MEN10376

MEN10376 is a peptide neurokinin-2 (NK2) receptor antagonist. It inhibits contractions induced by neurokinin A (NKA) in endothelium-deprived isolated rabbit pulmonary artery (pA2 = 8.08), which is endogenously enriched in NK2 receptors. It is selective for NK2 receptors in isolated rabbit pulmonary artery over NK2 receptors in isolated hamster trachea (pA2 = 5.64 using NKA as an agonist) and NK1 receptors in isolated guinea pig ileum (pA2 = 5.66 using substance P methyl ester as an agonist), tissues that highly express these respective receptors, as well as NK3 receptors in isolated guinea pig cerebral cortex membranes (Ki = >10 µM). In vivo, MEN10376 (1 and 3 µmol/kg) inhibits increases in bladder motility induced by the NK2 receptor agonist [beta-Ala8]-NKA(4-10) in anesthetized rats, as well as [beta-Ala8]-NKA(4-10)-induced increases in bronchoconstriction in anesthetized guinea pigs.Formal Name: L-alpha-aspartyl-L-tyrosyl-D-tryptophyl-L-valyl-D-tryptophyl-D-tryptophyl-L-lysinamide. CAS Number: 135306-85-3. Synonyms: DYWVWWK-NH2, Asp-Tyr-Trp-Val-Trp-Trp-Lys-NH2. Molecular Formula: C57H68N12O10. Formula Weight: 1081.2. Purity: >98%. Formulation: (Request formulation change), A crystalline solid. Solubility: DMF: 30 mg/ml, DMSO: 30 mg/ml, DMSO:PBS (pH 7.2) (1:5): 0.16 mg/ml. lambdamax: 222 nm. SMILES: OC(C[C@H](N)C(N[C@@H](CC1=CC=C(O)C=C1)C(N[C@H](CC2=CNC3=C2C=CC=C3)C(N[C@@H](C(C)C)C(N[C@H](CC4=CNC5=C4C=CC=C5)C(N[C@H](CC6=CNC7=C6C=CC=C7)C(N[C@@H](CCCCN)C(N)=O)=O)=O)=O)=O)=O)=O)=O. InChi Code: InChI=1S/C57H68N12O10/c1-31(2)50(69-56(78)48(26-35-30-63-43-16-8-5-13-39(35)43)67-53(75)45(23-32-18-20-36(70)21-19-32)65-52(74)40(59)27-49(71)72)57(79)68-47(25-34-29-62-42-15-7-4-12-38(34)42)55(77)66-46(24-33-28-61-41-14-6-3-11-37(33)41)54(76)64-44(51(60)73)17-9-10-22-58/h3-8,11-16,18-21,28-31,40,44-48,50,61-63,70H,9-10,17,22-27,58-59H2,1-2H3,(H2,60,73)(H,64,76)(H,65,74)(H,66,77)(H,67,75)(H,68,79)(H,69,78)(H,71,72)/t40-,44-,45-,46+,47+,48+,50-/m0/s1. InChi Key: QQHOFZNACVKNHK-SXVLBCBNSA-N.