ASK1-IN-3 , CAS No.2426705-19-1

CAS: 2426705-19-1 Cat. No.: A1418213 Fórmula: C₁₈H₁₈N₈O₂ Peso molecular: 378.39

Storage

Store at -20°C

Shipped In

Ice chest + Ice pads

Descripción general

ASK1-IN-3 is a potent and selective ASK1 kinase inhibitor with IC 50 of 33.8 nM, as well as inhibits several cell cycle regulating kinases. ASK1-IN-3 has strong HepG2 cancer cells apoptosis induction and potent cell cycle arrest activities.

Specifications

Condiciones de almacenamiento de almacenamiento

Store at -20°C

Enviado en

Ice chest + Ice pads

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

Tipo de acción

INHIBITOR

Nombres e identificadores

• Peso molecular: 378.39

Application Protocols

No item-specific application protocols are provided for this SKU.

General, non-validated handling guidance for small-molecule tool compounds:

• Stock solution: Prepare in anhydrous DMSO (e.g., 10–50 mM). Aliquot to single-use vials to avoid repeated freeze–thaw and moisture ingress.
• Working solutions: Dilute into pre-warmed assay buffer or culture media with vigorous mixing to the final assay concentration. Keep final DMSO content consistent across samples (commonly ≤0.1–0.5% v/v for cell assays).
• Controls: Include vehicle controls and pathway-relevant positive controls. Verify absence of precipitation (inspect visually and, if critical, by light scattering or filtration) at the working concentration and temperature.
• Documentation: Record lot number, stock concentration, solvent, preparation date, and storage conditions with each experiment to ensure reproducibility.

These are generic best practices and are not product-validated protocols. For detailed, item-specific methods, refer to the CoA/Spec Sheet or peer-reviewed literature once structural/biological data are available for this compound.

Biological Roles

Background (general, literature-level biology; not item-specific claims):

• ASK1 (MAP3K5) is a MAP kinase kinase kinase that integrates cellular stress signals—particularly oxidative stress, ER stress, and inflammatory cytokines—to activate the JNK and p38 MAPK pathways via MKK4/7 and MKK3/6, respectively. This signaling influences apoptosis, autophagy, inflammation, and differentiation in diverse cell types.
• ASK1 activity is tightly regulated by thioredoxin (Trx1/Trx2), 14-3-3 proteins, phosphorylation state, and oligomerization. Reactive oxygen species promote Trx dissociation and ASK1 activation. Upstream inputs include TNF receptor complexes and Toll-like receptors via TRAF adaptors.
• Inhibition of ASK1 is expected to attenuate downstream phosphorylation of JNK/p38 substrates, which can be monitored with phospho-specific immunoassays, transcriptional reporters (AP-1/ATF), or proteomic phospho-signatures. Off-target modulation of related MAP3Ks (e.g., TAK1, MLK family) is a common consideration for small molecules and should be profiled empirically.
• Mitochondrial function, unfolded protein response, and innate immune signaling often intersect with ASK1 control nodes; therefore, context-dependent effects are frequently observed across cell lines and stress paradigms.

This product is labeled by name as an ASK1 inhibitor; however, no potency, selectivity, or cellular activity data are provided in the product record. Researchers should establish concentration-response, time-dependence, and pathway specificity in their own systems using appropriate controls.

Buffer Applications

This product is not a buffering agent and is not used to prepare defined pH buffer systems.

Practical notes for assay buffers (general guidance for small-molecule testing):

• Vehicle control: Match DMSO (or other solvent) concentration in all wells/tubes, typically ≤0.1–0.5% v/v for cell culture, to isolate compound effects from solvent effects.
• Protein binding: Serum proteins and BSA can alter free compound levels. Consider serum-free or defined protein content during acute exposure, or quantify free fraction if needed.
• Adsorption: Hydrophobic compounds may adsorb to plastics. Use low-binding plates and tips, and precondition surfaces if necessary.

Item-specific buffer compatibility and pH stability are not provided; verify stability and absence of precipitation in your chosen assay buffer.

Green Alternatives

Green chemistry considerations are generally framed for solvents and bulk reagents. For a specialized bioactive small molecule like ASK1-IN-3, “green alternatives” are typically not applicable because the compound itself is the variable of biological interest.

Practical greener-practice suggestions (general):

• Minimize DMSO volume: prepare the highest feasible stock concentration consistent with solubility to reduce solvent usage and waste.
• Right-size experiments: use microplate formats and replicate-efficient designs to limit material consumption.
• Waste segregation: collect DMSO- and alcohol-containing liquid waste separately for appropriate disposal.
• Consider greener diluents where scientifically acceptable: aqueous buffers instead of organic media for intermediate dilutions, provided the compound remains in solution.

No structural or synthetic route information is provided for this item; therefore, route redesign, renewable feedstocks, catalyst choices, and PMI/E-factor assessments cannot be evaluated here. If you intend to synthesize analogs, consult green chemistry guidelines for solvent/catalyst selection during route development.

Pharmaceutical Uses

• Regulatory/compendial status: Not specified for this item; refer to CoA/Spec Sheet.
• Intended role: Research-use-only small molecule for laboratory investigation. Not formulated as a drug substance or excipient.

Context (general, non-clinical):

• Compounds described as ASK1 inhibitors are often used as reference tool molecules in discovery-stage studies to probe stress-activated MAPK biology in vitro or in non-clinical models. Such usage focuses on mechanism elucidation and assay control rather than formulation for administration.
• No information is provided for GMP status, impurity profiles per ICH, residual solvent Class 1–3 limits, elemental impurities, or stability studies—requirements that would be essential for pharmaceutical development. This SKU should therefore be used strictly for non-clinical research applications in accordance with the Research Use Only notice.

No therapeutic, diagnostic, or clinical application is implied or supported by this listing.

Physical Properties

Item-specific physicochemical properties have not been disclosed for this SKU.

• Appearance: Not specified for this item; refer to CoA/Spec Sheet.
• Melting point (MP): Not specified for this item; refer to CoA/Spec Sheet.
• Boiling point (BP): Not specified for this item; refer to CoA/Spec Sheet.
• Density: Not specified for this item; refer to CoA/Spec Sheet.
• Solubility: Not specified for this item; refer to CoA/Spec Sheet.
• LogP/logD: Not specified for this item; refer to CoA/Spec Sheet.
• pKa: Not specified for this item; refer to CoA/Spec Sheet.
• Refractive index/UV cut-off: Not specified for this item; refer to CoA/Spec Sheet.

General notes for small-molecule kinase tools (literature-level guidance, not item-specific):

• Many kinase inhibitors are moderately lipophilic and are commonly supplied as solids formulated for dissolution in anhydrous DMSO to prepare concentrated stocks (e.g., 10–50 mM), then diluted into aqueous assay media. Actual solubility and stability are compound-specific and must be verified experimentally for this item.
• If hygroscopicity, polymorphism, or solvates are concerns, verify by Karl Fischer, XRPD, or TGA as applicable. Always defer to the item’s CoA for definitive physical data.

Quality and Grades

• Grade/Purity: Not specified for this item; refer to CoA/Spec Sheet.
• Research Use: For research use only (not for human or veterinary use, clinical diagnostics, or food/cosmetic applications).

How to interpret common grades (general guidance):

• Discovery/Screening grade: intended for in vitro biochemical or cell-based assays; documentation typically focuses on identity, purity by HPLC/UPLC, and MS. Low residual solvents/metals may not be guaranteed unless specified.
• Analytical/Reference standard grade: emphasizes high purity with detailed analytical traceability (qNMR, orthogonal chromatography); used for method development and quantitation.

What to expect and request for this item:

• Identity and purity confirmation data (e.g., HPLC/LC–MS, NMR) should be reviewed in the item’s CoA. If you require specific thresholds (e.g., ≥98% HPLC area), request a lot-specific CoA before purchase.
• Stabilizers, residual solvents, water content, and metal limits: Not specified for this item; refer to CoA/Spec Sheet. If your application is sensitivity-limited (e.g., kinome profiling, cellular phenotyping), specify acceptance criteria at ordering.

Batch-to-batch consistency:

• For structure-activity studies, procure a single lot for a campaign when possible. Retain aliquots of the received lot for cross-checks in future assays.

Reaction and Applications

This product is supplied as a bioactive small molecule intended as a research tool; it is not typically used as a synthetic reagent or catalyst.

• Synthetic reaction role: Not commonly applicable. No item-specific reactivity or functional-group profile has been provided.
• Research applications (general, literature-level context for ASK1 pathway tools):
  • Cell-based signaling studies to interrogate stress-activated MAPK cascades (JNK/p38) downstream of ASK1. Readouts may include phospho-JNK/p38 Westerns, transcriptional reporters (e.g., AP-1), or phenotypic responses to oxidative stress (e.g., H2O2, TNF-α co-stimulation).
  • Biochemical assays to assess kinase activity, binding or thermal stabilization (e.g., ADP-Glo, radiometric kinase assays, CETSA/DSF). Compound-specific potencies, mode of inhibition, or kinome selectivity are not provided for this item and must be established independently.
  • Chemical biology workflows such as time-course inhibition, washout experiments, and combination studies with upstream/downstream pathway modulators to map signaling topology.

Important: Do not infer potency, selectivity, or mechanism for this SKU from its name alone. Validate activity and concentration ranges in your own system. For any reaction chemistry use cases, consult the CoA/Spec Sheet; no functional group or stability data are provided here.

Reaction Conditions

Not applicable as a synthetic reagent: no reaction conditions are defined for this SKU.

Assay usage conditions (general, non-item-specific guidance for small-molecule inhibitors):

• Stock preparation: Dissolve in anhydrous DMSO to a convenient concentration (commonly 10–50 mM), vortex and, if necessary, briefly sonicate. Filter through 0.22 µm PTFE if particulate persists. Verify concentration by UV–Vis or quantitative NMR when precision is required.
• Working concentrations: Determine empirically via concentration–response experiments spanning several logs (e.g., 0.001–30 µM) appropriate to your assay sensitivity. Do not assume potency from the product name.
• Incubation: Preincubation of 15–60 minutes may be used in enzyme or cell assays to reach steady-state target engagement; optimize per system.
• Controls: Include vehicle-only controls, pathway-positive controls (e.g., oxidative stress inducers for ASK1 pathway), and, if available, orthogonal inhibitors to benchmark responses.

These conditions are general literature practices and are not validated for this item. Always document and optimize conditions for your specific system.

Safety and Handling

• GHS classification: Not specified for this item; refer to SDS.
• Signal word / H-statements / Pictograms: Not specified for this item; refer to SDS.

General laboratory precautions (good practice for bioactive small molecules):

• Use in a chemical fume hood. Avoid inhalation, ingestion, and skin or eye contact. Wear appropriate PPE: lab coat, safety glasses, and chemically resistant gloves (e.g., nitrile). Consider double-gloving when handling DMSO solutions due to enhanced dermal transport.
• Avoid aerosols and dust. Use microbalance techniques for weighing to minimize exposure.
• Storage incompatibilities: Absent specific data, segregate from strong oxidizers and acids/bases as a precaution. Keep container tightly closed to limit moisture uptake and oxidative degradation.
• Decontamination: Wipe small spills with absorbent material compatible with the solvent used (e.g., DMSO/ethanol/water), then clean with detergent; dispose according to institutional hazardous waste procedures.
• First-aid overview (refer to SDS for authoritative guidance): rinse eyes/skin with water for ≥15 minutes if exposed; remove contaminated clothing; seek medical attention if symptoms persist; if inhaled, move to fresh air; if ingested, rinse mouth—do not induce vomiting unless directed by medical personnel.

SDS is the authoritative source for hazard classification, exposure limits, and response measures for this item.

Solvent Selection

This product is a bioactive small molecule with no item-specific solubility data provided. The following are general, literature-level practices for small-molecule kinase tool compounds; verify experimentally for this item.

• Primary stock solvent: Anhydrous DMSO is commonly used due to broad solvency and compatibility with biological assays. DMSO is miscible with water and most polar organics, enabling convenient serial dilutions.
• Alternative cosolvents: Ethanol or methanol can be used for initial dissolution when compatible with your assay; however, final vehicle content should typically be kept ≤0.1–0.5% v/v in cell culture to minimize solvent effects. PEG400 or DMF can improve solubility for hydrophobic chemotypes, but may introduce assay artifacts—use cautiously.
• Aqueous media: Direct dissolution into buffers (PBS, HBSS, assay media) is often limited for lipophilic inhibitors. If aqueous delivery is required, consider DMSO pre-dissolution followed by dilution with vigorous mixing, brief sonication, or use of minimal non-ionic surfactant where appropriate. Validate that no precipitation occurs at working concentrations and temperatures.
• Light and moisture: Absent specific data, prepare and store solutions protected from light and moisture to mitigate degradation.

Quick comparison (general):

• DMSO: maximal solvency, biologically tolerated at low %; may enhance dermal absorption.
• Ethanol: good solvency, volatile; limited tolerance in cells.
• PBS/Water: best biological compatibility; limited direct solvency for hydrophobic compounds.

Always confirm solvent choice, concentration, and vehicle effects empirically for this item.

Storage and Reconstitution

• Storage (from product data): Store at -20°C. Shipments are dispatched in an ice chest with ice pads to maintain a cold chain.
• Appearance: Not specified for this item; refer to CoA/Spec Sheet.

General reconstitution guidance for small-molecule inhibitors (not item-specific):

• Upon receipt: Allow the sealed container to equilibrate to room temperature before opening to prevent moisture condensation. If provided as a solid, confirm mass on a calibrated microbalance.
• Solubilization: Dissolve in anhydrous DMSO to prepare a concentrated stock (commonly 10–50 mM, limited by actual solubility). Mix thoroughly; brief bath sonication can aid dissolution. If necessary, warm gently to 25–37°C, avoiding prolonged heating.
• Aliquoting: Dispense into small, single-use aliquots in inert vials (amber, low-bind) to minimize freeze–thaw and adsorption losses. Flush headspace with inert gas if air sensitivity is suspected.
• Storage of solutions: Store frozen at -20°C or below. Protect from light and moisture. Avoid repeated freeze–thaw; thaw on ice and use promptly.
• Stability: Not specified for this item; refer to CoA/Spec Sheet. Establish in-house stability/solubility and precipitation checks at intended working concentrations in your assay media.

Always refer to the SDS and lot-specific CoA for definitive handling and storage instructions.

Structure and Identity

ASK1-IN-3 (SKU: A1418213) is cataloged as a small-molecule research tool named for putative inhibition of apoptosis signal–regulating kinase 1 (ASK1/MAP3K5). Item-specific structural identifiers are not provided.

• CAS: 2426705-19-1
• Molecular formula: Not specified for this item; refer to CoA/Spec Sheet.
• Molecular weight: Not specified for this item; refer to CoA/Spec Sheet.
• SMILES: Not specified for this item; refer to CoA/Spec Sheet.
• InChIKey: Not specified for this item; refer to CoA/Spec Sheet.

Structural features (general context):

• No 2D/3D structure is provided in the product data for this item. Many ASK1-focused tool compounds in the literature are heteroaromatic kinase-directed scaffolds (e.g., biaryl or bicyclic heterocycles with H-bond donor/acceptor motifs), but the structure of ASK1-IN-3 in this listing is not disclosed and should not be inferred.

How to reference: cite the CAS and SKU exactly as above; consult the Certificate of Analysis (CoA) for definitive identifiers when available.

Synthetic Utility

This SKU represents a finished bioactive small molecule intended for use as a research tool, not as a synthetic building block.

• Functional-group participation: Not specified for this item; no structural information is provided to evaluate reactivity, protection/deprotection strategies, or compatibility with common transformations.
• Use in synthesis: Not typically applicable. Without a disclosed structure, proposing cross-couplings, heteroatom substitutions, or late-stage derivatizations would be speculative and is not recommended.

If your objective is to prepare analogs or SAR series around ASK1 inhibition:

• Obtain or determine the structure and functional groups via literature/patents or vendor documentation, then plan convergent routes with heteroaryl couplings (e.g., Suzuki, Buchwald–Hartwig) or amide formations as appropriate to the scaffold (general approaches seen in kinase inhibitor chemistry). Ensure you independently verify structure and purity (NMR, HRMS, HPLC) and assess physicochemical properties driving solubility and permeability.

For this specific item, consult the CoA/Spec Sheet for any available identity data; absent that, treat it solely as a biological probe compound.

Target Specificity

• Product name suggests: ASK1 inhibitor (MAP3K5). However, no item-specific target validation, potency (IC50/Ki), mode of inhibition, or kinome selectivity data are provided in the product record.

Guidance:

• Treat this compound as a putative ASK1-pathway tool pending independent confirmation. Perform target engagement assays (e.g., biochemical kinase assay, NanoBRET/ CETSA in cells) and off-target profiling as needed for your application.
• Consult the lot-specific CoA/Spec Sheet or primary literature for any available characterization. Do not rely on nomenclature alone for specificity claims.