MEN11467 is a novel, orally available, potent and selective peptidomimetic tachykinin NK 1 receptor antagonist for the study of acute colon cancer.

Store at -20℃ for one year（Powder）；Store at 2-4℃ for two weeks；Store at -20℃ for six months after dissolution.

NK1 receptors:9.4 (pKi), [Sar9]SP-induced 35SO4 output:0.3 μM

MEN11467 potently inhibits the binding of [3H] substance P (SP) to tachykinin NK1 receptors in the IM9 lymphoblastoid cell line (pKi=9.4±0.1). It is highly specific for human tachykinin NK1 receptors, exhibiting negligible effects (pKi<6) on the binding of specific ligands to tachykinin NK2 or NK3 receptors and to a panel of 30 receptors ion channels unrelated to tachykinin receptors. In saturation binding experiments, the antagonism exerted by MEN11467 at tachykinin NK1 receptors is insurmountable, significantly reducing both KD and Bmax of SP in a concentration-dependent manner (0.3-10 nM). In the guinea-pig isolated ileum, MEN11467 (0.03-1 nM) produces a nonparallel rightward shift of the concentration-response curve to SP methylester with a concomitant reduction of the Emax to the agonist (pKB=10.7±0.1). Furthermore, the antagonist activity of MEN11467 is hardly reversible despite prolonged washout[1].
The pseudopeptide tachykinin NK1 receptor antagonist, MEN11467, is used to study tachykininergic involvement in antigen-induced mucus secretion in ferret trachea in vitro. MEN11467 (1 nM-10 μM) inhibits [Sar9]SP-induced 35SO4 output in a concentration-dependent manner with an approximate IC50 of 0.3  μM[3].

MEN11467 produces a long-lasting (>2-3 h) dose-dependent antagonism of bronchoconstriction induced by the selective tachykinin NK1 receptor agonist, [Sar9, Met(O2)11]SP, in anaesthetized guinea-pigs (ID50s=29±5, 31±12, and 670±270 μg/kg after intravenous, intranasal, and intraduodenal administration, respectively). This effect is observed without affecting bronchoconstriction induced by methacholine. Following oral administration, MEN11467 produces a dose-dependent inhibition of plasma protein extravasation induced in guinea-pig bronchi by [Sar9, Met(O2)11] (ID50= 6.7±2 mg/kg) or by antigen challenge in sensitized animals (ID50=1.3 mg/kg). Upon intravenous administration, MEN11467 weakly inhibits the GR 73632-induced foot-tapping behavior in gerbils (ED50=2.96±2 mg/kg), indicating a poor ability to block central tachykinin NK1 receptors[1].
Treatment with MEN11467 (1 mmol/kg twice weekly for 2 weeks) results in a temporary growth arrest of the U373 MG xenograft that lasts for about 10 days until the last MEN11467 administration (TVI%=56). Thereafter, the tumor starts to regrow. MEN11467’s anti-tumor activity is partially reverted by the simultaneous administration of an equimolar dose of exogenous substance P (SP), suggesting the specificity of tachykinin NK1 receptor activation in glioma growth. Prolonged subcutaneous treatment with a higher MEN11467 dose (1.7 mmol/kg at five times a week for 6 weeks) completely inhibits the growth of the U373 MG tumor for the entire length of the experiment, even following administration of a low exogenous SP dose. After 6 weeks, the tumor mass is not increased compared to the untreated control with TVI%=96%[2].