in vitro PHARMACOLOGY 2011 CATALOG - Cerep

74 in vitro pharmacology 2011 catalog
❚ somatostatin
sst 2 - agonist radioligand
binding
Ref. 2339
Q 6 weeks
Source
Ligand
Kd
Non specific
Reference
IMR32 cells (endogenous)
[ 125 I]Tyr 11 -somatostatin-14 (0.04 nM)
0.2 nM
seglitide (1 µM)
seglitide (IC 50 : 0.2 nM)
O’Dorisio, M.S. et al. (1994) Cell Growth Differ., 5: 1-8.
specific binding (% of control)
100
50
0
-12 -11 -10 -9 -8 -7 -6 -5
log [drug] (M)
seglitide
somatostatin-14
CYN 154806
BIM 23027
sst 4 - agonist radioligand
binding
Ref. 0482
Q 3 weeks
Included in:
BioPrint ® profile
Organ safety profile
Source
Ligand
Kd
Non specific
Reference
human recombinant (CHO cells)
[ 125 I]Tyr 11 -somatostatin-14 (0.1 nM)
5.9 nM
somatostatin-14 (1 µM)
somatostatin-14 (IC 50 : 1.4 nM)
Rohrer, L. et al. (1993) Proc. Natl. Acad. Sci. USA, 90: 4196-4200.
specific binding (% of control)
100
50
0
-11 -10 -9 -8 -7 -6 -5
log [drug] (M)
▲ somatostatin-14
● [D-Trp 8 ]-
somatostatin
■ somatostatin-28
▼ BIM 23056
sst 4
cellul ar
Ref. 2095
Ref. 2103
Q 3 weeks
Agonist effect
Antagonist effect
Source
human recombinant (CHO cells)
Measured product cAMP
Detection method HTRF
Agonist effect Control somatostatin-14 (100 nM)
Reference somatostatin-14 (EC 50 : 0.21 nM)
Antagonist effect Stimulant somatostatin-14 (3 nM)
Reference unavailable
Engström, M. et al. (2005) J. Pharm. Exp. Ther., 312: 332-338.
[Solvent] must be kept 0.3%
sst 5 - agonist radioligand
Source
human recombinant (CHO cells)
Ligand
[ 125 I]Tyr 11 -somatostatin-14 (0.1 nM)
binding
Kd
0.2 nM
Ref. 0626
Non specific somatostatin-14 (1 µM)
Q 3 weeks
Reference somatostatin-14 (IC 50 : 0.76 nM)
Included in:
Organ safety profile
Yamada, Y. et al. (1993) Biochem. Biophys. Res. Commun., 195: 844-852.
specific binding (% of control)
100
50
0
log [drug] (M)
-13 - 12 -11 - 10 -9 -8 -7 -6
somatostatin-14
[D-Trp 8 ]-
somatostatin
somatostatin-28
BIM 23056
sst 5
cellul ar
Ref. 2087
Ref. 2088
Q 3 weeks
Agonist effect
Antagonist effect
Source
human recombinant (CHO cells)
Measured product cAMP
Detection method HTRF
Agonist effect Control somatostatin-14 (300 nM)
Reference somatostatin-14 (EC 50 : 6.1 nM)
Antagonist effect Stimulant somatostatin-14 (100 nM)
Reference unavailable
Carruthers, A.M. et al. (1999) Brit. J. Pharmacol., 126: 1221-1229.
[Solvent] must be kept 0.3%
For some binding assays two models are available using either agonist or antagonist as radioligand.
❚ For radioligand binding assays, how should I choose between the agonist and the antagonist models when both are
available?
G-protein-coupled receptors have both high-affinity and low-affinity states that are bound differently by agonists and antagonists. Whereas
the antagonists bind with an equal affinity to both affinity states, agonists bind poorly to the low affinity state of the receptor. Therefore,
it is advisable to use an antagonist radioligand to evaluate the binding of antagonists knowing that this may fail to reveal the binding
of agonists. On the other hand, an assay using an agonist radioligand is suitable to evaluate both agonists and antagonists.
The testing of a compound in both assays and the comparison of its competition curves against each radioligand may provide information
about its functional activity at the receptor.