Table 2.
Biological evaluation at CCK receptors
| Functional analysisa |
Binding affinityb (ki,
nM) |
||||
|---|---|---|---|---|---|
| Drug | hCCK-A EC50 (nM) | hCCK-B EC50 (nM) | hCCK-A [125I] CCK8 | hCCK-B [125I] CCK8 | CCK-A agonist activityc |
| SNF9007 | n/d | n/d | 3300 | 2.1 | n/d |
| RSA501 | 790 | 3100 | 140 | 14 | None |
| JMN1 | NA | 4.1 | 740 | 70 | None |
| JMN2 | NA | 6.9 | 1200 | 100 | None |
| JMN3 | NA | 2.3 | 2400 | 16 | None |
| JMN4 | NA | 1.9 | 810 | 11 | None |
| JMN5 | NA | 160 | 1800 | 1400 | None |
| JMN6 | NA | NA | >10,000 | >10,000 | None |
n/d = not determined, NA = no activity at 10−5 M.
a
Phosphoinositide (PI) hydrolysis assay in hCCK-A and hCCK-B receptors in HEK cell lines.
b
Competition against [125I] CCK8 (sulfated) in hCCK-A and hCCK-B receptors in HEK cell lines in the presence of naloxone.
c
Contraction of isolated tissue relative to initial contraction with KCl in the presence of naloxone in GPI/LMMP.