Background
Results
B cell purity and TLR basal gene expression
Characterization of small molecule TLR7, TLR7/8, and TLR8 agonists
Compound | Minimum effective concentration (MEC, μM) for NFκB activation (a) | TLR selectivity (b) | |
---|---|---|---|
TLR7 | TLR8 | ||
3M-006
| Inactive (100) | Inactive (100) | None |
3M-003
| 0.1 | 1 | TLR7/8 @ 1 μM |
852A
| 3 | 100 | TLR7 @ 3 μM |
3M-002
| 10 | 1 | TLR8 @ 5 μM |
TLR agonist induced gene expression
Gene | Alias | 3M-006 | 3M-002 | 852A | 3M-003 | CpG 2006 | ||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
D1 | D2 | D3 | D1 | D2 | D3 | D1 | D2 | D3 | D1 | D2 | D3 | D1 | D2 | D3 | ||
FCGR2B
|
CD32
| -1.2 | -1.7 | -1.2 | -1.3 | -1.9 | -1.3 | -2.6 |
-4.7
| -2.1 |
-7.4
|
-19.1
|
-8.4
|
-6.7
|
-22.8
|
-8.6
|
GBP2
|
GBP2
| -1.1 | -1.5 | 1.0 | -1.1 | -1.9 | 1.0 | -2.8 |
-5.0
| -2.3 |
-3.5
|
-13.4
|
-7.1
| -2.6 | -1.7 | -1.8 |
CD72
|
Ly-19
| -1.5 | 1.2 | 1.4 | -1.1 | -1.2 | 1.4 | -3.2 |
-3.9
| -1.8 |
-5.1
|
-9.1
|
-4.4
|
-3.5
|
-5.8
| -2.9 |
GAPDH
|
GAPDH
| 1.0* | 1.0* | 1.0* | 1.0* | 1.0* | 1.0* | 1.0* | 1.0* | 1.0* | 1.0* | 1.0* | 1.0* | 1.0* | 1.0* | 1.0* |
IL12B
|
IL12p40
| -1.1 | 1.3 | 1.2 |
8.5
| 1.5 | 1.1 |
9.1
| -1.1 | 2.5 |
16.1
| 1.3 |
3.7
|
11.4
| -1.2 | 1.6 |
FCER2
|
CD23
| -1.1 | -1.4 | -1.3 | 1.6 | 1.4 | 1.5 | 3.1 | 1.7 | 2.9 |
7.0
| 2.3 |
5.4
|
3.5
| 1.1 |
3.7
|
CCL20
|
MIP3a
| -1.2 | -1.2 | 1.2 |
52.3
|
6.7
| 1.3 | 2.9 | -1.6 | 1.0 |
28.6
| 2.6 | 1.4 | -2.9 | -2.1 | 1.0 |
IL-1B
|
IL1F2
| -1.7 | -1.6 | -1.8 |
31.1
|
8.2
|
29.1
| 2.6 | 1.7 | 2.8 |
28.8
|
5.4
|
9.8
|
3.9
| -1.7 | 3.2 |
COX-2
|
PTGS2
| -1.2 | -2.8 | 1.3 |
21.7
|
5.0
| 2.0 | -2.7 | 2.0 | 2.7 |
16.8
|
3.6
|
5.6
|
4.9
|
8.3
| 2.2 |
CD86
|
B7-2
| -1.2 | -1.2 | 1.2 | 1.2 | 1.3 | 1.3 | 2.1 | 2.3 | 2.3 | 2.8 |
5.0
|
4.1
| 1.6 |
3.8
| 1.9 |
CD40
|
TNFRSF5
| 1.1 | 1.1 | 1.1 | 1.6 | 1.6 | 1.6 |
3.7
| 2.6 | 3.1 |
6.1
|
4.7
|
6.0
|
4.7
|
4.0
| 3.0 |
FOS
|
c-fos
| 1.1 | 1.4 | 1.6 | -1.3 | 1.6 | 1.8 | -2.0 | 2.8 | 2.7 |
-3.7
|
4.7
|
6.1
| -2.7 | -2.0 | -1.6 |
GOS-2
|
RP1
| -1.4 | -1.4 | 2.0 | 2.3 | 2.0 | 2.6 | 3.1 | 2.7 |
4.4
|
6.3
|
4.5
|
10.0
|
5.3
|
5.1
|
7.5
|
NFKB1A
|
IKBA
| 1.1 | 1.5 | 1.4 | 1.9 | 1.7 | 2.2 |
3.8
|
3.8
|
4.2
|
4.8
|
4.2
|
6.6
|
4.0
|
4.2
|
5.4
|
TR3
|
TNFRSF25
| 1.3 | 1.8 | 1.6 | 1.2 | 1.9 | 2.1 | 1.5 |
4.0
|
3.5
| -2.7 | 3.2 |
5.6
| 2.0 |
3.6
| -1.5 |
CD58
|
LFA3
| 1.1 | 1.2 | 1.2 | 1.3 | 1.5 | 1.6 | 2.0 |
3.8
| 3.2 | 3.3 |
4.8
|
5.0
| 3.2 |
5.2
|
5.5
|
IL21r
|
NILR
| 1.3 | 1.4 | 1.3 | 1.7 | 2.2 | 2.2 |
3.5
|
4.7
|
5.4
|
4.9
|
5.7
|
6.7
|
4.0
|
5.1
|
6.3
|
MYC
|
c-myc
| -1.2 | 1.4 | 1.4 | 1.6 | 1.7 | 1.9 | 2.1 |
3.7
| 3.2 |
3.5
|
7.0
|
10.7
|
3.6
|
12.3
|
8.1
|
CD80
|
B7-1
| 1.2 | 1.4 | 1.2 | 2.0 | 1.9 | 1.8 |
3.9
|
4.8
|
3.8
|
7.3
|
8.6
|
8.1
|
6.1
|
6.9
|
6.4
|
TNFa
|
TNFSF2
| -1.2 | 1.4 | 1.2 | 3.1 | 2.2 | 1.7 |
9.5
|
6.9
|
7.7
|
14.9
|
10.3
|
16.2
|
13.8
|
11.8
|
7.0
|
IL1a
|
IL1F1
| -1.7 | 1.5 | 1.2 | 2.5 |
4.5
| 1.5 |
4.0
|
4.3
| 2.8 |
5.7
|
11.4
|
6.8
|
4.6
|
11.7
| 2.9 |
CCL4
|
MIP1b
| 1.4 | 1.0 | 1.2 | 3.3 | 2.3 | 3.0 |
6.1
|
7.1
|
5.7
|
10.8
|
10.9
|
32.6
|
22.3
|
38.6
|
37.4
|
CCL3
|
MIP1a
| 1.2 | 1.2 | 1.5 |
4.5
| 2.4 | 2.9 |
11.4
|
10.0
|
10.1
|
18.9
|
15.6
|
45.6
|
39.3
|
45.6
|
62.3
|
BFCL2L1
|
Bcl-xl
| -1.3 | -1.1 | 1.3 | 1.9 | 1.8 | 2.1 |
4.5
|
8.3
|
6.4
|
6.1
|
21.7
|
15.1
|
5.1
|
12.8
|
9.2
|
DSP2
|
PAC1
| 1.3 | 1.5 | 1.2 | 1.2 | 2.8 | 2.0 | 2.3 |
10.8
|
4.6
|
4.0
|
16.1
|
18.3
|
3.7
|
13.5
|
5.0
|
LTA
|
TNFSF1
| 1.0 | 1.3 | 1.3 |
6.1
| 2.5 | 2.5 |
63.0
|
18.8
|
24.3
|
85.8
|
18.5
|
32.0
|
55.5
|
22.1
|
24.9
|
TCFL5
|
E2BP1
| -1.2 | 1.3 | 1.2 | 1.6 | 3.1 | 2.0 |
9.7
|
17.7
|
9.4
|
22.6
|
25.2
|
24.9
|
16.3
|
23.5
|
18.7
|
IL-6
|
IFNB2
| 1.9 | 2.4 | 1.0 |
7.0
|
4.7
|
6.1
|
24.9
|
25.6
|
40.4
|
70.8
|
51.3
|
71.9
|
58.9
|
59.4
|
53.2
|
Cytokine, chemokine and pro-inflammatory mediator genes
Gene | Alias | 3M-006 | 3M-002 | 852A | 3M-003 | CpG 2006 | ||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
D1 | D2 | D3 | D1 | D2 | D3 | D1 | D2 | D3 | D1 | D2 | D3 | D1 | D2 | D3 | ||
GAPDH
|
GAPDH
| 1.0* | 1.0* | 1.0* | 1.0* | 1.0* | 1.0* | 1.0* | 1.0* | 1.0* | 1.0* | 1.0* | 1.0* | 1.0* | 1.0* | 1.0* |
IFNa-2
|
IFNa-2
| 2.6 | 1.7 | 1.5 |
3.5
| 1.8 | 1.4 | 3.0 | -1.3 | 1.2 | -2.2 | -1.5 | -1.2 | 4.0 | -1.7 | -1.2 |
ISG15
|
ISG15
| 1.6 | 1.3 | 1.2 | 1.9 | 1.1 | 1.5 | 1.2 | 1.5 | 1.8 | 3.0 | -2.7 | 2.3 | -1.5 | -2.2 | -1.5 |
MX1
|
MX1
| 1.3 | -1.2 | 1.3 | 1.7 | -1.5 | 1.1 | 1.5 | -2.3 | -1.6 |
6.8
| -3.3 |
-4.2
|
-3.9
| -3.4 |
-4.3
|
TLR7
|
TLR7
| 1.5 | -1.2 | 1.6 | 1.2 | -1.3 | 1.3 | -2.8 | -2.7 | -1.6 | -2.9 | -2.1 |
-4.3
|
-3.5
|
-6.7
|
-4.5
|
TLR9
|
TLR9
| -1.3 | -1.2 | -1.1 | 1.0 | -1.3 | -1.1 | -1.9 | -1.5 | -1.4 | -3.1 |
-3.9
| -2.3 | -3.2 | -3.0 | -1.7 |