/T919S

0.63

0.18

>500

>500

>500

T878A/S889G

13.20

0.12

94.0

0.36

>500

T878A/D891H

13.40

0.40

100.0

0.49

>500

H875Y/T878A

10.80

1.26

63.0

0.66

105.0

F877L/ T878A

11.70

0.81

>500

5.70

>500

  1. The IC50 values of the inhibition by VPC-13566 and the EC50 values of the activation by DHT, estradiol, progesterone, and hydrocortisone are reported for the wild-type AR and the 24 studied mutants. For steroid activation, we tested a concentration range up to 500 nM, therefore mutants showing no activation or very weak activation in the studied range are presented with EC50 values >500 nM