MRE-269-d6

MRE-269-d6 is intended for use as an internal standard for the quantification of MRE-269 (Cay-10010412) by GC- or LC-MS. MRE-269 is an IP receptor agonist and an active metabolite of NS 304 (Cay-10010411). It is formed from NS 304 primarily via carboxylesterase 1 (CES1) in human liver microsomes and via CES2 in human intestinal microsomes. It binds to the IP receptor (Ki = 20 nM) and increases cAMP levels in human pulmonary artery smooth muscle cells (PASMCs) in a concentration-dependent manner. It is selective for the IP receptor over the DP receptor (IC50 = 2. µM), EP1, EP2, EP3, and EP4 receptors (IC50s = >10, 5. >10, and 4. µM, respectively), FP receptor (IC50 = >10 µM), and TP receptor (IC50 = >10 µM). Due to its selectivity for IP over EP3 receptors, MRE-269 induces vasodilation equally in both large and small isolated rat pulmonary arteries in a concentration-dependent manner. It also inhibits ADP-induced platelet aggregation in isolated human and rat platelet-rich plasma (IC50s = 0. and 10 µM, respectively). MRE-269 reduces PDGF-induced proliferation of primary PASMCs derived from patients with chronic thromboembolic pulmonary hypertension (CTEPH). InChI: InChI=1S/C25H29N3O3/c1-19(2)28(15-9-10-16-31-18-23(29)30)22-17-26-24(20-11-5-3-6-12-20)25(27-22)21-13-7-4-8-14-21/h3-8,11-14,17,19H,9-10,15-16,18H2,1-2H3,(H,29,30)/i1D3,2D3 InChIKey: OJQMKCBWYCWFPU-WFGJKAKNSA-N SMILES: OC(COCCCCN(C(C([2H])([2H])[2H])C([2H])([2H])[2H])C1=CN=C(C(C2=CC=CC=C2)=N1)C3=CC=CC=C3)=O