| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| Targets |
Otaplimastat targets matrix metalloproteinases (MMPs) and NMDA receptors. As an MMP inhibitor, it reduces blood-brain barrier disruption, cerebral edema, and neuronal damage. By competitively blocking NMDA receptor-mediated excitotoxicity, it provides additional neuroprotection. Its antioxidant activity further contributes to its neuroprotective effects.
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| ln Vitro |
In a competitive way, otaplimastat (87.5-350 μM; 20 min) shields neuronal cells against NMDA-induced cell death[1]. In primary cultured neurons, otaplimastat (350 μM) decreases Ca2+ influx after NMDA receptor activation[1]. Reactive oxygen species generation and H2O2-induced cell death are greatly suppressed by otaplimastat (200–200 μM; pretreated for 4 hours)[2].
In vitro, Otaplimastat acts as a matrix metalloproteinase (MMP) inhibitor and competitively blocks NMDA receptor-mediated excitotoxicity. It also has antioxidant activity. Its in vitro activity is assessed by measuring its effects on MMP activity, NMDA receptor-mediated calcium influx, and oxidative stress in neuronal cell cultures. |
| ln Vivo |
In the occlusion model of MCA, otaplimastat (10–20 mg/kg; ip 30 min before occlusion and 1 h after reperfusion) reduces ischemic neuronal death[1]. Otaplimastat (5–10 mg/kg; intraperitoneally; i.p. daily for 10 days) reduces impairment of motor function caused by stroke[2].
In vivo activity of Otaplimastat has been demonstrated in animal stroke models, where it reduces edema and intracerebral hemorrhage induced by recombinant tissue plasminogen activator (rtPA). It enhances recovery and limits brain injury by reducing blood-brain barrier disruption, cerebral edema, and neuronal damage. Its neuroprotective activity supports its development for acute ischemic stroke. |
| Enzyme Assay |
The in vitro enzyme assay for Otaplimastat involves measuring its inhibitory activity against matrix metalloproteinases (MMPs) using purified MMP enzymes and fluorogenic substrates. These assays measure the reduction in MMP-mediated cleavage of substrates in the presence of the compound. The compound's potency as an MMP inhibitor is determined by assessing its IC50 against various MMP isoforms.
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| Cell Assay |
In vitro cellular assays for Otaplimastat are performed using neuronal cell cultures exposed to excitotoxic or oxidative stress. These assays measure the compound's ability to block NMDA receptor-mediated excitotoxicity, reduce oxidative stress, and protect neurons from damage. The compound's neuroprotective activity is demonstrated by its ability to increase cell viability and reduce markers of neuronal injury.
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| Animal Protocol |
Animal/Disease Models: Male Wistar rats (280-310 g, 9 weeks) were induced transient middle cerebral artery (MCA) occlusion[1]
Doses: 10, 20 mg/kg Route of Administration: Ip before 30 min and after an hour of the MCA-occlusion operation Experimental Results: Dramatically decreased infarct volume. Improved spatial learning and memory impairments. In vivo animal studies for Otaplimastat are conducted in rodent models of ischemic stroke, such as middle cerebral artery occlusion (MCAO) models. These studies typically involve administration of the compound, followed by assessment of infarct volume, edema, hemorrhage, and neurological function. The compound's ability to reduce rtPA-induced hemorrhage and enhance recovery is evaluated. |
| ADME/Pharmacokinetics |
Pharmacokinetic properties of Otaplimastat are characterized by its ability to reach the brain and exert neuroprotective effects. As a compound developed for acute ischemic stroke, it is designed for systemic administration and has favorable ADME properties. Its pharmacokinetic profile supports its use as an adjunct to thrombolytic therapy.
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| Toxicity/Toxicokinetics |
Toxicology studies of Otaplimastat have been conducted to evaluate its safety profile as a neuroprotective agent. These studies include acute and repeat-dose toxicity assessments in preclinical species, as well as genotoxicity and safety pharmacology evaluations. As an MMP inhibitor and NMDA receptor antagonist, its toxicology profile includes effects on the central nervous system and vascular function.
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| References |
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| Additional Infomation |
SP-8203 has been used in trials for the treatment of ischemic stroke.
Otaplimastat (SP-8203) is a matrix metalloproteinase (MMP) inhibitor with antioxidant and neuroprotective activity, primarily developed for the treatment of acute ischemic stroke as an adjunct to thrombolytic therapy. It competitively blocks NMDA receptor-mediated excitotoxicity and inhibits the matrix metalloprotease pathway, reducing blood-brain barrier disruption, cerebral edema, and neuronal damage. |
| Molecular Formula |
C28H34N6O5
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|---|---|
| Molecular Weight |
534.61
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| Exact Mass |
534.259
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| CAS # |
1176758-04-5
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| PubChem CID |
44229378
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| Appearance |
Off-white to light yellow solid powder
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| Density |
1.3±0.1 g/cm3
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| Index of Refraction |
1.589
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| LogP |
1.76
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
13
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| Heavy Atom Count |
39
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| Complexity |
913
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
SJZBPVOSFYUHFV-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C28H34N6O5/c1-20(35)32(17-9-19-34-26(37)22-11-3-5-13-24(22)31-28(34)39)16-7-6-14-29-15-8-18-33-25(36)21-10-2-4-12-23(21)30-27(33)38/h2-5,10-13,29H,6-9,14-19H2,1H3,(H,30,38)(H,31,39)
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| Chemical Name |
N-[3-(2,4-dioxo-1H-quinazolin-3-yl)propyl]-N-[4-[3-(2,4-dioxo-1H-quinazolin-3-yl)propylamino]butyl]acetamide
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| Synonyms |
SP8203 SP-8203Otaplimastat
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~100 mg/mL (~187.05 mM)
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.8705 mL | 9.3526 mL | 18.7052 mL | |
| 5 mM | 0.3741 mL | 1.8705 mL | 3.7410 mL | |
| 10 mM | 0.1871 mL | 0.9353 mL | 1.8705 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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