246246-19-5 Usage
Uses
AL 8810 is an 11β-fluoro analog of PGF2α which acts as a potent and selective antagonist at the FP receptor. AL 8810 has weak intrinsic agonist activity on FP receptor preparations in the 200-300 nM range, yet it fully antagonizes the activity of the potent FP receptor agonist fluprostenol at this concentration, with EC50 values of approximately 430 nM. AL 8810 fully antagonized the bimatoprost-induced calcium mobilization in Swiss 3T3 fibroblasts at 100 μM, indicating that bimatoprost acts as an FP agonist in this preparation. The Ki for the inhibition of several potent agonists at the cloned human ciliary body FP receptor is in the range of 1-2 μM.
Biological Activity
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]
Biochem/physiol Actions
AL-8810 is a novel prostaglandin F2α analog; selective FP prostanoid receptor antagonist.
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.
Check Digit Verification of cas no
The CAS Registry Mumber 246246-19-5 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 2,4,6,2,4 and 6 respectively; the second part has 2 digits, 1 and 9 respectively.
Calculate Digit Verification of CAS Registry Number 246246-19:
(8*2)+(7*4)+(6*6)+(5*2)+(4*4)+(3*6)+(2*1)+(1*9)=135
135 % 10 = 5
So 246246-19-5 is a valid CAS Registry Number.
InChI:InChI=1/C24H31FO4/c25-21-15-23(27)20(9-3-1-2-4-10-24(28)29)19(21)11-12-22(26)18-13-16-7-5-6-8-17(16)14-18/h1,3,5-8,11-12,18-23,26-27H,2,4,9-10,13-15H2,(H,28,29)/b3-1-,12-11+/t19-,20-,21+,22+,23+/m1/s1
246246-19-5Relevant articles and documents
AL-8810: A novel prostaglandin F(2α) analog with selective antagonist effects at the prostaglandin F(2α) (FP) receptor
Griffin, Brenda W.,Klimko, Peter,Crider, Julie Y.,Sharif, Najam A.
, p. 1278 - 1284 (2007/10/03)
A novel analog of prostaglandin F(2α) [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(2α) 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 (EC50) of 261 ± 44 nM (n = 3) and E(max) = 19% (relative to the full FP receptor agonist cloprostenol) in A7r5 cells and EC50 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: pA2 = 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 μM concentration, AL-8810 did not significantly inhibit functional responses of TP, DP, EP2, EP4, receptor subtypes in various cell lines. AL-8810 also did not antagonize the phospholipase C-coupled V1-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.
