Clobenpropit dihydrobromide

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

Clobenpropit dihydrobromide 是组胺 H3R 的有效拮抗剂和反向激动剂（组胺 H3LR，pEC50 为 8.07）Clobenpropit 与吉西他滨联合使用可抑制细胞迁移并增加胰腺癌细胞的凋亡。

Clobenpropit dihydrobromide is a potent ?antagonist and inverse agonist of histamine H3R (histamine H3LR,pEC50 of 8.07)Clobenpropit inhibited cell migration and increased apoptosis of pancreatic cancer cells in combination with gemcitabine.?Clobenpropit up-regulated E-cadherin, but down-regulated vimentin and matrix metalloproteinase 9 in real-time polymerase chain reaction.?Clobenpropit inhibited tumor growth (gemcitabine 294 46 mg vs combination 154 54 mg, P = 0.02) and enhanced apoptosis in combination with gemcitabine (control 2.5%, gemcitabine 25.8%, clobenpropit 9.7% and combination 40.9%, P = 0.001) by up-regulation of E-cadherin and down-regulation of Zeb1 in Panc-1 xenograft mouse.

Clobenpropit binds to human H3LR and rat H3LR with pKis of 9.44±0.04 and 9.75±0.01. Clobenpropit exhibits low affinity for histamine H1R or H2R (pKis of 5.2 and 5.6, respectively). Clobenpropit inhibits [3H]-dopamine transport by SH-SY5Y cells in a concentration dependent manner with maximum inhibition 82.7±2.8 % and IC50 490 nM (pIC50 6.31±0.11). Clobenpropit is a subunit-selective noncompetitive antagonist at recombinant NMDA receptors (IC50 1 μM for the NR1/NR2B receptor).Clobenpropit (50 μM) and Gemcitabine (5 μM) combination therapy significantly increases apoptosis of Panc-1, MiaPCa-2 and AsPC-1 compared with control. Apoptosis Analysis Cell Line:Pancreatic cancer cells (Panc-1, MiaPaCa-2 and AsPC-1) Concentration:50 μM Incubation Time:Result:Enhanced apoptotic cell death in combination of Gemcitabine (5 μM).

The combination treatment of Clobenpropit (every other day intraperitoneal injection at 20 μM per kilogram for 40 d) and Gemcitabine (twice-a-week intraperitoneal injection at 125 mg/kg for 40 d) shows significant tumor growth inhibition. Animal Model:Five-week-old male BALB/c nude mice with Panc-1 xenograftDosage:20 μM per kilogramAdministration:Intraperitoneal injection; every other day for 40 days. Gemcitabine (twice-a-week intraperitoneal injection at 125 mg/kg for 40 d) Result:The combination treatment showed significant tumor growth inhibition compared with other treatment groups (control 501±92 mg, Gemcitabine 294±46 mg, Clobenpropit 444±167 mg, and combination 154±54 mg).

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GPCR/G Protein

Histamine Receptor

H3 receptor

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145231-35-2

470.7

C14H19Br2ClN4S

>98% (HPLC)

In Vitro:?DMSO : 125 mg/mL (265.59 mM)

Br.Br.Clc1ccc(CNC(=N)SCCCc2cnc[nH]2)cc1

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(-20℃)

With Ice Pack

≥ 2 years