Description
SC-51089 (146033-02-5) is a prostaglandin E2 (EP1 receptor) antagonist (pA2=6.5, guinea pig ileum muscle strip assay )1,4. Possesses analgesic activity in vivo (rodent ED50= 6.8 mg/kg)1,2,4. SC-51089 does not inhibit COX11 and does not block PGE1 induced hyperalgesia3.
Chemical Properties
Off-White Solid
Uses
A selective EP1 prostanoid receptor antagonist that attenuates prostaglandin E2-induced neuronal cell death in vitro and slows tumor growth in vivo. Its neuroprotective effect may potentially have therapeutic application in human stroke.
Uses
8-Chloro-dibenz[b,f][1,4]oxazepine-10(11H)-carboxylic acid 2-[1-oxo-3-(4-pyridinyl)propyl]hydrazide monohydrochloride is a potent and selective antagonist of EP1 receptors.
Biological Activity
Selective EP 1 prostanoid receptor antagonist (K i values are 1.3, 11.2, 17.5, 61.1, > 100, > 100, > 100, >100 and > 100 μ M for EP 1 , TP, EP 3 , EP 2 , EP 4 , FP and DP receptors respectively). Attenuates PGE 2 -induced neuronal cell death in vitro and slows tumor growth in vivo .
in vivo
SC 51089 (40 μg/kg; infused i.p. for 28 d) ameliorates motor coordination and balance dysfunction and rescues long-term memory deficit in R6/1 mouse model of HD[3].
| Animal Model: | R6/1 mouse model of Huntington's disease (HD), from 13 to 18 weeks of age[3] |
| Dosage: | 40 μg/kg/day |
| Administration: | Infused i.p. at a rate of 0.11 μL/h during 28 days by osmotic mini-pump system |
| Result: | Ameliorated motor coordination and balance dysfunction.
Rescued long-term memory deficit.
Improved the expression of specific synaptic markers.
Reduced the number of huntingtin nuclear inclusions in the striatum and hippocampus. |
IC 50
EP1; EP1: 1.3 μM (Ki); TP: 11.2 μM (Ki); EP3: 17.5 μM (Ki); FP: 61.1 μM (Ki)
References
[1] E. ANN. HALLINAN. N-Substituted dibenzoxazepines as analgesic PGE2 antagonists[J]. Journal of Medicinal Chemistry, 1993, 36 22: 3293-3299. DOI:
10.1021/jm00074a010[2] ANNIKA B. MALMBERG Tony L Y Michael F Rafferty. Antinociceptive effect of spinally delivered prostaglandin E receptor antagonists in the formalin test on the rat[J]. Neuroscience Letters, 1994, 173 1: Pages 193-196. DOI:
10.1016/0304-3940(94)90181-3[3] S.G. KHASAR. Comparison of prostaglandin E1- and prostaglandin E2-induced hyperalgesia in the rat[J]. Neuroscience, 1994, 62 2: Pages 345-350. DOI:
10.1016/0306-4522(94)90369-7[4] E. ANN HALLINAN. Aminoacetyl Moiety as a Potential Surrogate for Diacylhydrazine Group of SC-51089, a Potent PGE2 Antagonist, and Its Analogs[J]. Journal of Medicinal Chemistry, 1996, 39 2: 609-613. DOI:
10.1021/jm950454k
