| Size | Price | |
|---|---|---|
| 50mg | ||
| 100mg | ||
| Other Sizes |
Purity: ≥98%
Alicapistat (also known as ABT957; ABT-957) is a novel, potent, selective and orally bioactive inhibitor of human calpains 1 and 2 whose overactivation has been linked to Alzheimer disease (AD). It has the potential usefulness in the treatment of Alzheimer's disease (AD). In clinical trials, Alicapistat at 400- or 800-mg twice-daily doses had no effect on REM sleep parameters, whereas the active control, donepezil at 10 mg twice daily, affected sleep parameters. Across all trials, the incidence of treatment-emergent adverse events was similar in the placebo and alicapistat groups. There were no clinically significant changes in vital signs and laboratory measurements. The lack of an effect of alicapistat on sleep suggests that concentrations in the CNS were inadequate or that preclinical studies do not predict alicapistat effects in humans.
| 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].
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| 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].
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| References |
[1]. Lon HK, et al. Pharmacokinetics, Safety, Tolerability, and Pharmacodynamics of Alicapistat, a Selective Inhibitor of Human Calpains 1 and 2 for the Treatment of Alzheimer Disease: An Overview of Phase 1 Studies. Clin Pharmacol Drug Dev. 2018 Jul 27.
[2]. Jantos K, et al. Discovery of ABT-957: 1-Benzyl-5-oxopyrrolidine-2-carboxamides as selective calpain inhibitors with enhanced metabolic stability. Bioorg Med Chem Lett. 2019 Aug 1. 29(15):1968-1973. [3]. Jastaniah A, Gaisina IN, Knopp RC, Thatcher GRJ. Synthesis of α-Ketoamide-Based Stereoselective Calpain-1 Inhibitors as Neuroprotective Agents. ChemMedChem. 2020 Dec 3. 15(23):2280-2285. |
| Molecular Formula |
C25H27N3O4
|
|---|---|
| Molecular Weight |
433.4996
|
| CAS # |
1254698-46-8
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| Related CAS # |
(1S,2R)-Alicapistat;2221010-57-5
|
| SMILES |
O=C([C@@H](CC1)N(CC2=CC=CC=C2)C1=O)NC(C(C(NC3CC3)=O)=O)CC4=CC=CC=C4
|
| InChi Key |
MMLDHJRGTZHNHV-BPGUCPLFSA-N
|
| 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
|
| Chemical Name |
(2R)-1-benzyl-N-(4-(cyclopropylamino)-3,4-dioxo-1-phenylbutan-2-yl)-5-oxopyrrolidine-2-carboxamide
|
| Synonyms |
ABT957; ABT 957; ABT-957
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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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