PROTAC AKR1C3 degrader-1 , CAS No.P1438688

CAS: P1438688 Cat. No.: P1438688 Summenformel: C₄₅H₄₃N₇O₁₀ Molekulargewicht: 841.86

Storage

Store at -20°C

Shipped In

Ice chest + Ice pads

Übersicht

PROTAC AKR1C3 degrader-1 (compound 5) is a potent AKR1C3 PROTAC degrader. PROTAC AKR1C3 degrader-1 decreases the protein expression of AKR1C3, AKR1C1/2, and ARv7. PROTAC AKR1C3 degrader-1 has the potential for the research of prostate cancer. (Blue:ubiquitin E3 ligase cereblon ligand , Black: linker ; Pink: AKR1C3 inhibitor ).

Spezifikationen

Storage

Store at -20°C

Verschickt in

Ice chest + Ice pads

Dieses Produkt erfordert Kühlkettenversand. Grundversand und andere Economy-Optionen sind nicht verfügbar.

Aktionsart

DEGRADER

Namen und Kennungen

Molekulargewicht

841.86

Application Protocols

No tested applications, assay conditions, or recommended dilutions are provided in the Product Data for this item.

• Validated applications: Not specified for this item; refer to CoA/Spec Sheet.
• Recommended working concentrations, incubation times, or positive control cell lines: Not specified for this item; refer to CoA/Spec Sheet.

Guidance (general, non-binding):

• Establish baseline AKR1C3 expression in your system.
• Titrate compound across a log-scale concentration range with consistent DMSO content.
• Assess degradation by Western blot or quantitative immunoassay at multiple time points.
• Include mechanistic controls (proteasome/neddylation inhibitors) and negative controls (inactive analog or vehicle).

Because protocols must be tailored to cell type and assay platform, please validate conditions locally and consult any forthcoming technical notes associated with your specific lot.

Biological Roles

Scope: This section summarizes general, literature-based biology pertinent to AKR1C3 and the PROTAC modality. It does not describe item-specific performance.

• AKR1C3 (aldo-keto reductase family 1 member C3): A NADPH-dependent oxidoreductase involved in steroid hormone metabolism (e.g., reduction of androgens/estrogens intermediates) and prostaglandin conversion (e.g., PGD2→11β-PGF2α). It can influence cellular signaling by modulating local concentrations of bioactive steroids and prostaglandins.
• Cellular localization: Predominantly cytosolic; expression varies across tissues and cell lines.
• Chemical biology rationale: Degrading AKR1C3, rather than only inhibiting it, can eliminate both catalytic activity and any nonenzymatic scaffolding functions, enabling acute functional interrogation.
• PROTAC mechanism (general): Bifunctional degrader simultaneously binds the target protein (AKR1C3) and an E3 ubiquitin ligase, promoting proximity-driven ubiquitination and subsequent proteasomal degradation. Key outcomes assessed experimentally include degradation potency (e.g., DC50), maximal degradation (Dmax), time-to-degradation, and recovery dynamics upon washout (literature concepts; not item-specific data).
• Selectivity considerations: Off-target degradation may result from off-target binding or E3 subcellular distribution. Proteome-wide profiling and counter-screens are standard to characterize selectivity.

Note: Biological roles and phenotypes observed upon AKR1C3 degradation depend on cell type, expression levels, and compensatory pathways. Use appropriate controls (inactive analogs, E3 competition) to establish causality.

Buffer Applications

This product is not a classical buffer reagent. However, buffers are integral to its use in biochemical and cell-based assays.

General buffer guidance for degrader studies (not item-specific):

• Stock preparation: Dissolve compound in DMSO to a concentrated stock. For working solutions, dilute into pre-warmed assay buffer or complete cell culture media with vigorous mixing to avoid precipitation. Keep final DMSO low (commonly ≤0.1–0.5% v/v, as permitted by the system).
• Lysis buffers: For endpoint quantification of AKR1C3 levels, RIPA-like buffers or milder NP-40 buffers with protease/phosphatase inhibitors are common prior to Western blotting or capillary immunoassay.
• Stability considerations: Avoid prolonged incubation in highly basic buffers if ester linkers are suspected; protect from light if the compound is light-sensitive (item-specific data not provided).
• Additives: Small amounts of nonionic surfactant (e.g., 0.01–0.05% Tween-20) can reduce adsorption to plastics. Serum proteins can aid solubilization but may bind the compound; maintain consistent protein content across conditions.

Item-specific buffer compatibility and pH stability: Not specified for this item; refer to CoA/Spec Sheet.

If your workflow requires exact buffer recipes, titration ranges, or compatibility with specific salts/chelators, please validate empirically and consult the SDS/CoA for any available solubility/stability notes.

Green Alternatives

As a specialized research probe, the main environmental footprint of a PROTAC study arises from solvent use, consumables, and assay scale rather than the degrader itself.

Greener handling strategies (general guidance):

• Solvent minimization: Use high-concentration DMSO stocks and miniaturize assays (96- to 384-well) to reduce overall solvent consumption.
• Prefer benign co-solvents: Where possible, favor aqueous buffer with minimal DMSO (≤0.1–0.2% v/v) over DMF/NMP. Ethanol or 2-propanol can serve as short-term co-solvents but verify assay tolerance.
• Closed systems: Employ sealed microplates to limit evaporative losses and exposure.
• Waste segregation: Collect DMSO- and DMF-containing waste separately for appropriate disposal; avoid halogenated solvents unless required by analytics.

Comparison (general; not item-specific):

• DMSO vs DMF/NMP: DMSO typically presents a better EHS profile for bioassays and is more readily accepted in green chemistry metrics.
• Aqueous vehicles: Use serum-containing media or protein supplements to enhance apparent solubility and reduce organic solvent fractions.

Trade-offs:

• Surfactants and proteins can complicate downstream analytics (e.g., LC–MS ion suppression). Balance greener diluents with analytical requirements.

Note: No alternative “green” degrader is specified for this target in the product data. Users can nonetheless implement greener assay designs and solvent stewardship.

Pharmaceutical Uses

This product is supplied strictly for research use only. No clinical, diagnostic, or therapeutic applications are claimed or supported.

Context (general, non-clinical):

• Role in discovery research: PROTAC degraders are employed as chemical probes to study target biology in vitro and in cellular systems, and can inform medicinal chemistry campaigns focused on targeted protein degradation.
• Formulation relevance: In preclinical research settings, solubility and stability screening may explore co-solvent systems, nanoparticles, or cyclodextrins. Such activities are research-only and are not specifications for this item.
• Pharmacopoeia/compendial status: Not applicable; no pharmacopeial monograph is implied for this research reagent.

Item-specific information:

• Excipient status, dosage form compatibility, and GMP attributes: Not specified for this item; refer to CoA/Spec Sheet.

Any translation of this compound to regulated applications would require separate sourcing, qualification, and regulatory review not covered by this catalog entry.

Physical Properties

Item-specific physicochemical data are not provided in the product data for PROTAC AKR1C3 degrader-1.

• Molecular Weight: Not specified for this item; refer to CoA/Spec Sheet.
• Molecular Formula: Not specified for this item; refer to CoA/Spec Sheet.
• Appearance: Not specified for this item; refer to CoA/Spec Sheet.
• Melting Point: Not specified for this item; refer to CoA/Spec Sheet.
• Boiling Point: Not applicable/unknown for this class; PROTACs are typically nonvolatile solids (literature, general).
• Density/Refractive Index: Not specified for this item; refer to CoA/Spec Sheet.
• Solubility: Not specified for this item; refer to CoA/Spec Sheet.

General PROTAC trends (literature context, not item-specific specifications):

• Solubility: Frequently soluble in polar aprotic organic solvents such as DMSO or DMF; aqueous solubility is often limited and may benefit from co-solvents (e.g., DMSO→buffer serial dilution) or surfactant-containing media.
• LogP and polarity: Bifunctional design often produces high polar surface area with moderate-to-high lipophilicity; permeability can be variable and may be formulation-dependent.
• Stability: Many PROTACs are stable when stored dry at −20°C, protected from moisture and light; hydrolytic and oxidative liabilities depend on linker chemistry (e.g., ester vs amide vs PEG linkers).

Important: For experimental planning, consult the actual CoA/SDS for this catalog item for any available numeric data and solvent/dissolution recommendations.

Quality and Grades

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

Context and interpretation:

• Research-use compounds like PROTAC degraders are typically supplied at high chemical purity suitable for biochemical and cell-based studies, but specific assay suitability (e.g., LC–MS, in-cell Western, proteomics) depends on impurity profile and stabilizer content. Because no explicit grade (e.g., ≥98%, HPLC, bioactive grade) is given here, please consult the CoA for the batch-specific purity, analytical method (HPLC/UPLC), and residual solvent levels.
• Stabilizers/antioxidants: Not specified for this item; refer to CoA/Spec Sheet. If present, stabilizers can influence UV baselines and bioassay backgrounds; remove if incompatible with your assay (e.g., by preparative purification) or account for them in controls.
• UV cutoff, water content, metal limits: Not specified for this item; refer to CoA/Spec Sheet.

Best practices for quality verification (general guidance):

• Confirm identity and purity by orthogonal methods (e.g., LC–MS, HRMS, NMR) upon receipt if your workflow requires stringent qualification.
• For quantitative cell assays, standardize DMSO content across wells and include vehicle controls. If degradation data will be compared across lots, maintain consistent storage and thawing practices to minimize lot-to-lot variability.

Reaction and Applications

This product is a chemical biology tool rather than a reagent for synthetic transformations. Consequently, classical organic reactions (e.g., Grignard, cross-coupling) do not apply. Instead, its applications center on targeted protein degradation.

Applications in research (general for AKR1C3-directed PROTACs; not item-specific claims):

• Mechanistic studies: Probe the role of AKR1C3 in cellular pathways by induced degradation rather than inhibition, enabling temporal control and differentiation from catalytic inhibition phenotypes.
• Target validation: Compare genetic knockdown/knockout to small-molecule-induced degradation to assess on-target biology.
• Chemical proteomics: Quantify degradation of AKR1C3 and possible off-targets by TMT-based LC–MS/MS after compound treatment.
• Degradation kinetics: Time-course studies (e.g., 0.5–24 h) monitoring AKR1C3 levels by Western blot or capillary immunoassay to derive Dmax and t1/2,deg (literature parameters, not item-specific).
• SAR exploration: Evaluate how linker length/composition or E3 selection (if analogs are available) modulates potency and selectivity.

Practical considerations:

• Employ matched controls such as the target binder alone, the E3 ligand alone, and an inactive stereoisomer if available.
• Validate proteasome dependence using MG132 or similar; include neddylation inhibitor (e.g., MLN4924) controls to confirm CRL involvement when appropriate.
• Optimize dosing to minimize cytotoxicity unrelated to target degradation; standardize DMSO content across conditions.

Manufacturer Applications: Not provided in Product Data; users should design studies consistent with research-use-only status.

Reaction Conditions

Classical chemical reaction conditions are generally not applicable because this product is a targeted degrader used in biological systems, not a reagent for synthesis.

Instead, researchers often consider biological assay conditions (general guidance; not item-specific):

• Dosing range: Start with a broad range (e.g., low nM to low μM) to capture degradation windows; maintain constant vehicle content (DMSO).
• Exposure time: Perform time-course experiments (e.g., 0.5, 2, 6, 24 h) to characterize onset and durability of degradation.
• Controls: Include proteasome inhibition (e.g., MG132) or neddylation inhibition to verify UPS dependence; include warhead-only and E3-ligand-only controls where available.
• Readouts: Western blotting, capillary immunoassay, targeted proteomics, or reporter assays to quantify AKR1C3 levels.
• Cell system selection: Choose lines with measurable AKR1C3 expression; verify by baseline Western or qPCR prior to degrader studies.

Item-specific chemical stability, solution half-life, or degradation kinetics are not provided in the product data and should be determined empirically or obtained from the CoA/Spec Sheet if available.

Safety and Handling

Authoritative safety information should be taken from the item SDS. The following summarizes what is known from the listing and general best practices for PROTAC small molecules.

• GHS Classification: Not specified for this item; refer to SDS.
• Signal Word / H-Statements / Pictograms: Not specified for this item; refer to SDS.
• Storage Conditions (item-specific): Store at −20°C.
• Shipping (item-specific): Shipped in ice chest with ice pads to maintain cold chain.

General laboratory precautions (not item-specific):

• PPE: Lab coat, safety glasses, and appropriate chemical-resistant gloves (e.g., nitrile). Handle powders/solutions in a chemical fume hood to minimize exposure.
• Avoid ingestion, inhalation, and skin contact. PROTACs are typically nonvolatile, but dust generation should be minimized.
• Incompatibilities: Avoid strong oxidizers and strong acids/bases until specific stability data are known for the item. Protect from moisture if supplied as a dry solid; avoid prolonged exposure to elevated temperatures.
• First aid (general): In case of contact, rinse affected area with water; seek medical attention if irritation persists. If inhaled, move to fresh air. If ingested, rinse mouth; obtain medical attention.
• Spill/cleanup: Use inert absorbent for solutions. For solids, gently dampen to avoid dust, collect mechanically, and dispose of according to institutional and local regulations.

Note: Degraders are potent biological tools; use caution to avoid unintended exposure in cell culture areas. Always defer to the SDS for definitive hazard and response information.

Solvent Selection

Item-specific solubility data are not provided. The following guidance is general for PROTAC degraders and should be validated empirically for this item.

• Primary stock solvent (general): DMSO is the most common due to broad solvency for heterobifunctional molecules and compatibility with biological assays at low v/v%.
• Alternative solvents: DMF and NMP can dissolve challenging PROTACs but may be less desirable biologically. Ethanol or isopropanol can be partial co-solvents. Aqueous buffers often require DMSO-assisted dilution.
• Miscibility and dilution: Prepare a concentrated DMSO stock (e.g., 10–50 mM, if soluble), then serially dilute into assay buffer or media, keeping final DMSO ≤0.1–0.5% v/v as your biology permits. Pre-warm buffers to reduce precipitation and add compound last with vigorous mixing.
• Polarity class: PROTACs often span polar and lipophilic domains; amphiphilic behavior and aggregation are possible. Assess with light scattering or solubility screens.
• Formulation aids (general): Small amounts of nonionic surfactants (e.g., 0.01–0.05% Tween-20 or Pluronic F-68) or serum proteins can improve apparent solubility; verify that such additives do not perturb your assay.

Comparison notes (general):

• DMSO vs DMF: DMSO is typically preferred for bioassays; DMF can increase solubility but may be less tolerated by cells.
• Add acid/base: Adjusting pH rarely helps if ionizable groups are limited; use with caution to avoid compound degradation.

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

Storage and Reconstitution

Item-specific information from Product Data:

• Storage Conditions: Store at −20°C.
• Shipping: Ice chest with ice pads.

Additional general guidance (not item-specific requirements):

• Upon receipt: Allow the sealed container to equilibrate to room temperature in a desiccated environment before opening to minimize moisture condensation on cold solids.
• Reconstitution: If supplied as a solid and structure permits, prepare a concentrated DMSO stock (e.g., 10–50 mM) to minimize freeze–thaw cycles. If solution is supplied, verify solvent and concentration on the label/CoA.
• Aliquoting: Dispense single-use aliquots in low-bind tubes; purge headspace with inert gas if the compound is air/moisture sensitive (item-specific sensitivity not provided).
• Storage of solutions: Store aliquots at −20°C or lower, protected from light. Avoid repeated freeze–thaw; thaw quickly at room temperature and refreeze promptly.
• Stability: Item-specific shelf life and solution stability are not specified; refer to CoA/Spec Sheet and confirm by LC–MS/HPLC over time as needed.

Always follow the SDS for handling and disposal. For any uncertainties about solvent compatibility or long-term stability, consult the lot-specific CoA/Spec Sheet before use.

Structure and Identity

Brief description: PROTAC AKR1C3 degrader-1 is a heterobifunctional small molecule designed for targeted protein degradation of AKR1C3 via the ubiquitin–proteasome system.

• SKU: P1438688
• Product Name: PROTAC AKR1C3 degrader-1
• Category: Small molecules and compound libraries (研究用途)
• CAS: P1438688 (internal catalog identifier)
• 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 PROTAC architecture; literature context, not item-specific):

• A typical PROTAC contains: (a) a target ligand that binds AKR1C3, (b) a linker (alkyl, PEG, or mixed motifs), and (c) an E3 ligase ligand (often CRBN- or VHL-based in literature). The precise motifs for this item are not specified.
• Stereochemistry: Many PROTACs contain multiple stereocenters due to chiral E3 ligase ligands and/or target binders; stereochemical configuration for this item is not specified.
• 2D description (general): Two pharmacophores connected by a flexible linker, featuring multiple heteroatoms (O/N) enabling hydrogen bonding; polar surface area is typically high for PROTACs. The exact arrangement for this item is not specified.

Identity notes:

• This entry is supplied as a research compound for AKR1C3 degradation studies. Definitive identification parameters (exact MF, MW, spectral data) should be taken from the item’s CoA/SDS.

Synthetic Utility

As supplied, PROTAC AKR1C3 degrader-1 is an end-use chemical biology probe rather than a synthetic building block. Its utility lies in biological interrogation rather than in serving as a reagent or substrate in chemical reactions.

General synthetic context of PROTACs (literature, not item-specific):

• Modular assembly: Typical synthetic routes couple a target-binding warhead and an E3 ligase ligand via a linker using amide couplings, click chemistry (CuAAC), carbonate/urethane formation, or SNAr/alkylation depending on anchor points.
• Linker engineering: PEG, alkyl, and heteroatom-containing linkers modulate physicochemical properties and ternary complex formation; late-stage diversification is common to explore SAR.
• Protecting-group strategy: Orthogonal protection may be needed to independently elaborate each pharmacophore and install the linker.
• Purification/analysis: Preparative HPLC is often required due to polarity and high MW; HRMS and multidimensional NMR are used for characterization.

Using this product synthetically:

• Not typically recommended; no reactivity or coupling handles are specified in the product data. If derivatization is desired, obtain structural information from the CoA/Spec Sheet and confirm compatibility experimentally.

Conclusion: Treat this item as a finished probe unless explicit structural handles and reactivity are disclosed in the provided documentation.

Target Specificity

Only product-data-sourced details may be listed here.

• Intended target class: AKR1C3 (aldo-keto reductase 1C3) based on the product name.
• Target specificity metrics (e.g., DC50, Dmax, off-target panel, E3 ligase used): Not specified for this item; refer to CoA/Spec Sheet.
• Species cross-reactivity: Not specified for this item; refer to CoA/Spec Sheet.
• Epitope/binding site: Not applicable; small-molecule degrader.

Notes:

• In the absence of item-specific validation data, users should perform their own target engagement and degradation verification using appropriate controls.
• If the supplier provides supplemental documents (CoA, technical data sheet), consult them for any available potency and selectivity information.

Häufig gestellte Fragen

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 P1438688, the molecular formula is C45H43N7O10, and the molecular weight is 841.86 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.