Clobenpropit (dihydrobromide)

Clobenpropit dihydrobromide is a potent histamine H3R antagonist/inverse agonist with a pEC₅₀ of 8.07 for histamine H3LR^[1]. Clobenpropit dihydrobromide acts as partial agonist at histamine H4 receptors (K_i 13 nM). Clobenpropit dihydrobromide also binds to serotonin 5-HT3 receptors (K_i 7.4 nM) and α2A/α2C adrenoceptors (K_i 17.4/7.8 nM)^[2]. Clobenpropit dihydrobromide increases apoptosis^[3]. IC50 & Target: pEC50: 8.07 (histamine H3LR)^[1]
Ki: 13 nM (histamine H4 receptors), 7.4 nM (serotonin 5-HT3 receptors), 17.4/7.8 nM (α2A/α2C adrenoceptors)^[2]
pKi: 9.44±0.04 (human H3LR), 9.75±0.01 (Rat H3LR), 5.2 (histamine H1R), 5.6 (histamine H2R)^[1]. In Vitro: Clobenpropit binds to human H3LR and rat H3LR with pK_is of 9.44±0.04 and 9.75±0.01. Clobenpropit exhibits low affinity for histamine H1R or H2R (pK_is of 5.2 and 5.6, respectively)^[1].
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)^[2].
Clobenpropit is a subunit-selective noncompetitive antagonist at recombinant NMDA receptors (IC₅₀ 1 μM for the NR1/NR2B receptor)^[2].
Clobenpropit (50 μM) and Gemcitabine (5 μM) combination therapy significantly increases apoptosis of Panc-1, MiaPCa-2 and AsPC-1 compared with control^[3]. 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^[3].