NKP608

NKP608 is a non-peptidic derivative of 4-aminopiperidine, a highly selective, orally active, neurokinin-1 (NK₁) receptor antagonist with IC₅₀ of 2.6 nM. NKP608 is active both in vitro and in vivo, showing extremely low affinity for NK₂, NK₃ receptors. NKP608 exerts its effects by blocking the NK₁ receptor, regulate cell proliferation and apoptosis, affect neurotransmitter functions and gastric mucosal repair mechanisms, and suppress the Wnt/β-catenin pathway in antitumor research. NKP608 is applicable to research related to various diseases, including cough, anxiety disorders, depression, gastric mucosal injury, and colorectal cancer^{[1][2][3][4][5][6][7]}. In Vitro:NKP608 binds to human recombinant NK₁ receptor with a pK_i of 8.96, and shows lower affinity for human recombinant NK₂ (pK_i: 6.1) and NK₃ (pK_i: 6.25) receptors^[1].
NKP608 binds to NK₁ receptor in bovine retina (IC₅₀: 2.6 nM), gerbil midbrain (IC₅₀: 13 nM) and rat striatum (IC₅₀: 27 nM), and exhibits low affinity for NK₂ receptor in bovine bladder (IC₅₀: 2100 nM) and NK₃ receptor in gerbil cortex (IC₅₀: 1500 nM)^[5].
NKP608 (1 μM; 1 h) causes a 20-fold shift in the EC₅₀ of substance P-induced inositol phosphate synthesis in rat cloned NK₁ receptor-expressing CHO cells, and inhibits substance increase in acidification rate in rat NK₁ receptor-expressing CHO cells^[3].
NKP608 (0.001-100 μM; 72 h) inhibits proliferation of human colorectal cancer HCT116 cells in a concentration-dependent manner^[7].
NKP608 (10 μM; 24 h) inhibits migration and invasion of human colorectal cancer HCT116 cells.NKP608 induces apoptosis of human colorectal cancer HCT116 cells, downregulates the expression of Bcl-2, and upregulates the expression of Bax and Active-Caspase-3. NKP608 reduces the expression of Wnt-3a, β-catenin, Cyclin D1 and VEGF, and induces the expression of E-Cadherin in human colorectal cancer HCT116 cells^[7]. In Vivo:NKP608 (0.03, 0.3, 1 mg/kg; p.o.; once; 2 h prior to challenge) significantly reduces citric acid-induced cough in Dunkin Hartley guinea pigs^[1].
NKP608 (0.003, 0.03, 0.3 mg/kg; p.o.; once; 90 min prior to test) exerts anxiolytic-like effects in male spontaneously hypertensive rats (SHR) in the open field test and partial anxiolytic-like effects in male Lewis rats in the elevated plus-maze (EPM) test^[2].
NKP608 (0.2 mg/kg; i.v.; once; immediately prior to agonist challenge) potently inhibits GR73632 (HY-P1192)-induced foot drumming in Mongolian gerbils^[3].
NKP608 (0.01, 0.1, 0.3 mg/kg; p.o.; once; 2 h prior to test) increases social investigation time in Mongolian gerbils, showing robust anxiolytic effects^[4].
NKP608 (0.03-3 mg/kg; p.o.; once; 2, 5 or 24 h prior to agonist administration) dose-dependently inhibits SPOMe-induced hind foot thumping in Mongolian gerbils with ID₅₀ values of 0.23 mg/kg (2 h), 0.15 mg/kg (5 h) and 0.38 mg/kg (24 h), respectively^[5].
NKP608 (0.01-1 mg/kg; p.o.; once; 90 min prior to test) specifically increases active social interaction time in Sprague-Dawley rats in a highly illuminated unfamiliar arena^[5].
NKP608 (0.03-3 mg/kg; p.o.; once; 90 min prior to test) increases social exploration time of intruder rats towards resident rats in Sprague-Dawley rats^[5].
NKP608 (1 mg/kg; i.g.; once daily; for 8 consecutive days) delays gastric cryoulcer healing and decreases the number of Ki-67-positive epithelial cells in the ulcer margin in both wild-type and COX-2^-/- mice^[6].