VE-821 - Moligand™, 10mM in DMSO , Inhibitor of ATR serine/threonine kinase, CAS No.1232410-49-9, Inhibitor of ATR serine/threonine kinase

CAS: 1232410-49-9 Cat. No.: V408304 Fórmula: C₁₈H₁₆N₄O₃S Peso molecular: 368.41 PubChem CID: 51000408

GRADE & PURITY Moligand™, 10mM in DMSO

Synonyms

2-Pyrazinecarboxamide, 3-amino-6-[4-(methylsulfonyl)phenyl]-N-phenyl-

Storage

Store at -80°C

Shipped In

Dry ice packs + Cold packs

Descripción general

Information

VE-821 is a potent and selective ATP competitive inhibitor ofATRwithKi/IC50of 13 nM/26 nM in cell-free assays, shows inhibition of H2AX phosphorylation, minimal activity against PIKKs ATM, DNA-PK, mTOR and PI3Kγ.
In vitro

VE-821 shows excellent selectivity for ATR with minimal cross-reactivity against the related PIKKs ATM, DNA-PK, mTOR and PI3K (K_is of 16 μM, 2.2 μM, >1 μM and 3.9 μM, respectively. VE-821 alone commits a large fraction of cancer cell populations to death, but it only reversibly limits cell cycle progression in normal cells, with minimal death or long-term detrimental effects. VE-821 along with cisplatin treatment shows the most marked synergy. VE-821 inhibits H2AX cell growth with IC50 of 800 nM.

In vivo

Cell Data

cell lines：

Concentrations：--

Incubation Time：96 hours

Powder Purity:≥99%

Specifications

Sinónimos

2-Pyrazinecarboxamide, 3-amino-6-[4-(methylsulfonyl)phenyl]-N-phenyl-

Especificaciones y pureza

Moligand™, 10mM in DMSO

Mecanismos bioquímicos y fisiológicos

VE-821 is a potent and selective ATP competitive inhibitor of ATR with K_i/IC50 of 13 nM/26 nM in cell-free assays, shows inhibition of H2AX phosphorylation, minimal activity against PIKKs ATM, DNA-PK, mTOR and PI3Kγ.

Condiciones de almacenamiento de almacenamiento

Store at -80°C

Enviado en

Dry ice packs + Cold packs

Este producto requiere envío en cadena de frío. Los servicios terrestres y otros servicios económicos no están disponibles.

Grado

Moligand™

Tipo de acción

INHIBITOR

Mecanismo de acción

Inhibitor of ATR serine/threonine kinase

Nombres e identificadores

Isómeros SMILES

CS(=O)(=O)C1=CC=C(C=C1)C2=CN=C(C(=N2)C(=O)NC3=CC=CC=C3)N

PubChem CID

51000408

Peso molecular

368.41

Objetivos asociados (humanos)

PRKDC Tchem DNA-dependent protein kinase catalytic subunit (1 Activities)

Discover Target: PRKDC

Activity Type	Activity Value -log(M)	Mechanism of Action	Activity Reference	Publications (PubMed IDs)

ATR Tchem Serine/threonine-protein kinase ATR (2 Activities)

Discover Target: ATR

Activity Type	Activity Value -log(M)	Mechanism of Action	Activity Reference	Publications (PubMed IDs)

Propiedades químicas y físicas

• Solubilidad: Solubility (25°C) In vitro DMSO: 56 mg/mL (201.62 mM); Ethanol: 8 mg/mL (28.8 mM); Water: Insoluble

Application Protocols

Item-specific validated applications and conditions are not provided for this product entry.

What this means:

• No vendor-tested protocols, dilutions, or positive controls are specified for this item; refer to CoA/Spec Sheet.

General planning notes (not protocols and not item-specific):

• Design experiments with appropriate solvent controls, dose–response curves, and time-course evaluations.
• Confirm compound identity and working concentration before critical studies.

For detailed, validated procedures, consult peer-reviewed literature on small-molecule tool compounds in the relevant pathway and adapt to your system with appropriate controls.

Biological Roles

Item-specific target details are not provided in this listing.

Literature/general context (not item-specific specifications or medical claims):

• VE-821 is widely cited as a selective small-molecule probe of the ATR (ataxia telangiectasia and Rad3-related) kinase pathway, a central regulator of the DNA damage response to replication stress. ATR signaling modulates checkpoint activation, stabilizes stalled forks, and coordinates DNA repair.
• As a chemical biology tool, VE-821 has been used to study pathway dependencies, synergy with genotoxic stressors, and the interplay between ATR, ATM, and DNA-PKcs signaling networks. Researchers typically assess downstream markers such as phosphorylation state changes and cell-cycle checkpoints to confirm target engagement.
• Biological systems: Employed in cell culture models and biochemical assays to interrogate kinase activity and pathway outcomes. Effective use requires careful titration, timing, and inclusion of orthogonal controls (e.g., genetic knockdown/knockout or alternate inhibitors) to separate on-target from off-target effects.

Caveats:

• Selectivity profiles can be context-dependent and concentration-dependent; confirm with counterscreens.
• No clinical or therapeutic claims are made for this product; it is intended strictly for research use.

Buffer Applications

Not typically applicable. VE-821 is not a buffering agent and is not used to set or maintain pH.

Practical note (general):

• When adding VE-821 DMSO stocks to biological buffers or media, keep final DMSO concentrations low (commonly ≤0.1–0.5%) and constant across conditions to avoid confounding solvent effects.
• Verify compound stability in the chosen buffer over the assay timeframe (e.g., by LC–MS), as adsorption or precipitation can occur with hydrophobic small molecules.

Green Alternatives

Context: VE-821 is a specialized research tool; green considerations pertain mainly to solvent choices for stock preparation and analytics rather than replacement of the active itself.

Greener handling options (general guidance):

• Prefer water/ACN over water/MeOH when feasible for LC due to lower toxicity and improved energy efficiency in drying; however, ACN is petro-derived and subject to supply constraints.
• Explore ethyl acetate for non-aqueous extractions over chlorinated solvents during sample workup (if applicable to your workflow).
• Use microscale assay formats (384/1536-well) to minimize solvent and compound consumption.

Comparison (general; not item-specific):

• DMSO vs NMP/DMF for stock solutions: DMSO is generally preferred for lower toxicity and better biodegradability profile.
• Aqueous-compatible formulations: Incorporating small percentages of PEG400 or cyclodextrins can sometimes reduce DMSO usage; validate for your assay.

Trade-offs:

• Reduced-organic LC methods may increase run times or reduce resolution; balance greenness with data quality.

Note: No greener chemical substitute exists for VE-821’s specific research role; instead, apply green chemistry principles in solvent selection, waste minimization, and energy-efficient storage/handling.

Pharmaceutical Uses

This product is supplied strictly for research use only. No clinical or therapeutic use is implied.

General R&D context (not item-specific specifications):

• Tool compounds like VE-821 are often employed during early discovery as reference standards for target validation, assay development, and exploratory structure–activity relationship work.
• Possible roles in development labs include use as an analytical reference material for LC–MS method development, stability-indicating methods, and impurity profiling within research programs.

Regulatory status and excipient role:

• Not an excipient and not listed for compendial pharmaceutical use in this product entry.
• Any GMP-related application would require separate qualification and documentation; this catalog item is not represented for GMP use.

Documentation:

• For any regulated context, obtain the CoA/SDS for the specific lot and qualify according to internal SOPs. Where pharmacopoeial monographs do not exist, validate in-house methods for identity, purity, and potency as appropriate.

Physical Properties

Item-specific (from Product Data):

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

Literature/general values and guidance (not item-specific specifications):

• VE-821 is commonly supplied as a solid for screening collections and is typically prepared as concentrated stock solutions in anhydrous DMSO for biochemical or cell-based assays (general practice).
• Solubility (literature/general): many kinase-tool compounds show good solubility in DMSO (e.g., 10–50 mM stocks). Aqueous solubility often increases with cosolvent (DMSO) or with minimal amounts of non-ionic surfactant; concrete values should be verified experimentally.
• Melting point, logP/cLogP, pKa, refractive index, density: Not specified for this item; refer to CoA/Spec Sheet and peer-reviewed literature if needed for method development.
• UV-Vis characteristics (general): small-molecule heteroaromatics often exhibit absorbance in the 200–350 nm range; obtain an actual spectrum before using for quantitative UV assays.

Practical notes:

• When preparing analytical methods (HPLC/UPLC), begin with reversed-phase gradients (C18, water/acetonitrile + 0.1% formic acid) and adjust based on observed retention and ionization; confirm identity by MS and/or NMR as appropriate.

Quality and Grades

Item-specific (from Product Data):

• Grade/Purity: Moligand™

What Moligand™ implies (general description; not a specification):

• Moligand™ denotes Aladdin’s small-molecule ligand/library offering geared for discovery and screening workflows. Typical expectations for this grade include suitability for biochemical/biophysical assays and cheminformatics-managed provenance. Exact purity thresholds, analytical methods, and acceptance criteria are item-specific—refer to the CoA/Spec Sheet.

Practical guidance for professionals:

• Verify identity/purity by orthogonal methods appropriate to your application (e.g., HPLC/UPLC with UV and MS detection; NMR as needed). Ensure acceptance criteria meet your internal standards for hit validation or mechanistic studies.
• If ultra-low residual solvents, water content, metals, or UV cutoff are critical for your method, obtain the lot-specific CoA. Values not listed in the Product Data are: Not specified for this item; refer to CoA/Spec Sheet.
• Stabilizers: Not specified for this item; refer to CoA/Spec Sheet. If none are present, consider inert-atmosphere storage for long-term integrity and minimize freeze–thaw cycles of DMSO stocks.

Reaction and Applications

Scope of this product: VE-821 is primarily used as a research tool compound rather than a synthetic reagent.

Item-specific application text: Not provided beyond “For research use only.”

General/literature applications (not item-specific specifications):

• Chemical biology: Employed to probe the ATR-dependent DNA damage response pathway in biochemical or cell-based assays, enabling interrogation of replication stress signaling, checkpoint activation, and pathway cross-talk. Use with orthogonal probes and genetic controls to confirm on-target biology.
• Assay development: Useful in establishing positive controls for ATR-pathway inhibition, benchmarking assay windows, and validating biomarkers (e.g., phosphorylation events) when combined with DNA-damaging agents. Optimize dose and timing empirically.
• Method development: Serves as a reference analyte for LC–MS method qualification in kinase-tool panels, aiding retention-time indexing and ionization optimization.

Practical tips (general):

• Prepare fresh DMSO stocks or aliquot and store frozen to limit degradation. Avoid repeated freeze–thaw.
• Verify activity in your system using appropriate readouts (e.g., biochemical IC50, cellular pathway markers). Include counterscreens to assess selectivity.
• Ensure solvent controls are included at the same DMSO percentage across conditions.

Reaction Conditions

Not typically applicable as a reagent. VE-821 is used as a research tool compound rather than as a substrate, catalyst, or reagent in synthetic transformations.

General handling conditions for use in assays (not item-specific specifications):

• Stock preparation: Dissolve in anhydrous DMSO to a convenient concentration (e.g., 10–50 mM, solubility permitting). Filter if sterile conditions are required.
• Storage/use: Keep on ice during assay setup to reduce degradation in solution; minimize exposure to light if chromophoric.
• Analytical confirmation: Verify concentration by UV or quantitative NMR when critical; confirm integrity by LC–MS.

If employing VE-821 in any chemical transformation studies (uncommon), users should independently establish reactivity, stability, and compatibility, as no reaction-condition guidance is provided for this item.

Safety and Handling

Item-specific (from Product Data):

• 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 Conditions: Store at -80°C (provided).
• Shipping: Shipped with dry ice packs + cold packs (provided).

General laboratory safety (not item-specific; always defer to the SDS):

• Handle in a chemical fume hood; avoid inhalation of dust or aerosols. Prevent skin/eye contact. Use standard PPE: lab coat, safety glasses, and appropriate chemically resistant gloves.
• Avoid ingestion and environmental release. Dispose of waste according to institutional and local regulations.
• Incompatibilities (general): avoid strong oxidizers and strong acids/bases until specific compatibility is known. For DMSO solutions, prevent contact with skin due to enhanced dermal absorption of solutes.
• First aid (general): in case of contact, rinse affected area with water for at least 15 minutes; remove contaminated clothing. If inhaled, move to fresh air. Seek medical attention if symptoms persist.

Notes:

• Because detailed hazard classification is not provided here, consult the product SDS and institutional risk assessments before use. Implement appropriate containment when opening frozen or lyophilized vials to minimize aerosol/particulate exposure.

Solvent Selection

Applicability: VE-821 is typically handled as a solid compound prepared into assay stocks. Solvent selection is primarily relevant to making concentrated stock solutions and for analytical methods.

Item-specific: No solvent recommendations are specified for this item; refer to CoA/Spec Sheet.

General/literature guidance (not item-specific specifications):

• Primary stock solvent: Anhydrous DMSO is commonly used for kinase-focused tool compounds, enabling 10–50 mM stocks depending on solubility. Filter sterilize through 0.2 µm if sterility is required for cell work.
• Working dilutions: Prepare final assay media with ≤0.1–0.5% DMSO (typical ranges in cell assays) to minimize solvent effects; validate for your system.
• Analytical solvents: Water/Acetonitrile (0.1% formic acid) on C18 is a robust starting point for LC; MeOH can be used where compatible.
• Miscibility: DMSO is miscible with water and common organics; premix DMSO stocks with small volumes of media/organic before adding to aqueous buffers to avoid precipitation.

Comparison (general):

• DMSO vs DMF: DMSO generally offers better biocompatibility for cell assays; DMF has stronger odor/toxicity concerns.
• ACN vs MeOH (LC): ACN often affords sharper peaks and lower backpressure; MeOH may improve ionization for some analytes.

Storage and Reconstitution

Item-specific (from Product Data):

• Storage Conditions: Store at -80°C.
• Shipped In: Dry ice packs + Cold packs.

Additional item-specific details:

• Appearance, stabilizers, and exact reconstitution solvent are not specified; refer to CoA/Spec Sheet.

General guidance (not item-specific specifications; implement per your SOPs):

• Upon receipt, keep the container cold. If supplied as a solid, allow to equilibrate in a desiccator to room temperature before opening to prevent condensation. If supplied frozen in solution, keep on dry ice until aliquoted.
• Reconstitution: For small-molecule tool compounds, anhydrous DMSO is commonly used to prepare concentrated stocks (e.g., 10–50 mM subject to solubility). Vortex to dissolve and, if needed, gently warm to room temperature. Avoid aqueous exposure until ready to use to prevent precipitation.
• Aliquoting: Prepare single-use aliquots to minimize freeze–thaw. Store aliquots at -80°C in sealed, inert-atmosphere vials where possible.
• Stability monitoring: Periodically check by LC–MS or HPLC for degradation or precipitation in stored stocks. Protect from light if the compound is photosensitive.

Note: Where exact solvent, concentration limits, or stability data are required, consult the lot-specific CoA/SDS or perform a small-scale pretest.

Structure and Identity

Brief overview: VE-821 is a research small molecule supplied under Aladdin’s Moligand grade, commonly used as a chemical biology tool in DNA damage response research (general literature). Item-specific identifiers are limited in the current listing.

Item-specific (from Product Data):

• Product Name: VE-821
• CAS: 1232410-49-9
• SKU: V408304
• Category: Small molecules and compound libraries (小分子和化合物库)
• InChIKey: Not specified for this item; refer to CoA/Spec Sheet.
• 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.

General/literature context (not item-specific):

• VE-821 is widely cited as a selective ATR pathway probe in chemical biology studies. Structural reports in the literature describe a multi-heterocyclic scaffold optimized for kinase hinge-binding and solvent-exposed substituents; consult primary literature or the CID 51000408 record for exact structure and identifiers.
• 2D structure (literature description): a heteroaromatic core bearing ring nitrogens, with polar tertiary amine/heterocycle features and additional aromatic/amide-like pharmacophore elements designed for kinase active-site engagement. Refer to authoritative databases for definitive depiction.

Notes:

• For definitive structure (SMILES/InChIKey), molecular formula, and exact mass, please consult the CoA/SDS or the referenced CAS/CID databases.

Synthetic Utility

VE-821 is supplied as a finished research tool compound rather than a synthetic intermediate.

General context for medicinal chemistry workflows (not item-specific specifications):

• Can serve as a reference comparator in SAR campaigns targeting the ATR pathway. Use as an external control to benchmark in vitro potency, cellular target engagement, and physicochemical properties.
• Analytical utility: supports calibration/qualification of LC–MS methods and retention-time mapping across kinase-inhibitor panels.
• Derivatization is not typical for catalog material; if analog generation is desired, consult primary literature for disclosed synthetic routes to related scaffolds and perform de novo synthesis under appropriate IP considerations.

Best practices:

• Maintain a stable frozen master stock and generate single-use aliquots to ensure reproducible assay performance.
• Confirm identity and purity of working stocks at critical project milestones (e.g., hit triage, lead optimization checkpoints).

Target Specificity

Item-specific data: Not specified for this item; refer to CoA/Spec Sheet.

Note: Although VE-821 is discussed in the literature in the context of kinase pathway research, this section reports only product-specific validated data, which are not provided here. For assay planning, consult primary literature and perform in-house confirmation of target engagement and selectivity.

Preguntas frecuentes

What is Moligand??

Moligand? is one of Aladdin Scientific's premium product lines, formulated for high-purity applications across multiple workflows. Compared to standard grades in the same workflow, Moligand? products typically offer tighter specifications, more rigorous QC, and stronger lot-to-lot consistency.

How should this product be stored?

Store at ?80 °C. Ultra-low temperature storage is required to maintain the specified shelf life.

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 1232410-49-9, the molecular formula is C18H16N4O3S, and the molecular weight is 368.41 g/mol.

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.