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| 1mg |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| Targets |
(1S,2R)-Alicapistat targets human calpains 1 and 2, which are calcium-dependent cysteine proteases involved in various cellular processes. Calpain overactivation has been implicated in neurodegenerative conditions, including Alzheimer's disease. By inhibiting calpain activity, the compound may prevent the proteolysis of key proteins involved in synaptic function and neuronal survival. This mechanism supports its potential for Alzheimer's disease therapy.
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| ln Vitro |
Insufficient CNS penetration concentrations for pharmacodynamic effects are demonstrated by (1S,2R)-Alicapistat [1]. The expression of Calpain 1 (µ-calpain) and 2 (m-calpain) is dependent on calcium, requiring µ-molar or m-molar calcium concentrations for their respective activation. Compound 22 (compound 1S,2R) at 100 nM inhibits the impairments in synaptic transmission caused by Aβ oligomers in rats[2]. 22) (385 nM) exhibits effectiveness in preventing synaptic damage brought on by A and NMDA-induced neurodegeneration[2]. (1S,2R)-Alicapistat (9–21 nM) exhibits no dose-limiting toxicities (DLTs) in the large population investigations and possesses CSF concentrations without surpassing the IC50 for calpain inhibition[3].
In vitro, (1S,2R)-Alicapistat is a potent inhibitor of human calpain 1 with an IC50 of 395 nM. It selectively inhibits calpains 1 and 2. Specific cellular assay data, such as effects on neuronal cell viability or tau proteolysis, are not detailed in the available sources. |
| ln Vivo |
Compound 22 (1S,2R)-Alicapistat (iv or po; 1-3 mg/kg) has high mean plasma clearance values (1.98 L/hr.kg) in monkeys, but moderate mean plasma clearance values (CLp) in mice, rats, and dogs (0.13-1.04 L/hr.kg). Rats had greater mean steady-state volume of distribution values (Vss) (3.4 L/kg) than mice, dogs, and monkeys (0.64-1.8 L/kg). Dogs had the shortest plasma elimination half-life (t1/2) at 1.7 hours, followed by monkeys at 2.3 hours and mice and rats at roughly 6.0 hours. In mice, rats, and dogs, oral bioavailability (F) values were high (>80%), however in monkeys, they were modest (14%).
Specific in vivo activity data for (1S,2R)-Alicapistat are not provided in the available sources. As an orally active calpain inhibitor, it would be expected to have effects in animal models of Alzheimer's disease or other neurodegenerative disorders. However, no specific in vivo studies, dosing regimens, or efficacy data are described. |
| Enzyme Assay |
A cell-free assay for (1S,2R)-Alicapistat would involve measuring its inhibition of calpain enzymatic activity. In these assays, recombinant calpain 1 or 2 is incubated with a fluorogenic peptide substrate in the presence of varying concentrations of the compound. The rate of substrate cleavage is measured, and IC50 values are calculated. For (1S,2R)-Alicapistat, the IC50 for calpain 1 is 395 nM.
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| Cell Assay |
Cellular assays for (1S,2R)-Alicapistat would typically involve measuring its effects on calpain-mediated proteolysis in neuronal cells. Cells are treated with the compound, and the cleavage of calpain substrates is measured. The compound's ability to protect cells from calpain-mediated damage could also be assessed. Specific protocols are not detailed.
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| Animal Protocol |
In vivo animal experiments for (1S,2R)-Alicapistat are not described in the available sources. As a research compound with potential for Alzheimer's disease, it could be evaluated in transgenic mouse models of Alzheimer's disease. However, no specific protocols or data are provided.
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| ADME/Pharmacokinetics |
(1S,2R)-Alicapistat has a molecular formula of C25H27N3O4 and a molecular weight of 433.50. It is an orally active compound. It appears as a white to off-white solid powder. Specific pharmacokinetic parameters, such as half-life and bioavailability, are not provided in the available sources. For storage, the powder should be kept at -20°C for up to 3 years or at 4°C for up to 2 years.
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| Toxicity/Toxicokinetics |
Toxicity data for (1S,2R)-Alicapistat are not provided in the available sources. As a research compound, it is intended for research use only and not for human consumption. Standard laboratory safety precautions should be observed when handling this compound.
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| References |
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| Additional Infomation |
(1S,2R)-Alicapistat (CAS: 2221010-57-5) is an orally active, selective inhibitor of human calpains 1 and 2. It is also known as ABT-957. The compound has an IC50 of 395 nM for calpain 1 and shows promise for Alzheimer's disease therapy. Its molecular formula is C25H27N3O4 and its molecular weight is 433.50. It is not an approved drug and is strictly for research purposes.
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| Molecular Formula |
C25H27N3O4
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| Molecular Weight |
433.50
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| Exact Mass |
433.2
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| CAS # |
2221010-57-5
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| Related CAS # |
Alicapistat;1254698-46-8
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| PubChem CID |
131634149
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| Appearance |
White to off-white 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 |
2
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| SMILES |
O=C1CC[C@H](C(N[C@H](C(C(NC2CC2)=O)=O)CC2=CC=CC=C2)=O)N1CC1=CC=CC=C1
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| InChi Key |
MMLDHJRGTZHNHV-LEWJYISDSA-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+/m0/s1
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| Chemical Name |
(2R)-1-benzyl-N-[(2S)-4-(cyclopropylamino)-3,4-dioxo-1-phenylbutan-2-yl]-5-oxopyrrolidine-2-carboxamide
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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: ~25 mg/mL (~57.7 mM; with ultrasonication)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 1.25 mg/mL (2.88 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween-80 + 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 DMSO stock solution (12.5 mg/mL) to 400 μL of PEG300 and mix well; then add 50 μL of Tween-80 and mix well; finally add 450 μL of physiological saline and 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: ≥ 1.25 mg/mL (2.88 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in 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 DMSO stock solution (12.5 mg/mL) to 900 μL of 20% SBE-β-CD saline and mix well. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 3: ≥ 1.25 mg/mL (2.88 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 DMSO stock solution (12.5 mg/mL) to 900 μL of corn oil and mix well. (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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