Clobenpropit dihydrobromide

SKU: orb1220145

Description

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.

Key Properties

• CAS Number: 145231-35-2
• MW: 470.7
• Purity: >98% (HPLC)
• Formula: C₁₄H₁₉Br₂ClN₄S
• SMILES: Br.Br.Clc1ccc(CNC(=N)SCCCc2cnc[nH]2)cc1
• Target: Histamine Receptor
• Solubility: In Vitro: DMSO : 125 mg/mL (265.59 mM)

Bioactivity

• In Vivo:
  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 xenograft. Dosage: 20 μM per kilogram. Administration: 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).
• In Vitro:
  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).

Storage & Handling

• Storage: Storage temperature: -20°C. Stability: ≥ 2 years
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Quick Database Links

Gene Symbol

Histamine Receptor