HAMI 3379

HAMI 3379 is a potent and selective Cysteinyl leukotriene (CysLT2) receptor antagonist[1]. HAMI 3379 has a protective effect on acute and subacute ischemic brain injury, and attenuates microglia-related inflammation[2].

Research Areas >> Cardiovascular Disease

Signaling Pathways >> GPCR/G Protein >> Leukotriene Receptor

Research Areas >> Inflammation/Immunology

Research Areas >> Neurological Disease

CysLT2

In a CysLT2 receptor reporter cell line, HAMI 3379 antagonizes leukotriene D4- (LTD4-) and leukotriene C4- (LTC4-) induced intracellular calcium mobilization with IC50 values of 3.8 nM and 4.4 nM, respectively. In contrast, HAMI 3379 exhibits very low potency on a recombinant CysLT1 receptor cell line (IC50>10000 nM)[1].

HAMI 3379 (ip; 0.025-0.4 mg/kg; 24 hours) attenuates the acute brain injury 24 hours after middle cerebral artery occlusion (MCAO) with effective doses of 0.1-0.4 mg/kg and a therapeutic window of ∼1 hour. It attenuates the neurological deficits, and reduces infarct volume, brain edema, and neuronal loss and degeneration 24 and 72 hours after MCAO[2]. HAMI 3379 (infused into the aortic cannula at a rate of 1% of the total flow rate; 0.01, 0.1, 1 μM; 20 min) concentration-dependently inhibits and reverses the LTC4-induced perfusion pressure increase and contractility decrease[1]. Animal Model: Male Sprague-Dawley rats (250-300 g) after MCAO[2] Dosage: 0.025, 0.05, 0.1, 0.2, 0.4 mg/kg Administration: IP; 24 hours Result: Attenuated the acute brain injury 24 hours after MCAO with effective doses of 0.1-0.4 mg/kg and a therapeutic window of ∼1 hour.

[1]. Wunder F, et al. Pharmacological characterization of the first potent and selective antagonist at the cysteinyl leukotriene 2 (CysLT(2)) receptor. Br J Pharmacol. 2010 May;160(2):399-409.

[2]. Zhang XY, et al. HAMI 3379, a CysLT2 receptor antagonist, attenuates ischemia-like neuronal injury by inhibiting microglial activation. J Pharmacol Exp Ther. 2013 Aug;346(2):328-41.