| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| 10mg |
|
||
| 25mg |
|
||
| 50mg |
|
||
| 100mg | |||
| Other Sizes |
| 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.
|
|---|---|
| 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.
|
| 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.
|
| 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.
|
| 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.
|
| 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.
|
| References |
|
| 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.
|
| Molecular Formula |
C25H27N3O4
|
|---|---|
| Molecular Weight |
433.50
|
| Exact Mass |
433.2
|
| CAS # |
2221010-57-5
|
| Related CAS # |
Alicapistat;1254698-46-8
|
| PubChem CID |
131634149
|
| Appearance |
White to off-white solid powder
|
| LogP |
2.4
|
| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
4
|
| Rotatable Bond Count |
9
|
| Heavy Atom Count |
32
|
| Complexity |
708
|
| Defined Atom Stereocenter Count |
2
|
| SMILES |
O=C1CC[C@H](C(N[C@H](C(C(NC2CC2)=O)=O)CC2=CC=CC=C2)=O)N1CC1=CC=CC=C1
|
| InChi Key |
MMLDHJRGTZHNHV-LEWJYISDSA-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+/m0/s1
|
| Chemical Name |
(2R)-1-benzyl-N-[(2S)-4-(cyclopropylamino)-3,4-dioxo-1-phenylbutan-2-yl]-5-oxopyrrolidine-2-carboxamide
|
| HS Tariff Code |
2934.99.9001
|
| 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)
|
| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
|
|---|---|
| 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 | 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
