Nastorazepide hemicalcium  (Synonyms: Z-360 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]}.

Nastorazepide (0.1 μM; 24 h) hemicalcium 可抑制 Gemcitabine (HY-17026) 诱导的 PANC-1 细胞中 HIF-1alpha 基因的表达^[1]。
Nastorazepide hemicalcium 可有效抑制 [³H]CCK-8 与人 CCK-2 受体的特异性结合，K_i 值为 0.47 nM^[2]。
Nastorazepide (10 nM-1 μM) hemicalcium 可降低 OE33 细胞中 Akt 磷酸化水平，并拮抗 G17 对 Akt 磷酸化的影响^[3]。
Nastorazepide (1、10、100 nM) hemicalcium 在 MIA PaCa-2/hCCK2R 细胞中剂量依赖性地抑制 1 nM Gastrin-17 或 1 nM Gastrin-34 诱导的总细胞数量增加^[4]。
Nastorazepide (100 nM；24 小时) hemicalcium 可抑制 Gemcitabine 诱导的 PANC-1 细胞中 VEGFA 基因表达和蛋白水平^[7]。

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Nastorazepide (10-100 mg/kg；口服；每日一次；21 天) hemicalcium 在裸鼠 MiaPaCa2 细胞皮下异种移植模型中以剂量依赖性方式显著抑制肿瘤生长^[2]。
Nastorazepide (3-100 mg/kg；口服；每日一次) hemicalcium 可抑制 C170HM2 小鼠模型中的结直肠癌肝转移，提高MGLVA1 腹水小鼠模型中的生存率，并在 PAN-1 原位小鼠模型中与 Gemcitabine 联合使用时抑制胰腺肿瘤生长^[3]。
Nastorazepide (100 mg/kg；口服；每日一次；3 周) hemicalcium 通过抑制 Gastrin 诱导的抗凋亡作用来抑制 MIA PaCa-2 小鼠的肿瘤生长^[4]。
Nastorazepide (30-300 mg/kg；口服；在癌症疼痛模型中从第 7 天开始持续到第 21 天) hemicalcium 可以抑制Formalin 诱发的疼痛模型中的晚期伤害性反应，并在癌症疼痛模型中产生抗痛觉异常作用^[5]。
Nastorazepide (100 mg/kg；口服；每日一次；从第 7 天到第 14 天) hemicalcium 在癌症诱发的疼痛小鼠模型中通过抑制 IL-1β 的产生来阻止 ephrin B1 基因表达的上调和 NR2B 的磷酸化^[6]。

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

540.66

Z-360 hemicalcium

C₂₉H₃₆N₄O₅.1/2Ca

343326-69-2

Room temperature in continental US; may vary elsewhere.

Please store the product under the recommended conditions in the Certificate of Analysis.

• [1]. Kato H, et al. CCK-2/gastrin receptor signaling pathway is significant for gemcitabine-induced gene expression of VEGF in pancreatic carcinoma cells. Life Sci. 2011 Oct 24;89(17-18):603-8.  [Content Brief]

  [2]. Kawasaki D, et al. Effect of Z-360, a novel orally active CCK-2/gastrin receptor antagonist on tumor growth in human pancreatic adenocarcinoma cell lines in vivo and mode of action determinations in vitro. Cancer Chemother Pharmacol. 2008 Apr;61(5):883-92.  [Content Brief]

  [3]. Grabowska AM, et al. Pre-clinical evaluation of a new orally-active CCK-2R antagonist, Z-360, in gastrointestinal cancer models. Regul Pept. 2008 Feb 7;146(1-3):46-57.  [Content Brief]

  [4]. Shiomi Y, et al. Z-360 Suppresses Tumor Growth in MIA PaCa-2-bearing Mice via Inhibition of Gastrin-induced Anti-Apoptotic Effects. Anticancer Res. 2017 Aug;37(8):4127-4137.  [Content Brief]

  [5]. Yoshinaga K, et al. Pharmacological evaluation of analgesic effects of the cholecystokinin2 receptor antagonist Z-360 in mouse models of formalin- and cancer-induced pain. Biol Pharm Bull. 2010;33(2):244-8.  [Content Brief]

  [6]. Orikawa Y, et al. Z-360, a novel therapeutic agent for pancreatic cancer, prevents up-regulation of ephrin B1 gene expression and phosphorylation of NR2B via suppression of interleukin-1 β production in a cancer-induced pain model in mice. Mol Pain. 2010 Oct 28;6:72.  [Content Brief]

  [7]. Kobayashi N, et al. Z-360, a novel cholecystokinin-2/gastrin receptor antagonist, inhibits gemcitabine-induced expression of the vascular endothelial growth factor gene in human pancreatic cancer cells. Biol Pharm Bull. 2010;33(2):216-22.  [Content Brief]