Nastorazepide (hemicalcium)

Nastorazepide (Z-360) hemicalcium is an orally active 1,5-benzodiazepine derivative and gastrin/CCK-2 receptor antagonist. Nastorazepide hemicalcium inhibits the specific binding of [³H]CCK-8 to the human CCK-2 receptor with a K_i value of 0.47 nM. Nastorazepide hemicalcium inhibits IL-1β, ephrin B1, VEGF, and HIF-1alpha, reduces Akt and NR2B phosphorylation. Nastorazepide hemicalcium has antitumor activity against pancreatic cancer. Nastorazepide hemicalcium inhibits colorectal cancer liver metastasis and relieves pain^{[1][2][3][4][5][6][7]}. In Vitro:Nastorazepide (0.1 μM; 24 h) hemicalcium suppresses Gemcitabine (HY-17026)-induced expression of HIF-1alpha genes in PANC-1 cells^[1].
Nastorazepide hemicalcium potently inhibits specific binding of [³H]CCK-8 to the human CCK-2 receptor, with a K_i value of 0.47 nM^[2].
Nastorazepide (10 nM-1 μM) hemicalcium reduces basal Akt phosphorylation and antagonises the effect of G17 on Akt phosphorylation in OE33 cells^[3].
Nastorazepide (1, 10, 100 nM) hemicalcium dose-dependently inhibits the increase in total cell number induced by 1 nM Gastrin-17 or 1 nM Gastrin-34 in MIA PaCa-2/hCCK2R cells^[4].
Nastorazepide (100 nM; 24 h) hemicalcium suppresses Gemcitabine-induced VEGFA gene expression and protein levels in PANC-1 cells^[7].
In Vivo:Nastorazepide (10-100 mg/kg; p.o.; once daily; 21 days) hemicalcium 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) hemicalcium 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) hemicalcium 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) hemicalcium 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) hemicalcium 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].