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| 5mg |
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| Other Sizes |
Purity: ≥98%
| Targets |
Alicapistat targets calpain 1 and calpain 2, two calcium-dependent cysteine proteases that are implicated in various neurodegenerative diseases. Calpains are ubiquitously expressed proteases that are activated by elevated intracellular calcium levels and play roles in cytoskeletal remodeling, cell signaling, and apoptosis. Overactivation of calpains has been implicated in neuronal degeneration through mechanisms such as excitotoxicity and cholinergic neurodegeneration. Calpains contribute to the cleavage of proteins involved in synaptic function and neuronal survival, and their dysregulation is associated with Alzheimer's disease and other neurodegenerative disorders. Alicapistat is a selective inhibitor of calpain 1 and 2. The compound inhibits calpain 1 with an IC50 of 395 nM.
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| ln Vitro |
To achieve pharmacodynamic effects, Alicapistat's CNS osmotic concentration is insufficient [1]. Both calcium 1 (u-) and calcium 2 (m-) are expressed as calcium ions, and u-is necessary for the activation of each calcium ion. Compound 22 (Alicapistat) at 100 nM inhibits synaptic transmission impairments caused by Aβ oligomers in Contact [2]. In hippocampus slice cultures, alicapistat (Compound 22) (385 nM) has demonstrated effectiveness in averting NMDA-induced neurotoxicity and A-induced synaptic dysfunction [2]. In a variety of concentration experiments, aliapistat (9–21 nM) has demonstrated no dose-limiting toxicity (DLT) and has CSF values that fall short of the IC50 for calcium inhibition [3].
Alicapistat demonstrates in vitro activity as a calpain inhibitor. The compound inhibits human calpain 1 with an IC50 of 395 nM. Alicapistat is an orally active, selective inhibitor of human calpains 1 and 2. The compound's selectivity for calpains over other proteases makes it a valuable tool for studying the role of calpains in neurodegenerative diseases. Alicapistat has been investigated for use in Alzheimer's disease research. The compound can reduce the metabolic liability of carbonyl reduction. Detailed cellular activity data, including effects on calpain-mediated protein cleavage and cell survival, are available in the primary literature. |
| ln Vivo |
The majority of the mean venous clearance (CLp) values (0.13-1.04 L/hr.kg) in mice, rats, and dogs were proven by Alicapistat (Compound 22) (intravenous or intravenous; 1-3 mg/kg), however the aforementioned value (1.98 liters/hour.kg) was observed in monkeys. In mice, dogs, and monkeys, the mean growth rate (Vss) ranged from 0.64 to 1.8 L/kg, with mice exhibiting the highest Vss of 3.4 L/kg. Dogs had the longest half-hour elimination life (t1/2) at 1.7 hours, followed by monkeys at 2.3 hours and monkeys at 6.0 hours. Dogs and fortresses have high (>80%) fortress bioavailability (F) values, but monkeys have moderate (14%) values [2].
Alicapistat has been evaluated in vivo for its potential in Alzheimer's disease. The compound is orally active and has been investigated for use in Alzheimer's disease (AD) research. In preclinical studies, Alicapistat has been evaluated for its ability to inhibit calpain activity and reduce neuronal degeneration. Calpains 1 and 2 are believed to contribute to neuronal degeneration through mechanisms such as excitotoxicity and cholinergic neurodegeneration. The compound's oral activity supports its utility for in vivo studies. Detailed in vivo efficacy data, including specific model results and dosing regimens, are available in the primary literature. Alicapistat is a valuable tool for validating calpain inhibition as a therapeutic strategy for neurodegenerative diseases. |
| Enzyme Assay |
The in vitro enzyme inhibition assay for Alicapistat measures the inhibition of calpain 1 and calpain 2 enzymatic activities. Recombinant human calpain 1 or calpain 2 enzymes are incubated with varying concentrations of Alicapistat (typically ranging from nanomolar to micromolar) in the presence of a fluorescent or peptide substrate. The enzymatic reaction is monitored by measuring the cleavage of the substrate, which releases a fluorescent or chromogenic product. IC50 values are determined by fitting dose-response curves to the inhibition data (395 nM for calpain 1). The compound is dissolved in DMSO and diluted in assay buffer to achieve the desired final concentrations. Selectivity is assessed by testing the compound against other proteases. Appropriate positive controls (known calpain inhibitors) and negative controls (DMSO vehicle) are included in each assay run.
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| Cell Assay |
The in vitro cellular assay for Alicapistat is performed using neuronal cell lines or primary neurons that express calpains and are susceptible to calpain-mediated neurodegeneration. Cells are cultured in appropriate medium and treated with varying concentrations of Alicapistat or vehicle control (DMSO). Calpain activity is induced by elevating intracellular calcium levels using calcium ionophores or by glutamate exposure (excitotoxicity). Calpain activity is measured using cell-permeable fluorescent calpain substrates or by Western blotting for calpain-cleaved protein fragments (e.g., spectrin breakdown products). The inhibition of calpain activity by Alicapistat is quantified, and IC50 values are determined. Cell viability and markers of apoptosis are assessed to evaluate the neuroprotective effects of calpain inhibition.
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| Animal Protocol |
In vivo animal experiments with Alicapistat are conducted using rodent models of Alzheimer's disease or other neurodegenerative conditions. Alicapistat is administered orally at various doses due to its oral activity. Neurodegeneration is induced by appropriate means (e.g., excitotoxic lesions, amyloid-β infusion, or transgenic models of AD). Calpain activity in brain tissues is measured by Western blotting for calpain-cleaved protein fragments. Neuronal survival, synaptic integrity, and cognitive function are assessed using histology, immunohistochemistry, and behavioral tests. The compound's neuroprotective efficacy is evaluated by comparing disease severity in treated versus control groups. Detailed experimental protocols are described in the primary literature.
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| ADME/Pharmacokinetics |
Detailed pharmacokinetic (PK) parameters for Alicapistat are not extensively documented in publicly available sources. The compound is orally active. Alicapistat has a molecular weight of 433.5 and a chemical formula of C25H27N3O4. The compound is soluble in DMSO for formulation purposes. For in vivo oral administration, Alicapistat is typically formulated using appropriate vehicles to ensure adequate solubility and stability. The compound should be stored under conditions recommended by the manufacturer to maintain stability and prevent degradation. Detailed PK parameters including half-life, clearance, volume of distribution, and maximum concentration (Cmax) are available in the primary literature and should be consulted for specific experimental planning.
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| Toxicity/Toxicokinetics |
Comprehensive toxicological data for Alicapistat are not extensively documented in publicly available sources. As a research-grade compound, Alicapistat is intended for laboratory research purposes only and is not approved for human therapeutic use. Standard laboratory safety practices should be followed when handling this compound, including the use of appropriate personal protective equipment and working in a well-ventilated area. The compound should be stored according to the manufacturer's recommendations to maintain stability and prevent degradation. Comprehensive toxicological profiling (e.g., LD50, maximum tolerated dose, organ-specific toxicity) is not available from the current search results and would require consultation of the primary literature or safety data sheets.
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| References |
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| Additional Infomation |
Alicapistat is a research compound developed for studying the role of calpains in neurodegenerative diseases and for evaluating calpain inhibition as a therapeutic strategy for Alzheimer's disease. The compound is also known as ABT-957. Alicapistat is an orally active, selective inhibitor of human calpains 1 and 2, with an IC50 of 395 nM for calpain 1. Calpains 1 and 2 are believed to contribute to neuronal degeneration through excitotoxicity and cholinergic neurodegeneration. Alicapistat is not currently in clinical trials nor approved for therapeutic use; it remains an investigational tool compound for preclinical neurodegenerative disease research. Alicapistat is available from various chemical suppliers for research purposes.
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| Molecular Formula |
C25H27N3O4
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| Molecular Weight |
433.4996
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| Exact Mass |
433.2
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| CAS # |
1254698-46-8
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| Related CAS # |
(1S,2R)-Alicapistat;2221010-57-5
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| PubChem CID |
67095330
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| Appearance |
Light yellow to yellow solid powder
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| LogP |
2.4
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
9
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| Heavy Atom Count |
32
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| Complexity |
708
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| Defined Atom Stereocenter Count |
1
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| SMILES |
O=C1C([H])([H])C([H])([H])[C@]([H])(C(N([H])C([H])(C([H])([H])C2C([H])=C([H])C([H])=C([H])C=2[H])C(C(N([H])C2([H])C([H])([H])C2([H])[H])=O)=O)=O)N1C([H])([H])C1C([H])=C([H])C([H])=C([H])C=1[H]
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| InChi Key |
MMLDHJRGTZHNHV-BPGUCPLFSA-N
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| InChi Code |
InChI=1S/C25H27N3O4/c29-22-14-13-21(28(22)16-18-9-5-2-6-10-18)24(31)27-20(15-17-7-3-1-4-8-17)23(30)25(32)26-19-11-12-19/h1-10,19-21H,11-16H2,(H,26,32)(H,27,31)/t20?,21-/m1/s1
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| Chemical Name |
(2R)-1-benzyl-N-(4-(cyclopropylamino)-3,4-dioxo-1-phenylbutan-2-yl)-5-oxopyrrolidine-2-carboxamide
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| Synonyms |
ABT957; ABT 957; ABT-957
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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 : ~50 mg/mL (~115.34 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 4.17 mg/mL (9.62 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 41.7 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (5.77 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.3068 mL | 11.5340 mL | 23.0681 mL | |
| 5 mM | 0.4614 mL | 2.3068 mL | 4.6136 mL | |
| 10 mM | 0.2307 mL | 1.1534 mL | 2.3068 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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