Recently, a series of relatively simple compounds were found to be high-affinity ligands and functional antagonists for the human IP (prostacyclin) receptor.
CAS：221529-58-4
分子式：C19H23N3O
分子量：309.4
纯度：98%
存储：Store at -20°C

Background:

RO1138452 is a potent and selective IP (prostacyclin) receptor antagonist. RO1138452 displays high affinity for IP receptors. In human platelets, pKi is 9.3±0.1; in a recombinant IP receptor system, pKi is 8.7±0.06.

RO1138452 is IP receptor antagonist. The pIC50 values of RO1138452 in attenuating cAMP accumulation is 7.0±0.07. Functional antagonism of RO1138452 is studied by measuring inhibition of carbaprostacyclin-induced cAMP accumulation in CHO-K1 cells stably expressing the human IP receptor. The antagonist affinity (pKi) of RO1138452 is 9.0±0.06. Selectivity profiles for RO1138452 are determined via a panel of receptor binding and enzyme assays. RO1138452 displays affinity at imidazoline2 (I2) (8.3) and platelet activating factor (PAF) (7.9) receptors[1]. RO1138452 (10 pM-10 μM) added to cells concurrently with a fixed concentration of Taprostene (1 μM) prevents, in a concentration-dependent manner, the inhibition of CXCL9 and CXCL10 release, with p[A]50 (molar) values of -8.73±0.11 and -8.47±0.16 (p>0.05), respectively[2].

RO1138452 is a potent and selective antagonist for both human and rat IP receptors and that is possesses analgesic and anti-inflammatory potential. RO1138452 (1-10?mg/kg, i.v.) significantly reduces acetic acid-induced abdominal constrictions. RO1138452 (3-100?mg/kg, p.o.) significantly reduces carrageenan-induced mechanical hyperalgesia and edema formation. One?hour after administration of RO1138452 (5?mg/kg, i.v.) to rats, the total plasma concentration is 0.189 ?μg/mL, whereas the free plasma concentrations is calculated to be 0.009?μg/mL (28 nM)[1].

参考文献:
[1]. Bley KR, et al. RO1138452 and RO3244794: characterization of structurally distinct, potent and selective IP (prostacyclin) receptor antagonists. Br J Pharmacol. 2006 Feb;147(3):335-45.
[2]. Ayer LM, et al. 4,5-Dihydro-1H-imidazol-2-yl)-[4-(4-isopropoxy-benzyl)-phenyl]-amine (RO1138452) is a selective, pseudo-irreversible orthosteric antagonist at the prostacyclin (IP)-receptor expressed by human airway epithelial cells: IP-receptor-mediated inhibition of CXCL9 and CXCL10 release. J Pharmacol Exp Ther. 2008 Feb;324(2):815-26.