Delgocitinib ethanolate , CAS No.2064338-33-4

CAS: 2064338-33-4 Cat. No.: D1428683 Formule: C₁₈H₂₄N₆O₂ Poids moléculaire: 356.42

Storage

Store at -20°C

Shipped In

Ice chest + Ice pads

Vue d’ensemble

Delgocitinib ethanolate is a specific JAK inhibitor with IC 50 s of 2.8, 2.6, 13 and 58 nM for JAK1 , JAK2 , JAK3 and Tyk2 , respectively.

Specifications

Conditions de stockage de stockage

Store at -20°C

Expédié en

Ice chest + Ice pads

Ce produit nécessite l'expédition en chaîne froide. Les services terrestres et autres services économiques ne sont pas disponibles.

Noms et identifiants

Poids moléculaire

356.42

Application Protocols

General research-use guidance (non-item-specific; adapt to your system)

• Stock preparation

  • Dissolve in DMSO to 10 mM. Vortex and, if needed, sonicate briefly. Filter through 0.22 µm PTFE to remove particulates. Aliquot and store at -20°C to minimize freeze–thaw cycles.
  • If ethanol is preferred, prepare 5–10 mM stocks and use promptly due to volatility; seal containers well.

• Biochemical kinase assay (example workflow)

  • Combine kinase, substrate, ATP (near Km), buffer (e.g., HEPES pH 7.5, Mg2+), and serially diluted compound (constant vehicle, typically 0.1–0.5% DMSO).
  • Incubate 30 minutes at 25–30°C; detect product via ADP-Glo, TR-FRET, or ELISA. Fit dose–response to obtain IC50.

• Cellular pSTAT assay (example workflow)

  • Preincubate cells with compound for 1 hour; stimulate with cytokine for 10–20 minutes; lyse and quantify phospho-STAT by Western blot or sandwich ELISA.
  • Include vehicle control and an orthogonal JAK inhibitor as a positive control.

• Stability checks

  • Assess freeze–thaw stability by LC–MS. Verify no precipitation upon dilution into assay media over the assay timeframe.

Note: These are general protocols. Item-specific solubility, purity, and form (ethanolate) are not specified here; consult the CoA and SDS.

Biological Roles

Context (literature; research only)

• Pathway: Delgocitinib is described in the literature as a potent pan-Janus kinase (JAK) inhibitor affecting the JAK–STAT signaling cascade. The JAK family (JAK1, JAK2, JAK3, TYK2) transduces cytokine receptor signals, culminating in STAT phosphorylation, dimerization, and transcriptional regulation.
• Mechanistic theme: Small molecules in this class commonly bind the ATP site and engage the kinase hinge region via heteroaromatic hydrogen-bonding, with substituents occupying adjacent hydrophobic pockets.
• Cellular readouts: Modulation is typically monitored by reductions in phospho-STAT levels (e.g., pSTAT1/3/5) downstream of cytokine stimulation, changes in reporter gene activity, or phenotypic responses consistent with altered cytokine signaling.
• Selectivity considerations: Reported as pan-JAK in many studies; however, selectivity windows versus other kinases and within the JAK family depend on assay conditions (ATP concentration, protein construct, and cellular context). Complementary chemoproteomics or kinome profiling is recommended to map off-targets.

Important notes

• This product is for research use only. No therapeutic, diagnostic, or clinical claims are made or implied.
• Assay design should include appropriate cytokine stimuli, time-course optimization for STAT phosphorylation, and counter-screens to decouple general cytotoxicity from on-target pathway effects.

Buffer Applications

Not typically applicable. Delgocitinib ethanolate is a small-molecule inhibitor rather than a buffering reagent. It does not serve as a pH buffer system.

Practical note

• When introducing delgocitinib into buffered biological media, maintain consistent co-solvent (e.g., DMSO or ethanol) percentages across all wells or samples to avoid differential precipitation or vehicle effects.
• Verify compatibility with common assay buffers (e.g., HEPES, PBS) by conducting small-scale solubility and stability checks at the intended working concentration and temperature.

Green Alternatives

While delgocitinib ethanolate itself is a fixed structure, greener choices can be made around its handling and dissolution.

Greener solvent strategy (general)

• Aqueous-compatible stocks: Where assay design allows, use minimal DMSO (≤0.1–0.2% v/v final) by preparing higher-concentration stocks and microvoluming.
• Prefer ethanol over methanol where feasible due to lower toxicity, recognizing solubility tradeoffs and volatility.
• Consider biobased solvents for preparative cleaning steps (e.g., bio-ethanol) and minimize chlorinated solvent use.

Comparison (general)

• DMSO: High solvency; low volatility; favorable EHS profile relative to many aprotic polar solvents but may affect cells at higher %.
• Ethanol: Renewable, rapidly biodegradable; flammable; may limit achievable aqueous concentrations.

Operational practices

• Right-size aliquots to reduce waste from thawed/expired solutions.
• Employ microscale assays and high-density plate formats to reduce total solvent consumption.

Note: No item-specific EHS metrics are provided. Always follow institutional green chemistry policies and validate that greener solvent substitutions preserve assay performance.

Pharmaceutical Uses

Scope

• For research use only. Not for human or veterinary use, clinical administration, or diagnostic procedures.

Relevant research-oriented uses

• Reference standard: May be used as a reference material in analytical method development, forced-degradation studies, and stability-indicating LC–MS methods, particularly to differentiate free base vs. ethanolate forms.
• Preformulation studies: Solvate characterization (ethanol content by TGA/GC, desolvation temperature by DSC) and polymorph screening to understand solid-state behavior relevant to formulation science.
• In vitro ADME: Suitable for research into solubility profiling (shake-flask), microsomal stability, plasma protein binding, and permeability assays under GLP-like but non-clinical settings.

Notes on solvates

• Ethanolates may show different hygroscopicity, equilibrium solubility, and compaction properties compared to anhydrous forms. If translating data to other forms, adjust for free-base equivalence using the CoA assay of solvent content.

Regulatory status

• No pharmacopeial monograph information is provided for this item. For any regulated work, source or qualify materials per applicable guidelines and use certified reference standards where required.

Physical Properties

Item-specific properties

• Appearance: Not specified for this item; refer to CoA/Spec Sheet.
• Melting point (MP): Not specified for this item; refer to CoA/Spec Sheet. Note: solvate forms may show broadened or multi-step thermal events due to ethanol loss.
• Boiling point (BP): Not applicable to this solid at ambient pressure; decomposition/solvate desolvation may precede boiling.
• Density: Not specified for this item; refer to CoA/Spec Sheet.
• Solubility: Not specified for this item; refer to CoA/Spec Sheet.
• LogP, pKa, refractive index: Not specified for this item; refer to CoA/Spec Sheet.

General/literature guidance (non-specification)

• Delgocitinib free base is commonly prepared as DMSO stock solutions for biochemical and cell-based assays due to high solvating power and stability; ethanol and methanol are frequently miscible co-solvents for intermediate stocks. Final assay media typically contain ≤0.1–0.5% DMSO (v/v).
• Solvate forms can exhibit distinct apparent solubility and hygroscopicity relative to the anhydrous base; gentle drying can cause partial desolvation and phase change. Use the exact lot’s CoA for authoritative values.
• Thermal behavior: ethanol solvates often show endotherms near the ethanol loss temperature (Tdesolvation), followed by a distinct melt for the desolvated phase—DSC/TGA recommended if thermal processing is planned.

Quality and Grades

Item specifics

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

Context and implications

• Research-use grade: Provided for research use only (per item data). Not for human or veterinary use, diagnostics, or clinical applications.
• Purity reporting: For small-molecule inhibitors, purity is typically assessed by HPLC/UPLC with orthogonal ID (MS/NMR). When available, review chromatographic purity, residue solvents (especially ethanol for solvates), and water content (KF) on the CoA.
• Solvate verification: Ethanol stoichiometry (e.g., x·EtOH) may be supported by 1H NMR integration, TGA weight loss, or elemental analysis. Minor lot-to-lot variation in solvate content can occur; dosing by free-base equivalence may require correction using the CoA assay value.
• Stabilizers: None stated for this item. If stabilizers are present in a given lot, they will be listed on the CoA and may affect spectral baselines and assay interference.

Best practices

• For screening campaigns, document lot number and purity basis (area% vs. weight%) to ensure reproducibility.
• If quantitative SAR is required, consider standardizing to free-base content (assay-corrected) rather than bulk weight of solvate.

Reaction and Applications

This product is supplied as a research small molecule for screening, target engagement studies, and reference/control work, not as a synthetic reagent. Consequently, it is not typically deployed to promote or mediate synthetic reactions.

Research applications (general, literature)

• Enzymology: Investigations of the JAK–STAT signaling axis; enzyme inhibition assays against JAK family kinases (JAK1/2/3) and TYK2 to determine IC50/Ki values under defined ATP conditions.
• Chemical biology: Probe for pathway modulation, phospho-STAT readouts, target engagement (e.g., CETSA, NanoBRET), and off-target profiling (kinome panels).
• Analytics: Reference standard in LC–MS method development, stability-indicating methods, and solvate characterization (TGA/DSC for ethanol content).

Practical notes

• Prepare concentrated DMSO stocks and aliquot to minimize freeze–thaw cycles. Use low-binding consumables when working at low nM–µM concentrations.
• Control compounds: Include orthogonal JAK inhibitors with distinct chemotypes to validate assay specificity and mitigate chemotype-specific artifacts.
• ATP-competitive behavior (literature): Expect assay sensitivity to ATP concentration; report Km,ATP and maintain consistent ATP levels across runs.

For synthetic chemistry use-cases, see the Synthetic Utility section for general considerations (limited applicability to this item).

Reaction Conditions

Not applicable in the conventional synthetic sense. This product is not intended as a reagent or catalyst.

Assay conditions (general, literature) for research use

• Enzyme inhibition: Typical kinase assays are run at 25–37°C with ATP near Km,ATP for the specific JAK isoform; reaction times 10–60 minutes; readouts via luminescent ADP detection or phospho-specific antibodies.
• Cellular assays: Pretreat cells with compound (e.g., 0.5–2 hours), stimulate with cytokine (e.g., IFN-α/γ, IL-2/6) for 10–30 minutes, then quantify phospho-STAT levels via Western blot, ELISA, or high-content imaging.
• Concentration ranges: Titrate across ≥10-point half-log serial dilutions spanning sub-nanomolar to low micromolar to capture full dose–response; maintain constant vehicle percentage across conditions.

These conditions are general literature guidance and are not item-specific specifications. Optimize for your system and consult the SDS/CoA for handling constraints.

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 and pictograms: Not specified for this item; refer to SDS.

General laboratory precautions (non-binding guidance; defer to SDS)

• PPE: lab coat, safety glasses, and appropriate gloves (e.g., nitrile). Handle solids in a fume hood or ventilated enclosure to avoid dust/aerosol generation.
• Avoid exposure: prevent inhalation, ingestion, and skin/eye contact. Wash thoroughly after handling.
• Incompatibilities: strong oxidizers and strong acids/bases may degrade nitrogen-rich heteroaromatics; avoid elevated heat that may drive desolvation and dusting.
• First aid (overview): in case of skin/eye contact, rinse with water for at least 15 minutes; if inhaled, move to fresh air; if ingested, seek medical attention. Always consult the SDS for the definitive measures.
• Spill response: avoid dust; gently cover and collect with inert absorbent; dispose in accordance with institutional and local regulations.
• Special note for solvates: heating can release ethanol vapors—ensure adequate ventilation and eliminate ignition sources during thermal processing or lyophilization.

Shipping and storage

• Shipped: Ice chest + ice pads (per item data).
• Storage: Store at -20°C (per item data). Keep tightly closed, desiccated, and protected from light to minimize solvent loss and polymorphic change.

Solvent Selection

Applicability: As a neutral/weakly basic, nitrogen-rich heteroaromatic small molecule, delgocitinib ethanolate is typically handled as DMSO or alcohol stock solutions for biochemical and cell-based assays (research use only).

General guidance (literature/practice)

• Primary stock solvent: DMSO offers high solvating power and stability. Typical stock concentrations: 1–10 mM; filter-sterilize if needed using PTFE/RC membranes.
• Alternative solvents: ethanol or methanol can be used for intermediate stocks; aqueous buffers often require co-solvent (e.g., 0.1–1% DMSO or EtOH) to prevent precipitation.
• pH considerations: Avoid strong acid/base in final media unless solubility profiling indicates benefit; excessive protonation/deprotonation can alter target engagement and cell permeability.
• Miscibility profile: DMSO is miscible with water and polar organics; ethanol is miscible with water and most organics. When spiking into aqueous systems, add stocks slowly with vigorous mixing to prevent local supersaturation.

Comparison (general)

• DMSO vs ethanol: DMSO maximizes solubility but can influence cell physiology at >0.5% v/v; ethanol is more volatile and often limited to ≤0.1–0.5% v/v in biological assays. Choose based on assay tolerance and required concentration.

Note: Item-specific solubility is not provided; confirm solvent choice and limits empirically and consult the CoA.

Storage and Reconstitution

Item-specific conditions

• Storage temperature: Store at -20°C (per item data).
• Shipping: Ice chest + ice pads (per item data).

Handling guidance

• Keep container tightly closed in a desiccated environment. Protect from light. Minimize headspace to reduce ethanol loss from the solvate and avoid polymorphic transitions.
• Allow vial to equilibrate to room temperature in a desiccator before opening to prevent moisture condensation.

Reconstitution (general)

• For analytical or assay use, prepare concentrated stocks in anhydrous DMSO (e.g., 10 mM). If using ethanol, note increased volatility and potential for concentration drift; record preparation time and store in crimped vials if possible.
• After reconstitution, aliquot into single-use portions to avoid repeated freeze–thaw. Store aliquots at -20°C. Thaw at ambient temperature and mix thoroughly before use.

Stability and monitoring

• Inspect visually for particulates or precipitation upon dilution. If necessary, clarify by brief centrifugation and use the supernatant.
• For long-term projects, periodically confirm identity and purity by LC–MS/HPLC. Monitor for changes indicative of desolvation or degradation.

Note: If the CoA provides free-base equivalence or ethanol content, use those values to calculate exact dosing concentrations. Always refer to the SDS/CoA for authoritative stability and handling details.

Structure and Identity

Overview: Delgocitinib ethanolate is the ethanol solvate form of the small-molecule Janus kinase (JAK) inhibitor delgocitinib (research-use only). As a solvate, its exact elemental composition and mass differ from the anhydrous free base.

Item-specific identifiers

• CAS: 2064338-33-4
• 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, literature)

• Compound class: nitrogen-rich heteroaromatic small molecule; reported pan-JAK inhibitor (JAK1/2/3 and TYK2) in the JAK–STAT pathway literature.
• Functional motif: typically features fused aza-heterocycles optimized for ATP-binding site engagement in kinases; ethanolate indicates 1:1 or non-integer ethanol inclusion in the crystal lattice (stoichiometry may vary by lot—see CoA).
• Solid-state form: ethanol solvate can modify crystallinity, melting behavior, and apparent solubility versus the free base; these attributes are formulation- and lot-dependent.

2D description (general)

• Delgocitinib core comprises multiple ring nitrogens and H-bond acceptors consistent with kinase hinge-binding; pendant substituents occupy hydrophobic pockets. The ethanolate does not alter covalent connectivity of the API core, but co-crystallized ethanol participates in lattice hydrogen-bonding.

Synthetic Utility

Limited applicability. Delgocitinib ethanolate is a finished small-molecule inhibitor supplied for research use, not a building block or reagent.

General medicinal chemistry perspective (literature)

• Structural theme: Kinase hinge-binding heteroaromatics illustrate strategies for ATP-competitive inhibition (e.g., bidentate H-bonding patterns, vectoring into selectivity pockets).
• Learning tool: Can inform SAR hypotheses regarding nitrogen positioning, ring fusion patterns, and substituent effects on solubility and selectivity.
• Analytical benchmarking: Useful as a control to validate kinase assay platforms, establishing dynamic range and system suitability.

If derivatization is attempted for probe development

• Bioconjugation handles, if engineered synthetically, should preserve hinge-binding pharmacophore; linkers are commonly placed on solvent-exposed vectors identified by co-crystal structures (general guidance; not specific to this molecule without structural data).
• Maintain awareness that modifications can substantially alter selectivity and permeability; comprehensive re-profiling is required.

Target Specificity

Item-specific target data are not provided. The following reflects general literature for delgocitinib (research use only):

• Primary targets (literature): Janus kinases JAK1, JAK2, JAK3, and TYK2 (pan-JAK profile). Reported as ATP-competitive with hinge-binding interactions typical of kinase inhibitors.
• Selectivity considerations: Off-target activity may appear within the broader kinome depending on assay format and ATP concentration. Cross-screening against a kinase panel and testing in orthogonal biochemical and cellular assays are recommended.
• Pathway biomarkers: Decreases in STAT phosphorylation (e.g., pSTAT1/3/5) upon cytokine stimulation serve as proximal biomarkers of target engagement.

Note: For any quantitative potency, selectivity ratios, or kinetic parameters, consult primary literature and generate in-house confirmation under your assay conditions. No numerical specificity data are supplied with this item.

Foire aux questions

How should this product be stored?

Store at ?20 °C. Freezer storage is required to maintain the specified shelf life.

How is this product shipped?

This product ships in an insulated container with ice pads. Unpack on arrival and transfer it to the storage condition stated above.

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

The CAS Number is 2064338-33-4, the molecular formula is C18H24N6O2, and the molecular weight is 356.42 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.