Otaplimastat

Names

[ Name ]:
Otaplimastat

[Synonym ]:
SP-8203
N-[3-(2,4-Dioxo-1,4-dihydro-3(2H)-quinazolinyl)propyl]-N-(4-{[3-(2,4-dioxo-1,4-dihydro-3(2H)-quinazolinyl)propyl]amino}butyl)acetamide
UYE03B60KA
Acetamide, N-[3-(1,4-dihydro-2,4-dioxo-3(2H)-quinazolinyl)propyl]-N-[4-[[3-(1,4-dihydro-2,4-dioxo-3(2H)-quinazolinyl)propyl]amino]butyl]-

Biological Activity

[Description]:

Otaplimastat (SP-8203), a matrix metalloproteinase (MMP) inhibitor, blocks N-methyl-D-aspartate (NMDA) receptor-mediated excitotoxicity in a competitive manner. Otaplimastat also exhibits anti-oxidant activity. Otaplimastat can be used for the research of brain ischemic injury[1][2][3].

[Related Catalog]:

Signaling Pathways >> Neuronal Signaling >> iGluR

Signaling Pathways >> Metabolic Enzyme/Protease >> MMP

Research Areas >> Neurological Disease

Signaling Pathways >> Membrane Transporter/Ion Channel >> iGluR

[Target]

MMP

NMDA

[In Vitro]

Otaplimastat (87.5-350 μM; 20 min) protects neuronal cells against NMDA-induced cell death in a competitive manner[1]. Otaplimastat (350 μM) inhibits Ca2+ influx following activation of NMDA receptors in primary cultured neuron[1]. Otaplimastat (2-200 μM; pretreated for 4 h) significantly suppresses H2O2-induced cell death and reactive oxygen species production[2].

[In Vivo]

Otaplimastat (10-20 mg/kg; i.p. 30 min before occlusion and 1 h after reperfusion) prevents ischemic neuronal death in the occlusion model of MCA[1]. Otaplimastat (5-10 mg/kg; i.p. daily for 10 days) attenuates impairment of stroke-induced motor function[2]. Animal Model: Male Wistar rats (280-310 g, 9 weeks) were induced transient middle cerebral artery (MCA) occlusion[1] Dosage: 10, 20 mg/kg Administration: I.p. before 30 min and after an hour of the MCA-occlusion operation Result: Significantly reduced infarct volume. Improved spatial learning and memory impairments.

[References]

[1]. Noh SJ, et, al. SP-8203 shows neuroprotective effects and improves cognitive impairment in ischemic brain injury through NMDA receptor. Pharmacol Biochem Behav. 2011 Nov;100(1):73-80.

[2]. Noh SJ, et, al. SP-8203 reduces oxidative stress via SOD activity and behavioral deficit in cerebral ischemia. Pharmacol Biochem Behav. 2011 Mar;98(1):150-4.

[3]. Kim JS, et, al. Safety and Efficacy of Otaplimastat in Patients with Acute Ischemic Stroke Requiring tPA (SAFE-TPA): A Multicenter, Randomized, Double-Blind, Placebo-Controlled Phase 2 Study. Ann Neurol. 2020 Feb;87(2):233-245.

Chemical & Physical Properties

[ Density]:
1.3±0.1 g/cm3

[ Molecular Formula ]:
C₂₈H₃₄N₆O₅

[ Molecular Weight ]:
534.607

[ Exact Mass ]:
534.259094

[ LogP ]:
1.76

[ Index of Refraction ]:
1.589

Related Compounds

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