Nastorazepide

Nastorazepide (Z-360) is an orally active 1,5-benzodiazepine derivative and gastrin/CCK-2 receptor antagonist. Nastorazepide inhibits the specific binding of [³H]CCK-8 to the human CCK-2 receptor with a K_i value of 0.47 nM. Nastorazepide inhibits IL-1β, ephrin B1, VEGF, and HIF-1alpha, reduces Akt and NR2B phosphorylation. Nastorazepide has antitumor activity against pancreatic cancer. Nastorazepide inhibits colorectal cancer liver metastasis and relieves pain^{[1][2][3][4][5][6][7]}. In Vitro:Nastorazepide (Z-360) is an orally active 1,5-benzodiazepine derivative and gastrin/CCK-2 receptor antagonist. Nastorazepide inhibits the specific binding of [³H]CCK-8 to the human CCK-2 receptor with a K_i value of 0.47 nM. Nastorazepide inhibits IL-1β, ephrin B1, VEGF, and HIF-1alpha, reduces Akt and NR2B phosphorylation. Nastorazepide has antitumor activity against pancreatic cancer. Nastorazepide inhibits colorectal cancer liver metastasis and relieves pain^{[1][2][3][4][5][6][7]}. In Vivo:Nastorazepide (10-100 mg/kg; p.o.; once daily; 21 days) significantly inhibits tumor growth in a dose-dependent manner in subcutaneous xenograft model of MiaPaCa2 cells in nude mice^[2].
Nastorazepide (3-100 mg/kg; p.o.; once daily) inhibits colorectal cancer liver metastasis in the C170HM2 mouse model, increases survival in the MGLVA1 ascites mouse model, and inhibits pancreatic tumor growth when combined with Gemcitabine in the PAN-1 orthotopic mouse model^[3].
Nastorazepide (100 mg/kg; p.o.; once daily; 3 weeks) suppresses tumor growth in MIA PaCa-2-bearing mice via inhibition of Gastrin-induced anti-apoptotic effects^[4].
Nastorazepide (30-300 mg/kg; p.o.; starting from day 7 and continuing until day 21 in the cancer pain model) can inhibit the late-phase nociceptive responses in the Formalin-induced pain model, produce an anti-allodynic effect in the cancer pain model^[5].
Nastorazepide (100 mg/kg; p.o.; once daily; from day 7 to day 14) prevents up-regulation of ephrin B1 gene expression and phosphorylation of NR2B via suppression of IL-1β production in a cancer-induced pain model in mice^[6].