ER degrader 9 , CAS No.3023359-75-0

CAS: 3023359-75-0 Cat. No.: E1449837 Fórmula: C₄₀H₄₈N₄O₂ Peso molecular: 616.83

Storage

Store at -20°C

Shipped In

Ice chest + Ice pads

Visão geral

ER degrader 9 (compound 1), a bifunctional molecular glue , is a potent estrogen receptor (ER) degrader with a DC 50 of ≤10 nM in MCF-7 cells. ER degrader 9 can be used for the research of breast cancer.

Specifications

Condições de armazenamento de armazenamento

Store at -20°C

Enviado em

Ice chest + Ice pads

Este produto requer transporte de cadeia fria. Serviços terrestres e outros serviços econômicos não estão disponíveis.

Tipo de ação

INHIBITOR

Nomes e identificadores

Peso molecular

616.83

Application Protocols

Item-specific facts (from Product Data)

• No tested applications or recommended dilutions are provided for this item.

General example protocols (literature; not item-specific)

1. Cell-based ER degradation assay (example)

• Prepare a 10 mM DMSO stock; serially dilute to 10-point dose range (e.g., 0.1 nM–10 µM) maintaining constant DMSO (≤0.1% v/v final).
• Seed ER+ cells (e.g., MCF-7 or T47D) in phenol-red–free medium with charcoal-stripped serum. Treat for 4–24 h.
• Lyse cells; quantify ERα by Western blot or ELISA. Fit DC50 and Dmax from normalized band intensities.
• Controls: DMSO vehicle, known SERD, proteasome inhibitor rescue, and inactive analog.

2. ER transcriptional reporter assay (example)

• Transfect cells with ERE-luciferase reporter or use a stable line. Treat with estradiol ± degrader for 16–24 h.
• Measure luciferase; calculate percent inhibition of E2-stimulated signal vs vehicle.

3. Ternary complex assessment (example)

• Use NanoBRET or TR-FRET with labeled ER and E3 ligase proteins in the presence of degrader. Determine cooperativity and apparent KD values.

Notes

• Verify compound solubility at working concentrations and absence of precipitation after dilution. These protocols are general templates and must be optimized for ER degrader 9. No performance claims are made for this specific item.

Biological Roles

Scope note

• The following summarizes estrogen receptor (ER) biology in general and the research rationale for using ER degraders. It is not specific to ER degrader 9, for which detailed activity data are not provided.

Estrogen receptor biology (general)

• ERα (ESR1) and ERβ (ESR2) are ligand-activated nuclear receptors that regulate transcription by binding estrogen response elements (EREs) and recruiting coactivators/corepressors. ERα is predominant in reproductive tissues, breast, liver, and bone; ERβ has broader but often lower expression.
• ER signaling controls cell proliferation, differentiation, metabolism, and homeostasis. Crosstalk occurs with MAPK/PI3K pathways and growth factor signaling.
• Post-translational regulation includes phosphorylation, acetylation, and ubiquitination; receptor turnover is proteasome-dependent and ligand-modulated.

Rationale for degraders (general)

• Degraders enable event-driven pharmacology: transient ternary complex formation can drive sustained receptor depletion, offering sharper on/off control than occupancy-based antagonists. They can overcome certain resistance mechanisms associated with point mutations or altered cofactor dependencies by removing the target protein rather than blocking it.
• Research applications include elucidating ER-dependent gene networks, studying chromatin binding dynamics (ChIP-seq/PRO-seq), and dissecting non-genomic ER functions.

Selectivity considerations (general)

• Isoform selectivity (ERα vs ERβ) and proteome-wide off-target degradation depend on warhead selectivity, linker geometry, and E3 ligase choice. Orthogonal assays (proteomics, CETSA, imaging) are recommended to confirm on-target activity for any specific degrader.

Buffer Applications

Relevance

• ER degrader 9 is a small-molecule research tool and is not itself a buffering agent. Therefore, classical buffer recipes (e.g., phosphate, Tris, HEPES) do not apply to this compound directly.

Assay buffer considerations (general; not item-specific)

• For biochemical binding or cell-based assays, prepare working solutions by diluting a DMSO stock into an appropriate buffer or medium immediately before use.
  • Biochemical assays: Use 1× assay buffer (e.g., 25–50 mM HEPES or Tris, 100–150 mM NaCl, 0.01–0.05% Tween 20, 1–2 mM DTT if redox stability is required). Maintain constant DMSO across all wells.
  • Cell culture: Use complete medium (e.g., phenol-red–free DMEM/RPMI with charcoal-stripped serum for estrogen-response studies) to minimize background ER activation. Keep final DMSO ≤0.1–0.5% v/v.
• Adsorption/precipitation: To reduce compound loss, pre-wet plasticware with buffer containing the same DMSO percentage as the final solution and mix gently to avoid precipitation.

Quality control in buffers

• Confirm compound concentration after dilution (e.g., by UV–vis if chromophore is known, or LC–MS for definitive quantitation). Verify that the degrader remains in solution and that pH/ionic strength do not compromise stability.

Note

• No item-specific buffer compatibility data are available for ER degrader 9; verify empirically for your assay.

Green Alternatives

Context

• This product is a specialized research chemical used at micromolar or lower concentrations. “Green alternatives” relate primarily to handling solvents and experimental design rather than replacing the active degrader scaffold.

Greener handling strategies (general; not item-specific)

• Prefer aqueous-compatible delivery: Minimize DMSO percentage in assays (≤0.1–0.2% v/v when feasible) to reduce solvent burden.
• Solvent choice for stock preparation: DMSO is generally safer than DMF or NMP from a regulatory and exposure standpoint. Avoid chlorinated solvents in routine biological workflows.
• Waste minimization: Plan dose–response plates to avoid excess solution. Use intermediate working stocks to reduce dead volume. Collect DMSO-containing waste separately for appropriate disposal.
• Energy use: Store only necessary aliquots at −20°C; avoid repeated door openings and prolonged bench time. Shipments are already optimized (ice chest + ice pads per Product Data).

Comparison of common solvents (general)

• DMSO vs DMF/NMP: DMSO has a more favorable environmental and occupational profile and is widely accepted for biological assays; DMF/NMP are reproductive toxins (consult SDS) and should be avoided where possible.
• EtOH as co-solvent: While “greener,” ethanol often fails to dissolve high-MW degraders and can perturb cells at low percentages. Use judiciously.

Alternative modalities

• If degradation is the goal but solubility is limiting, consider lipid-based delivery or cyclodextrin inclusion complexes to reduce organic solvent content (validate for system compatibility).

Pharmaceutical Uses

Item-specific facts (from Product Data)

• None provided. This product is designated for research use only.

General context (not item-specific)

• Heterobifunctional degraders are under investigation as discovery tools and early-stage leads in medicinal chemistry. In a pharmaceutical R&D setting, reference degraders may be employed to validate targets, benchmark SERD/SERM programs, or explore degrader pharmacology in preclinical systems.
• Formulation considerations for discovery studies include solubilization (DMSO concentrates, cosolvent systems, or nanosuspensions), stability (hydrolysis of linker functionalities), and adsorption to plastics.
• Regulatory status: Research-use-only reagents like this are not manufactured under GMP and are not suitable as drug substances or excipients. No pharmacopeial monograph applies.

Applications in development workflows (general)

• As positive controls in biochemical or cellular degradation assays to qualify assay performance.
• As internal standards or tool compounds in ADME method development (e.g., microsomal stability, plasma protein binding) to understand class behavior.

Notes

• No claims are made regarding therapeutic use, safety, or efficacy. Any use beyond research, including diagnostic or clinical applications, is not covered by this listing and would require appropriate regulatory qualification and validation.

Physical Properties

Item-specific facts (from Product Data)

• Physical form/appearance: Not specified for this item; refer to CoA/Spec Sheet.
• Melting point, boiling point, 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/literature expectations for ER-targeting PROTAC-like degraders (not item-specific)

• Aggregate physicochemical profile: high molecular weight and polarity relative to traditional small-molecule inhibitors; often MW ~700–1200 Da; topological polar surface area frequently >130 Ų; cLogP typically 2–5; multiple HBD/HBA sites. These are descriptive ranges observed in literature for PROTAC chemotypes and are not specifications for ER degrader 9.
• Physical state: frequently isolated as amorphous solids or foams; may be hygroscopic depending on linker composition.
• Solubility behavior: commonly soluble at assay-relevant concentrations in DMSO; may require co-solvent systems (DMSO + aqueous buffer with surfactant or cyclodextrin) for cell-based delivery. Limited aqueous solubility at neutral pH is typical.
• Stability considerations: amide/ester/carbamate linkers may show hydrolytic lability in strongly acidic or basic media and at elevated temperature. Protect from prolonged light and moisture when possible.

Practical notes

• For solution preparation, start with DMSO stocks (e.g., 10 mM) and dilute into assay buffer while keeping final DMSO ≤0.1–0.5% (v/v) as tolerated by the biological system (literature guidance). Verify actual solubility and stability experimentally for ER degrader 9.

Quality and Grades

Item-specific facts (from Product Data)

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

Context and expectations (general; not item-specific)

• Small-molecule library/chemical probe materials are typically offered at high purity suitable for biochemical and cellular research (often ≥95% by HPLC), low residual solvents/metals, and accompanied by identity confirmation (e.g., HRMS/1H NMR). For ER degrader 9, the exact acceptance criteria are not stated here; consult the CoA.
• If a stabilizer is present, it will be listed on the CoA/Spec. No stabilizer is specified for this product listing.
• Analytical data packages: Common characterization includes HPLC chromatograms, MS, and sometimes NMR. UV cutoff and trace impurity limits are not specified for this item.

How to interpret grades (general guidance)

• “Screening” or “research” grade: Emphasizes purity adequate for in vitro and cell-based assays, but not qualified for clinical or GMP use.
• If “HPLC grade” is mentioned for solvents (not applicable here), it denotes low UV background. For solids like degraders, reported purity typically refers to area % by HPLC/UPLC at a defined wavelength and method.

Recommendations

• Verify purity and identity against your assay’s sensitivity. For quantitative applications (e.g., Kd/EC50 determination), consider running an in-house orthogonal check (qNMR or LC–HRMS) in addition to the supplied CoA.

Reaction and Applications

Item-specific facts (from Product Data)

• Manufacturer applications: Not specified beyond the product name “ER degrader 9.”

General applications for ER-targeting degraders (literature; not item-specific)

• Mechanism: Heterobifunctional degraders bring ER into proximity with an E3 ubiquitin ligase, promoting ubiquitination and subsequent proteasomal degradation. This contrasts with occupancy-based antagonists that merely block the receptor.
• Use cases in research: Time-resolved knockdown of ER signaling in ER-expressing cells; probing ERα vs ERβ functional roles; studying receptor resynthesis kinetics; benchmarking against SERDs/SERMs and tool degraders.
• Assay modalities: Western blot quantification of ER levels (DC50/Dmax), qPCR of ER target genes, reporter assays for ERE-driven transcription, and cell viability/proliferation phenotypes in ER+ lines.
• Controls: Include inactive analogs, the individual warheads, proteasome inhibitor rescue (e.g., MG132) to confirm proteasome dependence, and washout studies to assess recovery.
• Practical tips: Maintain consistent DMSO across wells; use fresh dilutions; verify absence of precipitation after dilution. Pre-treat cells 2–24 h depending on degradation kinetics; extend to 48–72 h for phenotypic readouts, refreshing compound if needed.
• Orthogonal validation: Use proteomics (TMT/label-free) to assess off-target degradation; perform ternary complex assays (TR-FRET, NanoBRET, SPR) to characterize cooperative binding.

Note

• The specific E3 ligase moiety, binding affinity, and degradation profile for ER degrader 9 are not provided here; consult primary data if available.

Reaction Conditions

Applicability note

• This section provides general, literature-based conditions commonly used in assembling heterobifunctional degraders. It is not specific to ER degrader 9, for which no synthetic details are provided.

Typical bond-forming steps (general; not item-specific)

• Amide couplings: HATU (1.1–1.5 eq) or EDC·HCl/HOBt or Oxyma/DIPEA in DMF or NMP, 0 °C to rt, 1–12 h. For sterically hindered partners, use HOAt derivatives or T3P in EtOAc/DMF. Monitor by LC–MS.
• Carbamate formation: CDI or triphosgene with alcohol/amine partners; or p-nitrophenyl chloroformate activation, 0 °C to rt. Avoid moisture; quench carefully.
• Urea linkage: CDI or 1,1′-carbonyldiimidazole-mediated coupling of amines; alternatively, isocyanate routes under dry conditions.
• Click chemistry (CuAAC): CuSO4/sodium ascorbate or preformed Cu(I) catalysts in t-BuOH/H2O or DMF/H2O (rt–40 °C, 1–6 h). Use copper-scavenging resins during workup.
• Reductive amination: NaBH3CN or NaBH(OAc)3 in DCE/MeOH or DMF, rt–40 °C, 2–16 h; protect other electrophiles.

Workup and purification

• Reverse-phase prep HPLC with water/MeCN or water/MeOH (0.05–0.1% formic acid or ammonium bicarbonate buffer) is standard. Lyophilization affords TFA or acetate salts depending on mobile phase; counterion exchange may be needed.

Stability cautions

• Avoid prolonged exposure to strong base/acids that can cleave esters/carbamates. Sensitive motifs (e.g., thalidomide-like imides) may epimerize or hydrolyze; keep temperatures moderate and exclude moisture.

Safety and Handling

Item-specific facts (from Product Data)

• GHS classification, signal word, H-statements, pictograms: Not specified for this item; refer to SDS.
• Storage conditions: Store at -20°C (per Product Data).

General safety guidance for small-molecule degraders (not item-specific)

• Intended use: For research use only. Not for human or veterinary use.
• PPE: Wear lab coat, safety glasses, and appropriate chemical-resistant gloves. Handle powders and DMSO solutions in a fume hood to avoid inhalation and dermal exposure.
• Incompatibilities: Avoid strong acids/bases and strong oxidizers unless compatibility is known. Protect from moisture; many linker-bearing molecules hydrolyze under harsh conditions.
• Hygroscopicity: Some degraders can be hygroscopic; keep containers tightly closed with desiccant as needed.
• First aid (overview; defer to SDS): Inhalation—move to fresh air; Skin—wash with soap and water; Eyes—rinse cautiously with water for several minutes; Ingestion—rinse mouth, seek medical attention.
• Spill/cleanup: Avoid dust formation. Absorb small liquid spills with inert material; collect solids by gentle sweeping with minimal dusting; dispose of according to institutional chemical waste procedures.
• Stability and handling: Minimize freeze–thaw cycles; aliquot solutions. Filter sterilize solutions for cell-based work if appropriate.

Notes

• Because hazard statements are not provided for this specific item, consult the product SDS for authoritative hazard, toxicological, and regulatory information prior to use.

Solvent Selection

Item-specific facts (from Product Data)

• No item-specific solubility or solvent recommendations are provided.

General solvent guidance for ER-targeting degraders (literature; not item-specific)

• Primary solvent: DMSO is the standard for preparing concentrated stock solutions (e.g., 5–20 mM), owing to high solvating power for polar, high-MW molecules.
• Aqueous delivery: Dilute DMSO stocks into buffered saline or culture media immediately prior to use. Aim for a final DMSO content compatible with the system (commonly ≤0.1–0.5% v/v for sensitive cells).
• Co-solvent strategies: If precipitation occurs on dilution, consider:
  • DMSO + PEG400 (1–5%) or ethanol (≤0.1%) before adding buffer
  • Cyclodextrin complexation (e.g., HP-β-CD 2–10% w/v) for enhanced apparent solubility
  • Surfactants at low levels (e.g., 0.01–0.05% Tween 80) for biochemical assays (validate for target compatibility)
• pH effects: Most degraders lack strong ionizable groups; adjusting pH often offers limited solubility gains and may compromise stability of amide/carbamate linkers.
• Filtration: Use low-protein-binding 0.22 µm filters for assay solutions to remove particulates.

Comparison (general)

• DMSO vs DMF: DMSO preferred for bioassays due to lower volatility and better biocompatibility at low %; DMF is an alternative for stock preparation but is less favored for biological dilution.
• DMSO vs neat ethanol: Ethanol is often less effective for highly polar, high-MW degraders and is typically limited to trace levels in biological systems.

Storage and Reconstitution

Item-specific facts (from Product Data)

• Storage conditions: Store at -20°C.
• Shipping: Ice chest + ice pads.

General guidance (not item-specific)

• Container: Keep tightly closed under inert atmosphere or with desiccant to limit moisture uptake. Protect from light when possible.
• Solid handling: Allow vial to equilibrate to room temperature in a desiccator before opening to minimize condensation. Reseal promptly.
• Reconstitution: Prepare concentrated stocks in anhydrous DMSO (e.g., 5–20 mM). If sterile solutions are required for cell assays, pass through a 0.22 µm low-binding filter into sterile tubes.
• Aliquoting: Dispense single-use aliquots to avoid repeated freeze–thaw. Store aliquots at -20°C or below. Record preparation date and concentration on labels.
• Stability: Long-term stability, water content limits, and peroxide/metal specifications are not provided for this item; refer to the CoA/Spec Sheet. Reassess potency periodically by LC–MS or a functional assay if stored for extended periods.
• Thawing/usage: Thaw aliquots on ice, vortex gently to ensure homogeneity, and avoid repeated temperature cycling. Discard aliquots showing visible precipitation or color change unless resolubilization and identity are verified.

Note

• For research use only. Always consult the SDS for detailed safety instructions before handling or preparing solutions.

Structure and Identity

Item-specific facts (from Product Data)

• SKU: E1449837
• Product Name: ER degrader 9
• CAS: 3023359-75-0
• Molecular formula: Not specified for this item; refer to CoA/Spec Sheet.
• Molecular weight: Not specified for this item; refer to CoA/Spec Sheet.
• InChIKey: Not specified for this item; refer to CoA/Spec Sheet.
• SMILES: Not specified for this item; refer to CoA/Spec Sheet.

General/literature description (not item-specific)

• Structural class: Heterobifunctional small molecule (PROTAC-style) designed to induce proteasomal degradation of the estrogen receptor (ER). Such degraders typically comprise: (1) an ER-binding warhead (often derived from high-affinity ER ligands), (2) a linker (alkyl, PEG, or mixed), and (3) an E3 ligase-recruiting moiety (e.g., CRBN- or VHL-binding headgroup). The exact components for ER degrader 9 are not provided here.
• Functional groups commonly encountered in ER degraders (literature): amides/ureas/carbamates for linker attachment; heteroaromatics in the ER ligand; tertiary alcohols or nitriles in E3 ligase binders; multiple heteroatoms enabling hydrogen bonding.
• 2D structural features (typical for ER-targeting degraders, literature): two pharmacophore-rich termini connected by a flexible or semi-rigid linker. One terminus complements the ER ligand-binding domain; the other presents the E3-ligase binder. Multiple rotatable bonds and high polarity compared with classical inhibitors.

Notes

• Because no structure identifiers are provided for this catalog item, all structural specifics above are general to ER-targeted degraders and should not be interpreted as the exact structure of ER degrader 9.

Synthetic Utility

Relevance

• ER degrader 9 is a finished research tool compound rather than a building block. Nevertheless, knowledge of typical synthetic strategies for ER-targeted degraders can inform analog design and troubleshooting.

General synthetic features of ER degraders (literature; not item-specific)

• Modular assembly: Three components—ER-binding warhead, linker, and E3 ligase binder—are assembled via robust chemistries such as amide coupling, carbamate formation, urea linkage, or click reactions. Protecting group strategies (Boc, Fmoc, TBDMS) are used to control chemoselectivity.
• Linker installation: PEG or alkyl linkers are introduced as diols/diamines/dicarboxylates. Orthogonal handles (e.g., azide/alkyne for CuAAC) facilitate convergent routes.
• Warhead and ligase binder derivatization: Installation at positions that retain high binding affinity is critical; SAR often explores linker length (n = 2–8), composition (PEG vs alkyl), and exit vectors.
• Purification: Due to polarity and MW, reverse-phase preparative HPLC is commonly required. Ion-pairing is avoided if possible to simplify desalting.

Analytical characterization (general)

• LC–MS for mass confirmation; 1H/13C NMR for structural verification (sometimes broadened signals due to conformational heterogeneity); HRMS for exact mass; UPLC purity at multiple wavelengths.

Note

• No synthetic route, intermediates, or reagents are provided for ER degrader 9; the above is general background and not a specification or route for this specific item.

Target Specificity

Item-specific facts (from Product Data)

• Target, isoform selectivity, and E3 ligase recruitment specifics: Not specified for this item; refer to technical data if available.

General/literature context (not item-specific)

• ER degraders are designed to reduce levels of estrogen receptor proteins in cells, most often ERα. Selectivity across ERα vs ERβ depends on the ER-binding warhead and linker exit vector.
• Off-target profile: Proteome-wide selectivity is highly dependent on the ternary complex geometry and the E3 ligase recruiter used (e.g., CRBN vs VHL). Unintended degradation of neosubstrates is a known risk; global proteomics is recommended in new systems.
• Cellular context: Degradation efficacy can vary by cell line due to expression of E3 ligase machinery, ER co-regulators, and proteasome capacity. Time- and dose-dependence are typical, with potential hook effects at high concentrations.

Recommendation

• For ER degrader 9, determine specificity empirically with: concentration-dependent degradation curves (DC50/Dmax), washout recovery, proteasome dependency (rescue with MG132), and selectivity against ERβ and unrelated nuclear receptors as negative controls.