Table 2

Isoform specificity of some of the phosphatidylinositol 3-kinase (PI3K) inhibitors in clinical development

IC50 (nM)

α

E545K

H1047R

β

δ

γ

mTOR

Reference


Pan-isoform PI3K inhibitors

XL147

39

-

-

383

36

23

> 15,000

[6]

BKM120

52

99

58

166

116

262

2,866

[139]

GDC-0941

3

3

3

33

3

75

580

[140]

PX-866

39

-

-

88

124

183

-

[13]

BAY 80-6946

0.5

-

-

3.7

0.7

6.4

-

[11]

CH5132799

14

6.7

56

120

500

36

-

[12]

Dual pan-isoform PI3K and mTOR inhibitors

XL765

39

-

-

113

43

9

190/908

[14]

BEZ235

4

5.7

4.6

75

7

5

20.7

[16,141]

PF-04691502*

1.8

-

-

2.1

1.6

1.9

16

[142]

PF-05212384

0.4

0.6

0.8

6

8

6

1

[143]

GDC-0980

4.8

-

-

27

6.7

14

17

[144]

GSK2126458*

0.019

0.0078

0.0094

0.13

0.024

0.06

0.18/0.3

[18]

BGT-226

4

-

-

63

-

38

-

[24]

PI3Kα-specific inhibitors

BYL719

5

4

5

1,156

290

250

> 9,100

[145]

PI3Kβ-specific inhibitors

GSK2636771

-

-

-

5.2

58

-

-

[86]

PI3Kδ-specific inhibitors

GS-1101 (CAL-101)

820

-

-

565

2.5

89

> 1,000

[46]

AMG319

-

-

-

-

< 10

-

-

[52]


A dash indicates no data available.

mTOR = mammalian target of rapamycin.

Ki*: binding affinity

Brana and Siu BMC Medicine 2012 10:161   doi:10.1186/1741-7015-10-161

Open Data