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HAMI3379 is a cysteinyl leukotriene 2 (CysLT2) receptor antagonist (IC50 = 37.9 nM in a radioligand binding assay).1 It is selective for CysLT2 over CysLT1 (IC50 = >30 μM in a radioligand binding assay). HAMI3379 inhibits calcium mobilization induced by leukotriene D4 (LTD4; ） or leukotriene C4 (LTC4; ） in CHO cells expressing human CysLT2 (IC50s = 3.8 and 4.4 nM, respectively). It reverses the LTC4-induced increases in perfusion pressure and decreases in contractility in isolated Langendorff-perfused guinea pig hearts in a concentration-dependent manner. HAMI3379 (0.1 mg/kg) prevents decreases in body weight and neurological deficit scores in a rat model of S. pneumoniae-induced meningitis, as well as reduces infarct volume in a rat model of cerebral ischemia brain injury induced by middle cerebral artery occlusion (MCAO).2,3 It also prevents increases in airway hyperresponsiveness in a mouse model of ovalbumin-induced asthma when administered at a dose of 10 mg/kg.4 | [References]
1. Wunder, F., Tinel, H., Kast, R., et al. Pharmacological characterization of the first potent and selective antagonist at the cysteinyl leukotriene 2 (CysLT2) receptor Br. J. Pharmacol. 160(2),399-409(2010).
2. Yu, S., Chen, X., Li, X., et al. Neuroprotective effects of CysLTR antagonist on Streptococcus pneumoniae?induced meningitis in rats Exp. Ther. Med. 24(1),443(2022).
3. Shi, Q.J., Wang, H., Liu, Z.X., et al. HAMI 3379, a CysLT2R antagonist, dose- and time-dependently attenuates brain injury and inhibits microglial inflammation after focal cerebral ischemia in rats Neuroscience 291,53-69(2015).
4. Trinh, H.K.T., Suh, D.-H., Nguyen, T.V.T., et al. Characterization of cysteinyl leukotriene-related receptors and their interactions in a mouse model of asthma Prostaglandins Leukot. Essent. Fatty Acids 141,17-23(2019). |
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