Table 3: Ligand
binding profile of (S)-WIN-64338 at numerous receptors, enzymes, transporters
and ion-channels
|
Receptor |
Percent
Inhibition (Average;
N=2) |
||
|
1.0E-9M |
1.0E-7M |
1.0E-5M |
|
|
Neurotransmission
Related |
|
|
|
|
Adenosine
Transporter (h) |
11.72% |
7.40% |
39.83% |
|
Adenosine,
Non-selective |
13.17% |
17.40% |
17.74% |
|
Adrenergic,
Alpha 1, Non-selective |
19.80% |
22.63% |
94.64% |
|
Adrenergic,
Alpha 2, Non-selective |
11.72% |
10.26% |
46.46% |
|
Adrenergic,
Beta, Non-selective |
-0.94% |
8.97% |
3.74% |
|
Benzodiazepine,
peripheral (h) |
3.49% |
9.83% |
21.82% |
|
Cannabinoid,
CB1 (h) |
1.96% |
12.63% |
2.99% |
|
Cannabinoid,
CB2 (h) |
-4.87% |
1.64% |
9.42% |
|
Dopamine
Transporter (h) |
5.94% |
17.49% |
95.50% |
|
Dopamine,
Non-selective |
8.89% |
8.27% |
79.05% |
|
GABA,
Non-selective |
9.79% |
-6.91% |
11.02% |
|
GABA-B |
10.24% |
19.65% |
12.71% |
|
Glutamate,
AMPA Site (Ionotropic) |
4.81%% |
-11.82% |
8.26% |
|
Glutamate,
Chloride Dependent Site (Ionotropic) |
To be
determined |
||
|
Glutamate, Kinate Site (Ionotropic) |
-27.94% |
-11.37% |
-15.73% |
|
Glutamate,
MK-801 Site (Ionotropic) |
1.15% |
-8.53% |
4.46% |
|
Glutamate,
NMDA Agonist Site (Ionotropic) |
1.98% |
-0.84% |
-11.28% |
|
Glutamate,
NMDA, Phencyclidine Site (Ionotropic) |
11.73% |
-17.45% |
-11.81% |
|
Glutamate, mGluR5 (Metabotropic) |
9.79% |
6.48% |
9.35% |
|
Glutamate,
NMDA, Glycine (Stry-insens
Site) (Ionotropic) |
4.89% |
5.47% |
1.99% |
|
Glycine,
Strychnine-sensitive |
7.02% |
7.80% |
24.44% |
|
Histamine, H1 |
5.58% |
3.19% |
10.61% |
|
Histamine,
H2 |
3.60% |
8.75% |
103.21% |
|
Histamine, H3 |
-6.06% |
-0.96% |
10.00% |
|
Imidazoline,
I1 |
To be
determined |
||
|
Imidazoline,
I2 (Central) |
4.27% |
5.27% |
17.34% |
|
Melatonin,
Non-selective |
0.06% |
2.56% |
14.06% |
|
Muscarinic, Non-selective, Central |
5.09% |
23.32% |
96.53% |
|
Muscarinic, Non-selective, Peripheral |
16.61% |
19.05% |
74.94% |
|
Nicotinic,
Neuronal (a-BnTx insensitive) |
1.14% |
1.05% |
4.59% |
|
Nicotinic,
Neuronal (a-BnTx sensitive) |
2.30% |
3.57% |
20.06% |
|
Norepinephrine
Transporter |
7.65% |
8.47% |
28.77% |
|
Opioid,
Non-selective) |
-1.66% |
-0.38% |
76.24% |
|
Orphanin, ORL1 (h) |
-13.09% |
-7.38% |
73.69% |
|
Purinergic,
P2Y (h) |
7.31% |
6.81% |
-9.94% |
|
Serotonin
Transporter (h) |
-11.46% |
0.07% |
46.25% |
|
Serotonin,
5HT1, Non-selective |
2.12% |
0.13% |
11.45% |
|
Serotonin, 5HT2A (h) |
18.49% |
20.04% |
69.69% |
|
Serotonin, 5HT3 (h) |
-0.91% |
1.48% |
26.43% |
|
Serotonin, 5HT4 |
-5.08% |
5.69% |
79.29v |
|
Sigma,
Non-selective |
-6.10% |
-0.18% |
52.29% |
|
IMMUNOLOGICAL
FACTORS |
|
|
|
|
Complement, Anaphylatoxin,
C5a (h) |
-11.01% |
-6.68% |
-4.65% |
|
FKBP12 (FK-506
Binding Protien) (h) |
2.36% |
-7.75% |
17.23% |
|
STEROIDS
|
|
|
|
|
Estrogen (h) |
9.69% |
-2.68% |
6.65% |
|
Glucocorticoid
(h) |
To be
determined |
||
|
Progesterone
(h) |
To be
determined |
||
|
Testosterone (cytosolic) (h) |
14.24% |
-3.55% |
8.00% |
|
ION
CHANNELS |
|
|
|
|
Calcium
Channel, Type L (Benzothiazepine Site) |
7.72% |
31.13% |
76.17% |
|
Calcium
Channel, Type L (Dihydropyridine Site) |
1.50% |
9.37% |
89.24% |
|
Calcium
Channel, Type L (alpha -2-delta subunit) |
-0.69% |
0.76% |
19.77% |
|
Calcium
Channel, Type N |
--5.98% |
4.34% |
3.40% |
|
Potassium
Channel, ATP –Sensitive |
7.78% |
4.06% |
-4.37% |
|
Potassium
Channel, Ca2+ ACT., VI |
7.73% |
13.87% |
11.76% |
|
Potassium
Channel, I[kr] (hERG) (h) |
-4.86% |
6.43% |
85.94% |
|
Sodium, Site 2 |
-4.83% |
8.13% |
83.53% |
|
SECOND
MESSENGERS |
|
|
|
|
Adenylate Cyclase, Forskolin |
-3.91% |
-4.13% |
10.18% |
|
Inositol Triphosphate, IP3 |
0.72% |
-0.18% |
-5.57% |
|
Nitric oxide,
NOS (Neuronal-Binding) |
2.04% |
4.88% |
19.98% |
|
Protein
Kinase C, PDBu |
-14,
49% |
-1.95% |
54.53% |
|
PROSTAGLANDINS |
|
|
|
|
Leukotriene,
LTB4 (BLT) |
-0.75% |
3.24% |
-30.20% |
|
Leukotriene,
LTD4 (CysLT1) |
-3.96% |
-6.10% |
-11.25% |
|
Thromboxane A2
(h) |
6.06% |
7.44% |
19.84% |
|
GROWTH
FACTORS/HORMONES |
|
|
|
|
Atrial Natriuretic peptide, ANP A |
5.92% |
1.20% |
-82.29% |
|
Corticotropin
Releasing Factor, Non-selective |
12.10% |
-8.74% |
-4.78% |
|
Oxytocin |
13.92% |
17.80% |
19.57% |
|
Platelet
Activating Factor, PAF |
-4.95% |
14.37% |
15.04% |
|
Thyrotropin
Releasing Hormone, TRH |
9.44% |
11.27% |
9.18% |
|
BRAIN/GUT
PEPTIDES |
|
|
|
|
Angiotensin
II, AT1 (h) |
-0.35% |
1.89% |
5.35% |
|
Bradykinin, Bk2 |
11.42% |
60.43% |
97.85% |
|
Cholecystokinin, CCk1 (CCKA) |
5.54% |
4.97% |
72.83% |
|
Cholecystokinin,
CCk2 (CCKB) |
2.71% |
10.01% |
5.90 |
|
Endothelin,
ET-A (h) |
-12.36% |
-1.97% |
21.99% |
|
Endothelin,
ET-B (h) |
5.12% |
-6.34% |
-11.78% |
|
Galanin,
Non-Selective |
5.75% |
12.96% |
5.21% |
|
Neurokinin, NK1 |
-15.61% |
-2.76% |
74.71% |
|
Neurokinin, NK2 (NKA) (h) |
2.66% |
14.67% |
102.07% |
|
Neurokinin,
NK3 (NKB) |
9.25% |
6.38% |
40.96% |
|
Neuropeptide Y, Non-selective |
-3.76% |
2.30% |
74.58% |
|
Neurotensin
(h) |
-2.53% |
-3.69% |
-39.74% |
|
Somatostatin, Non-selective |
-12.41 |
-3.67% |
69.93% |
|
Vasoactive
Intestinal Peptide, Non-selective |
-7.01% |
4.00% |
4.08% |
|
Vasopressin 1 |
0.20% |
-9.86% |
-15.29% |
Each
value is the average of two determinations for each concentration of
(S)-WIN-64338 (1nM, 100nM and 10µM final).
The bolded values meet the criterion of at least 50% inhibition of ligand binding for at least one concentration of the test
compound. The negative value suggests an
apparent stimulation of binding. There
is a ± 15% variability associated with each ligand binding assay.