Necrostatin-34 - ≥98% , CAS No.375835-43-1

CAS: 375835-43-1 Cat. No.: N650599 Formula: C₁₈H₁₆N₄O₂S₂ Peso molecolare: 384.5 PubChem CID: 3841655

QUALITÀ & PUREZZA ≥98%

Storage

Protected from light,Store at -80°C

Shipped In

Dry ice packs + Cold packs

Panoramica

Necrostatin-34 (Nec-34), a RIPK1 kinase inhibitor, stabilizes RIPK1 kinase in an inactive conformation by occupying a distinct binding pocket in the kinase domain.

In Vitro

Necrostatin-34 (Nec-34) exhibits IC 50 values of 667 nM and 134 nM for TNFα in FADD def-Jurkat cells and L939 cells, respectively. Necrostatin-34 (Nec-34, 10 μM) inhibits the dimerization-induced RIPK1 activation as examined by phosphorylation of Ser166 (p-S166) of RIPK1, a biomarker for RIPK1 activation. Necrostatin-34 (Nec-34) may block TNFα-induced complex II formation by inhibiting the activation of RIPK1 kinase. MCE has not independently confirmed the accuracy of these methods. They are for reference only. Western Blot AnalysisCell Line: RIPK1 knockout L929 cells transfected with an expressing vector encoding an inducible and dimerizable RIPK1 fused with FKBP at the C-terminus. Concentration: 10 μM. Incubation Time: 30 min (and then 100 ng/mL TNFα was added for indicated periods of time). Result: Downregulated p-S166 levels.

Form:Solid

Specifiche

Specifiche e purezza

≥98%

Meccanismi biochimici e fisiologici

Necrostatin-34 (Nec-34), a RIPK1 kinase inhibitor, stabilizes RIPK1 kinase in an inactive conformation by occupying a distinct binding pocket in the kinase domain.

Condizioni di conservazione di stoccaggio

Protected from light,Store at -80°C

Spedito in

Dry ice packs + Cold packs

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Tipo di azione

INHIBITOR

Purezza

≥98%

Nomi e identificatori

Sorrisi canonici

CC1=CC=C(C=C1)C2CC(=O)NC(=C2C#N)SCC(=O)NC3=NC=CS3

IUPAC Name

2-[[5-cyano-4-(4-methylphenyl)-2-oxo-3,4-dihydro-1H-pyridin-6-yl]sulfanyl]-N-(1,3-thiazol-2-yl)acetamide

InChIKey

LOQIRQHGJVGIEL-UHFFFAOYSA-N

INCHI

1S/C18H16N4O2S2/c1-11-2-4-12(5-3-11)13-8-15(23)21-17(14(13)9-19)26-10-16(24)22-18-20-6-7-25-18/h2-7,13H,8,10H2,1H3,(H,21,23)(H,20,22,24)

Isomeri SMILES

CC1=CC=C(C=C1)C2CC(=O)NC(=C2C#N)SCC(=O)NC3=NC=CS3

PubChem CID

3841655

Peso molecolare

384.5

Taxonomic Classification

Taxonomy Tree

• Kingdom Organic compounds
  • Superclass Organic nitrogen compounds
    • Classe Organonitrogen compounds
      • Subclass N-arylamides

• Kingdom: Organic compounds
• Superclass: Organic nitrogen compounds
• Classe: Organonitrogen compounds
• Subclass: N-arylamides
• Intermediate Tree Nodes: Not available
• Direct Parent: N-arylamides
• Alternative Parents: Toluenes Tetrahydropyridines Thiazoles Heteroaromatic compounds Secondary carboxylic acid amides Lactams Ketene acetals Sulfenyl compounds Nitriles Azacyclic compounds Organic oxides Hydrocarbon derivatives Carbonyl compounds
• Molecular Framework: Aromatic heteromonocyclic compounds
• Substituents: N-arylamide - Tetrahydropyridine - Toluene - Monocyclic benzene moiety - Hydropyridine - Benzenoid - Heteroaromatic compound - Azole - Thiazole - Carboxamide group - Ketene acetal or derivatives - Lactam - Secondary carboxylic acid amide - Organoheterocyclic compound - Azacycle - Carboxylic acid derivative - Sulfenyl compound - Carbonitrile - Nitrile - Carbonyl group - Organic oxide - Cyanide - Hydrocarbon derivative - Organooxygen compound - Organosulfur compound - Organic oxygen compound - Aromatic heteromonocyclic compound
• Descrizione: This compound belongs to the class of organic compounds known as n-arylamides. These are organic compounds that contain a carboxamide group that is N-linked to a aryl group. They have the generic structure RC(=O)N(R')H, R = organyl group and R'= aryl group.
• External Descriptors: Not available

Data sources

1. Djoumbou Feunang Y, Eisner R, Knox C, Chepelev L, Hastings J, Owen G, Fahy E, Steinbeck C, Subramanian S, Bolton E, Greiner R, and Wishart DS. ClassyFire: Automated Chemical Classification With A Comprehensive, Computable Taxonomy. Journal of Cheminformatics, 2016, 8:61.

DOI: 10.1186/s13321-016-0174-y

Obiettivi associati (umani)

GLP1R Tclin Glucagon-like peptide 1 receptor (111429 Activities)

Discover Target: GLP1R

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

SMN1 Tchem Survival motor neuron protein (34246 Activities)

Discover Target: SMN1

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

Obiettivi associati (non umani)

fadD28 Acyl-CoA synthase (418 Activities)

Discover Target: fadD28

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

Mapt Microtubule-associated protein tau (6 Activities)

Discover Target: Mapt

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

Meccanismi d'azione

Proprietà chimiche e fisiche

• Solubilità: DMSO : 125 mg/mL (325.11 mM; Need ultrasonic)
• Peso molecolare: 384.500 g/mol
• XLogP3: 2.200
• Hydrogen Bond Donor Count: 2
• Hydrogen Bond Acceptor Count: 6
• Rotatable Bond Count: 5
• Exact Mass: 384.071 Da
• Monoisotopic Mass: 384.071 Da
• Topological Polar Surface Area: 148.000 Ų
• Heavy Atom Count: 26
• Formal Charge: 0
• Complexity: 634.000
• Isotope Atom Count: 0
• Defined Atom Stereocenter Count: 0
• Undefined Atom Stereocenter Count: 1
• Defined Bond Stereocenter Count: 0
• Undefined Bond Stereocenter Count: 0
• The total count of all stereochemical bonds: 0
• Covalently-Bonded Unit Count: 1

Application Protocols

Item-specific, validated application protocols and recommended dilutions are not provided for this product.

General guidance for small-molecule use in cell-based and biochemical assays (NOT item-specific specifications):

• Stock preparation: Dissolve in anhydrous DMSO to 10–50 mM. Vortex and, if needed, gently warm to 25–37 °C and sonicate briefly. Filter sterilize (0.22 µm PTFE) if sterility is required.
• Aliquoting: Dispense single-use aliquots to avoid freeze–thaw cycles. Store at −80 °C protected from light.
• Dosing: Prepare serial dilutions in assay buffer/media, keeping final DMSO ≤0.1–0.5% v/v. Include vehicle-only controls and, where appropriate, orthogonal tool compounds.
• Readouts: Combine viability assays (e.g., ATP-based, membrane integrity) with pathway biomarkers to confirm mechanism in your model. Define exposure time and concentration through preliminary titrations and time-course studies.
• Data quality: Use biological replicates (≥3), randomization, and blinding where feasible. Confirm compound integrity by LC–MS/HPLC if experiments span multiple weeks.

For protocol development tailored to your system, consult primary literature on necrostatin analogs and adapt to your cell type, assay platform, and detection method.

Biological Roles

• Context (literature/general for necrostatin chemotypes; NOT an item-specific claim):

  • Necrostatins are widely used as chemical biology probes in the study of regulated necrosis (necroptosis), a programmed cell death pathway that is mechanistically distinct from apoptosis. Many necrostatins have been reported to inhibit RIPK1 kinase activity, a key initiator of necroptotic signaling, though selectivity and potency vary across analogs and assay formats.

• Experimental applications (general):

  • Dissection of TNF-family signaling outcomes (survival vs apoptosis vs necroptosis) by pharmacological modulation combined with caspase inhibition and/or genetic perturbations.
  • Assessment of necroptosis biomarkers (e.g., phosphorylation/oligomerization events within the necrosome) and downstream consequences such as membrane integrity loss and DAMP release in cell models.
  • Use in temporal studies (pre-, co-, post-treatment) to map pathway kinetics and checkpoint dependencies.

• Best practices (general):

  • Validate pathway engagement with orthogonal readouts (e.g., RIPK1 phosphorylation state, MLKL activation) and counter-screen against unrelated kinases or stress pathways to assess specificity.
  • Include cytotoxicity controls and vehicle-only controls; maintain DMSO at minimal levels.

• Important note:

  • The precise target profile, potency, and selectivity for Necrostatin-34 specifically are not provided here and should be confirmed from the CoA/Spec Sheet and peer-reviewed primary literature before drawing mechanistic conclusions in your system.

Buffer Applications

This item is a small-molecule research tool, not a buffering agent. It does not serve as a pH buffer component.

Practical guidance (general for bioactive small molecules in buffers):

• Prepare concentrated DMSO stocks and dilute into pre-warmed assay buffer or culture medium immediately before use, targeting a final DMSO content ≤0.1–0.5% v/v.
• If aqueous solubility is limited, include a small amount of co-solvent (DMSO) and consider nonionic surfactants at very low levels, consistent with your assay’s tolerance. Filter sterilize working solutions (0.22 µm) when sterility is required.
• Avoid strong alkaline buffers unless confirmed stable. Protect from light as specified.

All item-specific buffer compatibility parameters are not specified for this item; refer to CoA/Spec Sheet and verify empirically in your assay system.

Green Alternatives

As a bioactive tool compound, this product is not a general-purpose solvent or reagent where greener drop-in replacements are typically considered. However, greener practices can be applied to its handling and use:

• Solvent considerations (general):

  • Prefer aqueous buffers with minimal DMSO (≤0.1–0.5% v/v) for biological assays. Where organic solvents are required for analytical sample prep, consider ethanol or isopropanol in place of chlorinated solvents when compatible.
  • For chromatographic purification/analysis (if applicable), explore ethanol/heptane or water/acetonitrile systems rather than DCM/hexanes. Validate solubility and selectivity.

• Process minimization:

  • Prepare concentrated stocks to reduce solvent volumes. Use microplate formats and miniaturized assays to minimize waste.

• Energy and storage:

  • The specified −80 °C storage is necessary for stability; mitigate energy impact by aliquoting to reduce door-open time and by consolidating ultra-low-temperature storage where institutional policies allow.

• Waste and safety:

  • Segregate halogenated from non-halogenated waste. Use closed, low-dead-volume systems for dosing to reduce volatilization and operator exposure.

Because this is a specialized screening compound rather than a commodity solvent, there are no recognized “green alternative compounds” that substitute for its biological activity; instead, focus on greener solvents and right-sizing experimental design.

Pharmaceutical Uses

This product is supplied strictly for research use only and is not intended for human or veterinary use, diagnostic procedures, or as an excipient in marketed formulations.

General, non-clinical R&D context (not item-specific claims):

• Small-molecule tool compounds like necrostatin analogs are used in early discovery to probe target/pathway relevance, inform medicinal chemistry campaigns, and serve as positive controls in phenotypic or target-based assays.
• Formulation screening in preclinical research may explore solubilization strategies (e.g., DMSO-based vehicles, cyclodextrin inclusion, micellar systems) for in vitro or ex vivo studies; any such use requires comprehensive safety and stability evaluation.

Regulatory status:

• No pharmacopeial monograph or GMP status is provided. Any application outside basic research would require new safety, quality, and regulatory assessments.

Item-specific details such as excipient roles, compendial status, or clinical formulation guidance are not specified for this item; consult the CoA/Spec Sheet if additional information becomes available.

Physical Properties

• Item-specific physical data:

  • Appearance: Not specified for this item; refer to CoA/Spec Sheet.
  • Grade/Purity: Not specified for this item; refer to CoA/Spec Sheet.
  • Molecular Weight: Not specified for this item; refer to CoA/Spec Sheet.
  • Molecular Formula: Not specified for this item; refer to CoA/Spec Sheet.

• Basic thermophysical properties (literature/general for necrostatin-like small molecules; NOT item-specific):

  • Many necrostatin analogs are crystalline solids at ambient conditions and exhibit low aqueous solubility, with high solubility in polar aprotic organics (e.g., DMSO, DMF) (literature).
  • Boiling point, melting point, density, logP/logD, pKa, and refractive index for Necrostatin-34 are not available in the provided data; consult the CoA/Spec Sheet or primary literature.

• Solubility guidance (general, not item-specific):

  • Typical stock preparation for similar screening compounds is 10–50 mM in anhydrous DMSO due to hydrophobic character and assay convenience (literature). Aqueous working solutions are commonly prepared by diluting the DMSO stock into buffered media while maintaining DMSO ≤0.1–0.5% v/v to minimize vehicle effects.

• Note: For any exact value needed in method validation or regulatory documentation, use the CoA/Spec Sheet or independently measure under your laboratory conditions.

Quality and Grades

• Item-specific quality information:

  • Grade/Purity: Not specified for this item; refer to CoA/Spec Sheet.
  • Stabilizers/Additives: Not specified for this item; refer to CoA/Spec Sheet.

• How to interpret grades for small-molecule tool compounds (general guidance):

  • Screening/biological grade typically emphasizes high chemical purity (often ≥95% by HPLC/UPLC) and low residual solvents/metals to reduce assay artifacts. However, exact thresholds are specification-dependent; rely on the CoA for this SKU.
  • Chromatographic purity does not guarantee biological specificity. Verify target engagement with orthogonal assays and, when possible, use inactive analogs or counter-screens to control for off-target effects.

• Documentation and traceability:

  • For publication-quality work, record the batch/lot number and attach the CoA, chromatograms, water content, and any NMR/HRMS data supplied. If UV cutoff or residual peroxide/metal limits are critical to your workflow, confirm via CoA or request additional documentation.

• Practical notes:

  • Bioactive heteroaromatics can be light- and air-sensitive; the specified −80 °C, light-protected storage supports shelf life. If long-term studies are planned, consider performing incoming QC (HPLC purity, identity by MS/NMR) upon receipt and again after prolonged storage.

Reaction and Applications

This product is supplied as a small-molecule research tool compound. It is not primarily used as a reagent or building block for synthetic transformations; therefore, classic reaction families (e.g., cross-coupling, Grignard, reductions) are not typically applicable to this SKU.

Relevant applications (general/literature for necrostatin-class compounds; NOT item-specific claims):

• Chemical biology tool for interrogating pathways of regulated necrosis (necroptosis) in cell and biochemical systems.
• Use in time-of-addition experiments to delineate upstream vs downstream events in cell death signaling.
• Employed in target validation workflows with orthogonal inhibitors and genetic perturbations to assess pathway dependence.
• Utilized in phenotypic screening cascades as a positive control for necroptosis pathway modulation, with follow-up assays (e.g., kinase activity, substrate phosphorylation, cell viability).

Practical tips (general):

• Include appropriate vehicle controls and, where feasible, inactive or chemotype-distinct control compounds to discriminate on-target from off-target effects.
• Verify compound integrity by analytical HPLC and MS if stored for extended periods or subjected to freeze–thaw.
• If mechanism-of-action studies are intended, complement small-molecule data with genetic knockdown/knockout to strengthen causal inference.

Note: For any use beyond pathway interrogation (e.g., as a synthetic intermediate), consult primary literature procedures; no such applications are specified for this item.

Reaction Conditions

Classic chemical reaction conditions are not applicable because this product is not supplied as a reagent for carrying out chemical transformations.

Assay-use conditions (general guidance for bioactive small molecules; NOT item-specific):

• Stock solutions: 10–50 mM in anhydrous DMSO; store aliquots at −80 °C protected from light.
• Working concentrations: Typically in the nM–µM range depending on assay sensitivity and compound potency; determine empirically with dose–response curves and appropriate vehicle controls.
• Incubation: Pre-incubation with cells or enzymes for 15–60 min is common in mechanism studies; optimize contact time and temperature (often 25–37 °C) for your model.
• Compatibility: Avoid high serum protein when nonspecific binding is suspected; consider using BSA-free buffers for in vitro biochemistry unless stabilization is needed.

Important: None of the above constitutes item-specific specifications. For any exact operating conditions or stability data of Necrostatin-34, consult CoA/Spec Sheet and validate under your laboratory conditions.

Safety and Handling

• GHS and hazard data (item-specific):

  • Signal Word: Not specified for this item; refer to SDS.
  • H-Statements: Not specified for this item; refer to SDS.
  • GHS Classification: Not specified for this item; refer to SDS.
  • Pictograms: Not specified for this item; refer to SDS.

• Storage and shipping (item-specific from Product Data):

  • Storage: Protect from light; store at −80 °C.
  • Shipping: Dry ice packs + cold packs.

• General handling guidance for bioactive research small molecules (literature/best practice):

  • Use in a chemical fume hood; avoid inhalation, ingestion, and skin contact. Wear appropriate PPE: lab coat, safety glasses, and nitrile gloves. Minimize exposure to ambient moisture and heat; many screening compounds can degrade by hydrolysis/oxidation.
  • Prepare aliquots to avoid repeated freeze–thaw cycles. Allow vials to equilibrate to room temperature in a desiccator before opening to prevent condensation ingress.
  • Incompatibilities: Avoid strong oxidizers and strong acids/bases unless compatibility is known. Keep away from light to mitigate photodegradation as directed.

• First-aid overview (general):

  • Skin/eye contact: Rinse with water for ≥15 min; remove contaminated clothing. Inhalation: move to fresh air. Ingestion: do not induce vomiting; seek medical attention. Always consult the product SDS for authoritative, item-specific instructions.

• Waste: Collect organic solvent solutions and contaminated disposables as hazardous chemical waste according to institutional and local regulations.

Solvent Selection

• Polarity and miscibility profile (general for necrostatin-like small molecules; NOT item-specific):

  • Preferred stock solvent: DMSO, owing to strong solvating power for aromatic/heteroaromatic scaffolds and excellent compatibility with biochemical and cell-based assays.
  • Alternative solvents for preparative work: DMF, DMAc, NMP (high solvency; less favored for biological assays), and chlorinated solvents (e.g., DCM, CHCl3) for synthetic/analytical steps. Ethanol or methanol may dissolve some analogs at modest concentrations; aqueous solubility is typically low without co-solvent or surfactant.

• Practical recommendations (general):

  • Prepare concentrated anhydrous DMSO stocks (e.g., 10–50 mM), then dilute into the assay buffer/media immediately before use. Maintain final DMSO ≤0.1–0.5% v/v to limit cytotoxic or assay-interference effects.
  • For kinetic/biophysical assays, pre-screen vehicle effects and, if needed, include matched vehicle controls across titrations.
  • For poorly soluble cases, consider gentle warming (≤37 °C) and brief sonication. Avoid alkaline aqueous solutions unless stability is documented.

• Comparison notes (general):

  • DMSO vs DMF in biology: DMSO is generally preferred due to lower intrinsic bioactivity and better cell compatibility; DMF is more cytotoxic and is typically avoided in live-cell work.
  • Aqueous vehicles with solubilizers (e.g., 0.5–1% v/v DMSO + 0.01–0.05% nonionic surfactant) can improve delivery while preserving assay integrity. Validate experimentally.

Storage and Reconstitution

• Storage conditions (item-specific from Product Data):

  • Store at −80 °C, protected from light.
  • Shipped on dry ice packs + cold packs.

• Stability considerations (general guidance, not item-specific):

  • Avoid repeated freeze–thaw. Open vials only after equilibrating to room temperature in a desiccated environment to prevent condensation. Protect from ambient light during handling and storage.

• Reconstitution (general guidance for necrostatin-like small molecules):

  • Solvent: Anhydrous DMSO is commonly used for initial stock solutions (e.g., 10–50 mM). Mix thoroughly; if needed, apply brief sonication and gentle warming (≤37 °C).
  • Filtration: For sterile applications, pass through a 0.22 µm PTFE syringe filter into sterile vials.
  • Aliquoting: Dispense into single-use portions, flush headspace with inert gas if feasible, and store at −80 °C protected from light.
  • Working solutions: Prepare immediately before use by diluting the DMSO stock into buffer/media. Keep final DMSO content minimal (typically ≤0.1–0.5% v/v) and verify compatibility with your assay.

• Expiry and QC:

  • No item-specific shelf-life is provided; refer to CoA/Spec Sheet. For long-term studies, periodically confirm identity/purity by LC–MS or HPLC to ensure consistent performance.

Structure and Identity

• Item-specific identifiers (from Product Data):

  • SKU: N650599
  • Product Name: Necrostatin-34
  • CAS: 375835-43-1
  • PubChem CID: 3841655
  • InChIKey (as provided): 205137
  • SMILES: Not specified for this item; refer to CoA/Spec Sheet.
  • Molecular Formula: Not specified for this item; refer to CoA/Spec Sheet.
  • Molecular Weight: Not specified for this item; refer to CoA/Spec Sheet.

• Structural features (general/literature context, not item-specific):

  • “Necrostatins” are a family of small molecules developed as tool compounds for studying regulated necrosis (necroptosis). Many members of this series are heteroaromatic scaffolds bearing amide/urea and/or indole-like motifs (literature), though exact functionalities vary by analog number.
  • Without a provided structure for Necrostatin-34, detailed functional groups, ring systems, and stereochemistry cannot be confirmed for this specific item; consult the CoA/Spec Sheet and primary literature for definitive structure.

• 2D structure description (general guidance):

  • In the necrostatin series, planar heteroaromatic cores with substituents capable of hydrogen bonding and hydrophobic interactions are common (literature). Exact atomic connectivity for Necrostatin-34 is not specified here and should be verified from the certificate of analysis or peer-reviewed sources.

Synthetic Utility

This SKU is offered as a finished small-molecule research tool and is not positioned as a synthetic building block. Consequently, synthetic applications such as protection strategies, cross-couplings, or functional group interconversions are not typically relevant to its intended use.

General notes (if considering derivatization for SAR studies; literature-level, not item-specific):

• Necrostatin chemotypes often tolerate substitutions around their heteroaromatic core to modulate potency, solubility, and selectivity. Common medicinal chemistry moves include heteroatom substitution, amide/urea modifications, and lipophilicity tuning.
• When derivatization is attempted, maintain analytical control (HPLC, HRMS, 1H/13C NMR) to ensure purity and structural assignment; small impurities can confound biological readouts.

Because no functional group profile is provided for Necrostatin-34 in the current data set, specific synthetic transformations, protecting-group strategies, or named-reaction routes cannot be recommended. Refer to primary literature and the CoA/Spec Sheet for structural details before planning any synthesis or modification.

Target Specificity

Item-specific target, selectivity, and potency data are not provided for this product. No antigen/epitope/clone information applies because this is a small-molecule compound rather than an antibody or protein reagent.

General note (not item-specific): Members of the necrostatin series are widely used as pathway probes in necroptosis research; specific molecular targets and selectivity profiles vary and should be verified from primary literature for the exact analog and lot in use.

Please refer to the CoA/Spec Sheet or contact technical support for any available target engagement data specific to SKU N650599.

Domande frequenti

What is the purity of this product?

This product is supplied at ≥98% purity (chemical assay). Lot-specific values are stated on the Certificate of Analysis.

How should this product be stored?

Store at ?80 °C, protected from light. The material is light-sensitive — keep it in its original opaque or amber container.

How is this product shipped?

This product ships frozen with dry ice and cold packs. Unpack on arrival and transfer it to the storage condition stated above; handle dry ice with insulated gloves in a ventilated area.

What are the CAS number, molecular formula and molecular weight?

The CAS Number is 375835-43-1, the molecular formula is C18H16N4O2S2, and the molecular weight is 384.5 g/mol. InChIKey LOQIRQHGJVGIEL-UHFFFAOYSA-N.

What documentation is provided?

Available product documentation, including Certificates of Analysis (COA), Safety Data Sheets (SDS), and specification sheets, is shown in the product document area. Document availability and access follow the current site policy.