| Description | Camicinal hydrochloride (GSK962040 hydrochloride) is a selective agonist of motilin receptor (pEC50 = 7.9). |
| In vitro | Camicinal hydrochloride 激活了犬的胃动素受体（pEC50 5.79；内在活性0.72，与[Nle13]-胃动素相比）[1]。由于其初始IC50值在CYP3A4上显著高于首选的10 μM门槛，因此选择了Camicinal hydrochloride [2]。此化合物在其他受体（包括ghrelin）、离子通道和酶上均无明显活性。在兔胃窦中，Camicinal hydrochloride（300 nmol/L至10 μmol/L）显著加强了由胆碱能介导的收缩幅度，3 μmol/L时最大增至248 ± 47%。胃动素、红霉素和Camicinal hydrochloride的pEC50值分别为10.4 ± 0.01（n = 770）、7.3 ± 0.29（n = 4）和7.9 ± 0.09（n = 17）[4]。 |
| In vivo | Camicinal hydrochloride诱导的短暂收缩具有剂量依赖性，持续时间分别为48分钟和173分钟（对于3 mg/kg和6 mg/kg剂量），这是由平均血浆浓度大于1.14 μmol/L驱动的。Camicinal hydrochloride的效果消退后，移行性肌动复合体（MMC）活动恢复。3 mg/kg剂量的Camicinal hydrochloride并未影响MMC恢复，但在6 mg/kg时，MMC在给药后253分钟恢复，而生理盐水组则为101分钟（每组n=5）[1]。Camicinal hydrochloride的口服生物利用度（Fpo）为48（13%）。与[Nle13]motilin的短暂效应相比（T1/2）11.4（1.5分钟，在0.3 μM），Camicinal hydrochloride显示出长效（T1/2）46.9（5.0分钟，在3 μM）[2]。5 mg/kg剂量的Camicinal hydrochloride在给药后2小时内也显著增加了总粪便重量（21.2 ± 4.5克；P < 0.05）[4]。此外，Camicinal hydrochloride在胃窦显著促进胆碱能活动，但在胃底部和小肠的活动则较低[4]。 |
| Target activity | Motilin receptor:7.9 (pEC50) |
| Synonyms | GSK962040 hydrochloride |
| molecular weight | 461.02 |
| Molecular formula | C25H34ClFN4O |
| CAS | 923565-22-4 |
| Storage | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice. |
| Solubility | DMSO: 95 mg/mL (206.06 mM), Sonication is recommended. H2O: 95 mg/mL (206.06 mM), Sonication is recommended. |
| References | 1. Sanger, G.J., et al., GSK962040: a small molecule, selective motilin receptor agonist, effective as a stimulant of human and rabbit gastrointestinal motility. Neurogastroenterol Motil, 2009. 21(6): p. 657-64, e30-1. 2. Leming, S., et al., GSK962040: a small molecule motilin receptor agonist which increases gastrointestinal motility in conscious dogs. Neurogastroenterol Motil, 2011. 23(10): p. 958-e410. 3. Westaway, S.M., et al., Discovery of N-(3-fluorophenyl)-1-[(4-([(3S)-3-methyl-1-piperazinyl]methyl)phenyl)acetyl]-4-pi peridinamine (GSK962040), the first small molecule motilin receptor agonist clinical candidate. J Med Chem, 2009. 52(4): p. 1180-9. 4. Broad, J., et al., Regional- and agonist-dependent facilitation of human neurogastrointestinal functions by motilin receptor agonists. Br J Pharmacol, 2012. 167(4): p. 763-74. |