Necrostatin 2 R-isomer

Alias: Necrostatin-2 R-isomer; Necrostatin 2; (±)-Necrostatin-2; Necrostatin-2 racemate; 7-Cl-O-Nec-1; Nec-1S
Cat No.:V3292 Purity: ≥98%
Necrostatin 2 R-isomer is the R-enantiomer of Necrostatin 2 (also known asNecrostatin-2, Necrostatin-2 racemate, (±)-Necrostatin-2, 7-Cl-O-Nec-1 and Nec-1s) which is a potent necroptosis inhibitor with EC50 of 50 nM.
Necrostatin 2 R-isomer Chemical Structure CAS No.: 852391-19-6
Product category: RIP kinase
This product is for research use only, not for human use. We do not sell to patients.
Size Price Stock Qty
10mg
25mg
50mg
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Other Sizes

Other Forms of Necrostatin 2 R-isomer:

  • Necrostatin-2 racemate
  • Necrostatin 2 S enantiomer
Official Supplier of:
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Purity & Quality Control Documentation

Purity: ≥98%

Product Description

Necrostatin 2 (also known as Necrostatin-2, Necrostatin-2 racemate, (±)-Necrostatin-2, 7-Cl-O-Nec-1 and Nec-1s) is a powerful necroptosis inhibitor with an EC50 of 50 nM. It is a racemic mixture that prevents the autophosphorylation of the receptor-interacting protein kinase 1 (RIPK1). A controlled caspase-independent cell death mechanism called necroptosis produces morphological characteristics that resemble necrosis. It can be brought on by TNF-alpha-treated human Jurkat T cells with a FADD-deficient variant. Additionally effective in an animal model of ischemic stroke, necrostatin 2 was. After being administered intravenously, necrostatin 2 showed moderate pharmacokinetic properties and quickly entered the central nervous system.

Biological Activity I Assay Protocols (From Reference)
Targets
Necroptosis; RIPK1
ln Vitro
Nec-1s is a potent inhibitor of RIPK1 and cellular necroptosis while lacking IDO inhibitory activity[1].
ln Vivo
Necrostatin 2 R-isomer(Nec-1s) is effective at minimizing brain injuries. It is a superior inhibitor that can be used in vivo and does not have a paradoxical sensitizing effect in TNF-induced lethality[1].
Necrostatin 2 R-isomer(Nec-1s) differs from Nec-1 in that it has a number of favorable pharmacokinetic and pharmacodynamic properties. Because of their lower in vivo and in vitro toxicity, Nec-1s have a safer safety profile than Nec-1[2].
Enzyme Assay
Necrostatin 2 (also known as Necrostatin-2, Necrostatin-2 racemate, (±)-Necrostatin-2, 7-Cl-O-Nec-1 and Nec-1s, is a potent necroptosis inhibitor with EC50 of 50 nM.
Cell Assay
Cells were treated with indicated concentrations of drug.
Animal Protocol


References

[1]. Cell Death Dis . 2012 Nov 29;3(11):e437.

[2]. Molecules . 2018 Aug 3;23(8):1946.

[3]. Cell Rep . 2022 Oct 4;41(1):111434.

These protocols are for reference only. InvivoChem does not independently validate these methods.
Physicochemical Properties
Molecular Formula
C13H12CLN3O2
Molecular Weight
277.71
Exact Mass
277.0618
Elemental Analysis
C, 56.23; H, 4.36; Cl, 12.77; N, 15.13; O, 11.52
CAS #
852391-19-6
Related CAS #
Necrostatin 2 racemate;852391-15-2;Necrostatin 2 S enantiomer;852391-20-9
Appearance
Solid powder
SMILES
CN1C(=O)[C@H](NC1=O)CC2=CNC3=C2C=CC=C3Cl
InChi Key
WIKGAEMMNQTUGL-SNVBAGLBSA-N
InChi Code
InChI=1S/C13H12ClN3O2/c1-17-12(18)10(16-13(17)19)5-7-6-15-11-8(7)3-2-4-9(11)14/h2-4,6,10,15H,5H2,1H3,(H,16,19)/t10-/m1/s1
Chemical Name
(5R)-5-[(7-chloro-1H-indol-3-yl)methyl]-3-methylimidazolidine-2,4-dione
Synonyms
Necrostatin-2 R-isomer; Necrostatin 2; (±)-Necrostatin-2; Necrostatin-2 racemate; 7-Cl-O-Nec-1; Nec-1S
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 Data
Solubility (In Vitro)
DMSO: ~10 mM
Water: N/A
Ethanol: N/A
Solubility (In Vivo)
Solubility in Formulation 1: ≥ 2.5 mg/mL (9.00 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 25.0 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 (9.00 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 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
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.

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Solubility in Formulation 3: ≥ 2.5 mg/mL (9.00 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 3.6009 mL 18.0044 mL 36.0088 mL
5 mM 0.7202 mL 3.6009 mL 7.2018 mL
10 mM 0.3601 mL 1.8004 mL 3.6009 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.

Calculator

Molarity Calculator allows you to calculate the mass, volume, and/or concentration required for a solution, as detailed below:

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An example of molarity calculation using the molarity calculator is shown below:
What is the mass of compound required to make a 10 mM stock solution in 5 ml of DMSO given that the molecular weight of the compound is 350.26 g/mol?
  • Enter 350.26 in the Molecular Weight (MW) box
  • Enter 10 in the Concentration box and choose the correct unit (mM)
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  • The answer of 17.513 mg appears in the Mass box. In a similar way, you may calculate the volume and concentration.

Dilution Calculator allows you to calculate how to dilute a stock solution of known concentrations. For example, you may Enter C1, C2 & V2 to calculate V1, as detailed below:

What volume of a given 10 mM stock solution is required to make 25 ml of a 25 μM solution?
Using the equation C1V1 = C2V2, where C1=10 mM, C2=25 μM, V2=25 ml and V1 is the unknown:
  • Enter 10 into the Concentration (Start) box and choose the correct unit (mM)
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  • The answer of 62.5 μL (0.1 ml) appears in the Volume (Start) box
g/mol

Molecular Weight Calculator allows you to calculate the molar mass and elemental composition of a compound, as detailed below:

Note: Chemical formula is case sensitive: C12H18N3O4  c12h18n3o4
Instructions to calculate molar mass (molecular weight) of a chemical compound:
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Definitions of molecular mass, molecular weight, molar mass and molar weight:
  • Molecular mass (or molecular weight) is the mass of one molecule of a substance and is expressed in the unified atomic mass units (u). (1 u is equal to 1/12 the mass of one atom of carbon-12)
  • Molar mass (molar weight) is the mass of one mole of a substance and is expressed in g/mol.
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In vivo Formulation Calculator (Clear solution)
Step 1: Enter information below (Recommended: An additional animal to make allowance for loss during the experiment)
Step 2: Enter in vivo formulation (This is only a calculator, not the exact formulation for a specific product. Please contact us first if there is no in vivo formulation in the solubility section.)
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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.

Biological Data
  • Activity of Nec-1, Nec-1i and Nec-1s in an in vitro RIPK kinase assay and a cellular assay for necroptosis. Cell Death Dis . 2012 Nov 29;3(11):e437.
  • Molecular docking of substrates, inhibitors and Nec-1 variants on human IDO. Cell Death Dis . 2012 Nov 29;3(11):e437.
  • Molecular docking of substrates, inhibitors and Nec-1 variants on human IDO representing a similar docking pose for all ligands. Cell Death Dis . 2012 Nov 29;3(11):e437.
  • Nec-1/1-M-Trp and Nec-1i, but not Nec-1s, inhibit IDO activity. Cell Death Dis . 2012 Nov 29;3(11):e437.
  • Nec-1 and Nec-1i show a paradoxical dose response in TNF-induced SIRS. Cell Death Dis . 2012 Nov 29;3(11):e437.
  • Nec-1s does not show a paradoxical dose response in TNF-induced SIRS. Cell Death Dis . 2012 Nov 29;3(11):e437.
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