in vitro PHARMACOLOGY 2011 CATALOG - Cerep

82 in vitro pharmacology 2011 catalog
❚ NON-steroid nuclear receptors
PXR - agonist radioligand
Source
human recombinant (insect cells)
Ligand
[ 3 H]SR 12813 (35 nM)
Kd
35 nM
Non specific SR 12813 (30 µM)
binding
Ref. 2538
Reference T0901317 (IC 50 : 80 nM)
Q 3 weeks
Zhu, Z. et al.(2004) J. Biomol. Screen., 9: 533-540.
RARa - agonist radioligand
Source
human recombinant (insect cells)
Ligand
[ 3 H]9-cis retinoid acid (1 nM)
Kd
1 nM
Non specific all-trans retinoid acid (1 µM)
binding
Ref. 2084
Reference all-trans retinoid acid (IC 50 : 6.5 nM)
Q 3 weeks
Boehm, F.M. et al. (1994) J. Med. Chem., 37: 408-414.
specific binding (% of control)
100
50
all-trans-retinoic
acid
TTNPB
LE 135
9-cis-retinoic
0
acid
-11 -10 -7 -6 -5 -4
-9 -8
log [drug] (M)
TR (TH) - agonist radioligand
binding
Ref. 0156
Q 3 weeks
Included in:
BioPrint ® profile
Source
Ligand
Kd
Non specific
Reference
rat liver
[ 125 I]T 3 (0.1 nM)
0.24 nM
T 3 (1 µM)
T 3 (IC 50 : 0.44 nM)
Inoue, A. et al. (1983) Anal. Biochem., 134: 176-183.
specific binding (% of control)
100-10 -9 -8 -7 -6 -5 -4 -3
-12 -11 -10 -9 -8 -7 -6 -5 -4
50
-10 -9 -8 -7 -6
0 -10 -9 -8 -7 -6 -5 -4
-12 -11 -10 -7
-9 -8
log [drug] (M)
-9 -8 -7 -12 -11 -10 -6 -5
T 3
VDR - agonist radioligand
Source
human recombinant (Sf9 cells)
Ligand
[ 3 H]1α,25-(OH) 2 D 3 (0.3 nM)
Kd
1.7 nM
Non specific 1α,25-(OH) 2 D 3 (100 nM)
binding
Ref. 0499
Reference 1α,25-(OH) 2 D 3 (IC 50 : 3.4 nM)
Q 4 weeks
Ross, T. K. et al. (1991) Proc. Natl. Acad. Sci. USA, 88: 6555-6559.
specific binding (% of control)
100
50
0
-10 -9 -8 -7 -6 -5
log [drug] (M)
1α,25-(OH)2D3
1α-(OH)D3
25-(OH)D3
❚ For radioligand binding assays, how should I choose between the agonist and the antagonist models when both are
available?
For some binding assays two models are available using either agonist or antagonist as radioligand.
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.