AL 8810

AL-8810 is a novel prostaglandin F2α analog that acts as a selective antagonist of prostaglandin F2α (FP) receptor.

Prostaglandin receptors are a group of g-protein coupled receptor that exhibited a variety of functions in regulation of blood pressure and renal function; smooth muscle contraction; inhibition of plate aggregation; immune response etc.

AL-8810 has a EC50 of 261 ± 44 nM against FP receptor in the A7r5 rat thoracic aorta smooth muscle cells and a EC50 of 186 ± 63 nM in Swiss mouse 3T3 fibroblasts. In addition, AL-8810 antagonizes the response to 100 nM fluprostenol (Ki = 426 ± 63 nM) in a concentration- dependent manner in A7r5 cells. [1]

In the h-TM cells, AL-8810 antagonizes the (±) fluprostenol-induced PI turn over responses concentration dependently (Ki=2.56 ± 0.62 μm). AL-8810 also antagonizes bimatoprost, travoprost acid, latanoprost acid and travoprost acid. [2] In HCM cells, 1 μm AL-8810 blocks the 85% PGF2-induced MMP-2 secretion and 66% PGF2α-induced activation of ERK1/2. [3]

References:
1.  Griffin BW, Klimko P, Crider JY, Sharif NA. AL-8810: a novel prostaglandin F2 alpha analog with selective antagonist effects at the prostaglandin F2 alpha (FP) receptor. J Pharmacol Exp Ther. 1999 Sep;290(3):1278-84.
2.  Husain S, Jafri F, Crosson CE. Acute effects of PGF2alpha on MMP-2 secretion from human ciliary muscle cells: a PKC- and ERK-dependent process. Invest Ophthalmol Vis Sci. 2005 May;46(5):1706-13.
3.  Sharif NA, Kelly CR, Crider JY. Human trabecular meshwork cell responses induced by bimatoprost, travoprost, unoprostone, and other FP prostaglandin receptor agonist analogues. Invest Ophthalmol Vis Sci. 2003 Feb;44(2):715-21.

AL-8810: a novel prostaglandin F2 alpha analog with selective antagonist effects at the prostaglandin F2 alpha (FP) receptor.[Pubmed:10454504]

J Pharmacol Exp Ther. 1999 Sep;290(3):1278-84.

A novel analog of prostaglandin F(2alpha) [AL-8810; (5Z, 13E)-(9S, 11S,15R)-9,15-dihydroxy-11-fluoro-15-(2-indanyl)-16,17,18,19, 20-pentanor-5,13-prostadienoic acid] has been discovered with uniquely low efficacy (E(max)) at the endogenous prostaglandin F(2alpha) receptors (FP receptors) of A7r5 rat thoracic aorta smooth muscle cells and Swiss mouse 3T3 fibroblasts, as assayed by stimulation of phospholipase C activity. AL-8810 has weak agonist potency (EC(50)) of 261 +/- 44 nM (n = 3) and E(max) = 19% (relative to the full FP receptor agonist cloprostenol) in A7r5 cells and EC(50) of 186 +/- 63 nM (n = 3) and E(max) = 23% in 3T3 fibroblasts. AL-8810 exhibited properties of an apparent competitive antagonist, i.e., produced parallel dextral shifts of the agonist concentration-response curves and no significant suppression of the maximal agonist-induced response, when the potent, selective FP receptor agonist fluprostenol was used. The inhibition parameters of AL-8810 were: pA(2) = 6.68 +/- 0.23 and 6.34 +/- 0.09 (n = 3-4) for A7r5 cells and 3T3 cells, respectively, with Schild slopes ranging from 0.80 to 0.92. AL-8810 concentration-dependently antagonized the response to 100 nM fluprostenol (K(i) = 426 +/- 63 nM; n = 5) in A7r5 cells. However, even at 10 microM concentration, AL-8810 did not significantly inhibit functional responses of TP, DP, EP(2), EP(4), receptor subtypes in various cell lines. AL-8810 also did not antagonize the phospholipase C-coupled V(1)-vasopressin receptor in A7r5 cells. These results suggest that AL-8810 is a unique, selective antagonist at the FP receptor, a heretofore unavailable pharmacological tool that should be valuable for studying FP receptor-mediated functional responses in complex biological systems.