Raloxifene HCl - 10mM in DMSO , Estrogen receptor beta modulator, CAS No.82640-04-8, Estrogen receptor beta modulator

CAS: 82640-04-8 Cat. No.: R408663 Summenformel: C₂₈H₂₇NO₄S·HCl Molekulargewicht: 510.04 EG-Nummer: 639-789-7 PubChem CID: 54900

GRADE & PURITY 10mM in DMSO

Synonyms

LY156758 (Keoxifene) HCl | [6-​hydroxy-​2-​(4-​hydroxyphenyl)​benzo[b]​thien-​3-​yl]​[4-​[2-​(1-​piperidinyl)​ethoxy]​phenyl]​-​methanone,hydrochloride (1:1)

Storage

Store at -80°C

Shipped In

Dry ice packs + Cold packs

Übersicht

Information

Raloxifene (LY156758, Keoxifene) HCl a selective and orally activeestrogen receptormodulator (SERM), which inhibits human cytosolic aldehyde oxidase-catalyzed phthalazine oxidation activity withIC50of 5.7 nM.
In vitro

Raloxifene, has been demonstrated as a potent uncompetitive inhibitor of human liver aldehyde oxidase-catalyzed oxidation of phthalazine, vanillin, and nicotine-Delta1\'(5\')-iminium ion, with Ki values of 0.87 nM, 1.2 nM and 1.4 nM. Raloxifene has also been shown to be a noncompetitive inhibitor of an aldehyde oxidase-catalyzed reduction reaction of a hydroxamic acid-containing compound, with a Ki of 51 nM. Raloxifene activates TGF beta 3 promoter as a full agonist at nanomolar concentrations, and raloxifene inhibits the estrogen response element-containing vitellogenin promoter expression as a pure estrogen antagonist in transient transfection assays.

In vivo

Raloxifene restores both bone mineral density and TGF beta 3 messenger RNA expression in the femur to levels measured in intact rats. Raloxifene (0.1 mg/kg-10 mg/kg, orally for 5 weeks) increases bone mineral density in the distal femur and proximal tibia in ovariectomized (OVX) rat. Raloxifene reduces serum cholesteroloral with ED50 of 0.2 mg/kg in ovariectomized (OVX) rat. Raloxifene diverges dramatically from estrogen in its lack of significant estrogenic effects on uterine tissue. Raloxifene prevents cancellous osteopenia as well as the changes in radial bone growth, bone resorption, and blood cholesterol, but is less effective in reducing cancellous bone formation and does not prevent uterine atrophy in ovariectomized (OVX) rats. Raloxifene (3 mg/kg/day) has potent estrogenic activity on bone resorption and serum cholesterol, a lesser effect on bone formation, and minimal activity on uterine wet weight in ovariectomized (OVX) rats.
Cell Data

cell lines：182 solid and hematologic tumor cell lines

Concentrations：

Incubation Time：

Powder Purity:≥99%

Specifications

Synonyme

LY156758 (Keoxifene) HCl | [6-​hydroxy-​2-​(4-​hydroxyphenyl)​benzo[b]​thien-​3-​yl]​[4-​[2-​(1-​piperidinyl)​ethoxy]​phenyl]​-​methanone,hydrochloride (1:1)

Spezifikationen & Reinheit

10mM in DMSO

Biochemische und physiologische Mechanismen

Raloxifene (LY156758, Keoxifene) HCl a selective and orally active estrogen receptor modulator (SERM), which inhibits human cytosolic aldehyde oxidase-catalyzed phthalazine oxidation activity with IC50 of 5.7 nM.

Storage

Store at -80°C

Verschickt in

Dry ice packs + Cold packs

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

Aktionsart

MODULATOR

Mechanismus der Wirkung

Estrogen receptor beta modulator

Namen und Kennungen

Isomere SMILES

C1CCN(CC1)CCOC2=CC=C(C=C2)C(=O)C3=C(SC4=C3C=CC(=C4)O)C5=CC=C(C=C5)O.Cl

WGK Deutschland

3

PubChem CID

54900

Molekulargewicht

510.04

Chemische und physikalische Eigenschaften

• Löslichkeit: Solubility (25°C) In vitro

Application Protocols

No antibody-type or kit-style application protocols are defined for this small molecule in the Product Data.

• Typical research handling (general):
  • Prepare a concentrated DMSO stock (e.g., 10 mM). Vortex and, if needed, sonicate briefly to dissolve fully.
  • Dilute into pre-warmed assay buffer or media with vigorous mixing to minimize precipitation; keep final DMSO content compatible with the biological system (≤0.1–0.5% v/v as permitted).
  • Include vehicle controls (matching DMSO %) and, where relevant, positive/negative control ligands.
  • Filter sterilize (0.22 µm PTFE) if sterile solutions are required for cell-based assays; assess compound stability under assay conditions (light, pH, time).

These are general laboratory practices and not item-specific validated protocols.

Biological Roles

This section provides literature-based context only and does not imply any approved use. Raloxifene is widely known as a selective estrogen receptor modulator (SERM); the hydrochloride salt is commonly used as a reference reagent in receptor biology.

• Molecular targets (literature): binds estrogen receptors ERα and ERβ with tissue-selective agonist/antagonist activity; interactions are mediated by the triphenylethylene-like scaffold and phenolic H-bond donors.
• Mechanistic features (literature): ligand binding alters ER conformation and co-regulator recruitment; phenolic groups engage the ER ligand-binding domain via hydrogen bonding; tertiary amine can influence ionic interactions and pKa-dependent partitioning.
• In vitro usage (typical research practice): employed as a tool compound in receptor-binding assays, reporter gene systems, and in studies of ER-dependent transcriptional modulation; also explored in studies of osteogenic signaling and lipid metabolism pathways in cellular models.
• ADME-relevant properties (literature, general): high plasma protein binding; undergoes phase II conjugation (glucuronidation) at phenols; metabolism and transport are complex and species-dependent.

Important: All statements here are for biochemical research context only. This catalog item is for research use only and not for diagnostic or therapeutic applications.

Buffer Applications

Raloxifene HCl is not a buffering reagent. It does not define a useful conjugate acid/base pair for maintaining solution pH in typical biochemical buffers.

• Practical note: When preparing aqueous working solutions for assays, use established buffers (e.g., PBS, HEPES, or acetate) and dissolve raloxifene HCl first in a small volume of DMSO, then dilute into the buffer with vigorous mixing to prevent precipitation. Slightly acidic buffers (e.g., acetate pH 4.5–5.5) can improve apparent solubility for the HCl salt.

Green Alternatives

This product is a solid research compound, not a process solvent. Green chemistry considerations primarily involve the choice of dissolution and reaction media, purification, and waste minimization when working with phenolic, lipophilic amines.

• Solvent selection (literature, comparison):

  • DMSO vs DMF/NMP: DMSO is generally preferred from a hazard profile standpoint (non-reprotoxic, lower regulatory concern) but has odor and high boiling point; DMF and NMP are reproductive toxins and should be minimized.
  • Ethyl acetate and 2-MeTHF can sometimes replace dichloromethane for workups or normal-phase chromatography, though compound polarity may necessitate some MeOH modifier.
  • For reverse-phase prep HPLC, ethanol or isopropanol can partially replace acetonitrile in gradients to reduce solvent impact, subject to solubility and resolution.

• Small comparison table (general guidance):

  • DMF/NMP: excellent solubilizers; high regulatory concern; consider DMSO or propylene carbonate as alternatives when feasible.
  • Dichloromethane: effective eluent; high environmental impact; consider EtOAc or 2-MeTHF where resolution allows.
  • Acetonitrile: good for RP-HPLC; solvent-intensive; partial substitution with ethanol may be possible with method revalidation.

• Operational green tips:

  • Use concentrated DMSO stocks and aqueous dilution to reduce organic solvent volumes.
  • Employ miniaturized assays and micro-scale derivatization to decrease waste.
  • Capture and segregate halogenated versus non-halogenated waste for optimized disposal.

Pharmaceutical Uses

This information pertains to formulation science context only and does not constitute any medical claim.

• Excipient/monograph status: Item-specific pharmacopeial compliance is Not specified for this item; refer to CoA/Spec Sheet. Raloxifene hydrochloride appears in pharmacopeial monographs for quality control in pharmaceutical manufacturing, but this listing does not assert such compliance.
• Formulation considerations (literature):
  • Salt selection: the hydrochloride salt improves stability and aqueous compatibility relative to the free base; counterion content must be accounted for in dosing and assay calculations.
  • Solid-state behavior: multiple polymorphs/solvates have been reported in the literature; hydrate/solvate state can impact dissolution rate and processing.
  • Solubilization: solid dispersions, cyclodextrin inclusion, or micellar systems have been explored to enhance apparent solubility for in vitro studies.
• Manufacturing context: in a GMP environment, control of residual solvents, particle size distribution, and polymorph is critical; none of these attributes are specified for this research-grade listing.

Physical Properties

Only general/literature information is provided here; these are not item-specific specifications.

• Appearance (item-specific): Not specified for this item; refer to CoA/Spec Sheet.
• Grade/Purity (item-specific): Not specified for this item; refer to CoA/Spec Sheet.
• Molecular weight (literature): ~510.05 g/mol (hydrochloride salt, C28H28ClNO4S).
• Physical state (literature): organic solid (salt); typically obtained as a crystalline powder.
• Melting behavior (literature): high melting solid; reported decomposition occurs >200 °C (exact MP range depends on form/hydration; consult primary references).
• Solubility (literature, qualitative):
  • Water: the HCl salt improves aqueous solubility versus free base; sparingly to moderately soluble in neutral water; higher solubility in acidic aqueous media due to ammonium formation.
  • Organic: soluble in polar aprotic solvents (e.g., DMSO, DMF); limited solubility in lower alcohols; very low in nonpolar solvents (hexanes, toluene).
• Partitioning (literature): high intrinsic lipophilicity for the free base (logP >4); effective logD of the HCl salt is lower and pH-dependent.
• pKa (literature): tertiary amine pKa (conjugate acid) typically in the ~8–9 range; phenolic pKa values in the ~9–10 range; ionization and solubility are strongly pH-dependent.
• UV/Vis (literature): aromatic chromophores with strong UV absorption in the 200–300 nm region; specific cutoffs/epsilon not established here.

Note: For exact numerical specifications (mp, water content, UV cutoff, metal content, etc.) of this catalog item, see the CoA/Spec Sheet.

Quality and Grades

• Item-specific grade/purity: Not specified for this item; refer to CoA/Spec Sheet.
• What grade means (general guidance):
  • Research/biochemical grade typically implies suitability for in vitro/biochemical assays with low levels of common synthetic impurities. HPLC or LC–MS chromatograms often accompany such listings to document purity and identity.
  • Pharmaceutical/USP/EP grades (if applicable) specify monograph-defined tests (ID, assay, impurities, residual solvents). This listing does not state pharmacopeial compliance.
• Identity confirmation (typical tools): 1H/13C NMR, LC–MS/HRMS, HPLC purity, melting behavior, and in some cases water content (KF). For salts, chloride content or titration may be used to confirm salt stoichiometry.
• Stabilizers: None indicated for this item. If stabilizers are present in a lot, they would be disclosed on the CoA.
• Practical advice:
  • If using for quantitative biology/assays, verify purity and counterion content from the CoA to calculate accurate molar concentrations (use MW of the HCl salt as specified on the lot’s CoA).
  • If UV detection is used, check the CoA for UV absorbance baseline suitability and potential interfering impurities.

Reaction and Applications

As a phenolic, benzothiophene-containing tertiary amine salt, raloxifene HCl is mainly used as a reference standard, tool compound, or library member in medicinal chemistry and chemical biology. From a synthetic chemistry perspective, the scaffold presents several handles for late-stage modification.

• Research applications (manufacturer category context): part of a small-molecule/compound library for screening, SAR, and receptor-binding studies in vitro (no medical/clinical use).
• Functional group reactivity (literature):
  • Phenolic OH groups: amenable to selective protection (e.g., silyl/benzyl ethers) or activation (e.g., carbonate formation) for subsequent cross-couplings or etherifications.
  • Tertiary amine (as HCl salt): liberate free base for acylation/alkylation or for salt metathesis to alternative counterions; quaternization possible but impacts receptor binding.
  • Aryl C–O bonds: under Pd catalysis, aryl aryl-ether cleavage is challenging; more common are O-alkylations forming aryl alkyl ethers.
  • Benzothiophene ring: electrophilic aromatic substitution is possible on activated positions; metalation strategies require careful control due to phenols.
• Practical notes:
  • For derivatization, convert to the free base with a mild inorganic base (e.g., NaHCO3, aqueous workup) to enhance solubility in organic media, then re-form desired salt if needed.
  • Phenolic selectivity can be tuned using steric bulk and base choice (e.g., K2CO3 vs Cs2CO3) in polar aprotic solvents (DMF/DMSO) at 40–80 °C.
  • For analytical use (calibrants, controls), prepare solutions gravimetrically in DMSO and store aliquots at low temperature to minimize degradation.

Reaction Conditions

General, literature-based guidance for handling/derivatizing raloxifene-class compounds (not item-specific specs):

• O-Alkylation of phenols:
  • Typical: K2CO3 or Cs2CO3 (1.5–3.0 equiv) in DMF or acetone, 40–80 °C, 2–16 h; alkyl halide (1.2–2.0 equiv). Monitor for dialkylation; use steric/electronic control to bias mono- vs di-substitution.
• O-Acylation/carbamate formation:
  • Base: pyridine, DIPEA, or DMAP catalysis; acyl chloride or chloroformate (1.1–1.5 equiv) in DCM or THF, 0 °C to rt, 1–4 h.
• Salt metathesis (HCl → other acid):
  • Dissolve in minimal methanol/ethanol; add stoichiometric alternative acid (e.g., fumaric, mesylate, citrate) and evaporate or crystallize. Confirm stoichiometry by NMR/elemental analysis.
• Free base generation:
  • Partition between DCM and saturated NaHCO3/Na2CO3; isolate organic phase, dry, and concentrate. Avoid strong base that could induce phenolate-driven side reactions.
• Electrophilic aromatic substitution on benzothiophene (advanced):
  • Employ mild Lewis/Brønsted acids (e.g., FeCl3 or AcOH) at controlled temperature; protect phenols beforehand to maintain regioselectivity.
• Analytical/assay prep:
  • Stock solutions: 10–50 mM in DMSO; store aliquots at ≤ −20 °C; thaw on ice, avoid >3 freeze–thaw cycles.

Yields and exact conditions vary with substrate and substitution pattern; consult primary literature for the targeted transformation.

Safety and Handling

• Research use: For research use only. Not for human or veterinary use.
• GHS/SDS: Item-specific GHS classification, signal word, H-statements, and pictograms are Not specified for this item; refer to the product SDS for authoritative information.
• General hazards (literature/good lab practice):
  • May cause irritation to eyes, skin, and respiratory tract; harmful if swallowed. Avoid dust generation and inhalation.
  • Organic powder; handle to minimize airborne particulates. Use in a fume hood.
• PPE: laboratory coat, gloves (e.g., nitrile), and splash-resistant eye protection at minimum. Use a certified fume hood for weighing/handling.
• Incompatibilities (general): strong oxidizers may react with phenolic/aryl functionalities; strong bases/acids can alter ionization state and solubility; avoid prolonged exposure to moisture and light which may affect stability.
• First aid overview (general):
  • Inhalation: move to fresh air; seek medical attention if symptoms persist.
  • Skin: wash with soap and water; remove contaminated clothing.
  • Eyes: rinse cautiously with water for several minutes; remove contacts if present and easy; seek medical advice if irritation continues.
  • Ingestion: rinse mouth; do not induce vomiting; seek medical advice.
• Environmental: prevent release to the environment; collect spills with inert absorbent and dispose of as hazardous waste per institutional and local regulations.
• Storage note: See Storage & Reconstitution tab for item-specific storage; avoid repeated freeze–thaw of solutions.

Solvent Selection

This product is a solid small molecule, not a solvent. Selection of dissolution and reaction media is often critical for handling and for synthetic transformations involving raloxifene scaffolds.

• Polarity/miscibility considerations (literature):
  • Good solubility in polar aprotic solvents (DMSO, DMF, NMP). DMSO is typically preferred for biological stock solutions.
  • Limited solubility in water at neutral pH, improved in acidic buffers due to protonation of the amine (hydrochloride salt further assists aqueous compatibility).
  • Poor solubility in nonpolar solvents (hexanes) and limited in moderately polar protic solvents (ethanol, isopropanol) depending on temperature.
• Typical choices by use case:
  • Biological assays: DMSO stock (e.g., 10–50 mM), diluted into aqueous media; keep final DMSO ≤0.1–0.5% v/v as assay permits.
  • Salt/base interconversion or derivatization: anhydrous DMF/DMAc or dichloromethane with mild base/acid, as appropriate to the transformation.
  • Purification: reverse-phase chromatography (water/acetonitrile with acid modifier) or normal-phase silica with polar eluents (EtOAc/MeOH/CH2Cl2) may be required due to phenolic and basic functionalities.
• Comparison notes (literature): DMSO > DMF ≈ NMP for solubilizing capacity; methanol/ethanol can be acceptable at elevated temperature but may promote etherification/transesterification under strong acid conditions—avoid such conditions.

Storage and Reconstitution

• Storage (item-specific from Product Data): Store at -80°C.

• Shipping (item-specific from Product Data): Shipped on dry ice packs + cold packs.

• Appearance (item-specific): Not specified for this item; refer to CoA/Spec Sheet.

• General reconstitution guidance (literature/good practice):

  • Solid: allow the sealed container to equilibrate to room temperature in a desiccator before opening to prevent moisture condensation.
  • Solubility: dissolve in DMSO to prepare a concentrated stock (e.g., 10–50 mM). For aqueous working solutions, dilute the DMSO stock into buffer with vigorous mixing; slightly acidic buffers can aid solubility for the HCl salt.
  • Filtration: if particulate is observed, filter through 0.22 µm PTFE or PES (avoid cellulose esters if using strong organic cosolvents).
  • Aliquoting: prepare single-use aliquots to avoid repeated freeze–thaw.

• Solution stability (general):

  • DMSO stocks are typically stable for weeks to months at ≤ −20 °C protected from light; verify by LC–MS/HPLC before critical experiments.
  • Avoid prolonged exposure of solutions to light and elevated temperature.

For definitive, lot-specific stability limits and any reconstitution instructions unique to this item, consult the CoA/Spec Sheet and SDS.

Structure and Identity

Raloxifene HCl (raloxifene hydrochloride) is a small-molecule selective estrogen receptor modulator (SERM) provided as the hydrochloride salt for research use.

• Item-specific IDs from Product Data:

  • SKU: R408663
  • CAS: 82640-04-8
  • PubChem CID: 54900
  • InChIKey: Not specified for this item; refer to CoA/Spec Sheet.
  • SMILES: Not specified for this item; refer to CoA/Spec Sheet.

• Structure descriptors (literature):

  • Molecular formula (literature): C28H28ClNO4S (hydrochloride salt)
  • Molecular weight (literature): ~510.05 g/mol (hydrochloride salt)
  • Core features: triphenylethylene-derived scaffold bearing a benzothiophene unit; phenolic hydroxyl groups; a tertiary amine tethered via an ether/alkyl linker; present as the protonated ammonium chloride salt.
  • Functional groups: phenols (two), tertiary amine (as ammonium in HCl salt), ether linkages, benzothiophene heteroaromatic, aryl rings.
  • Stereochemistry: no stereogenic centers (achiral); multiple aromatic rings in a rigid, extended conformation.

• 2D description (literature): a benzothiophene ring system para- and ortho-substituted with phenoxy/alkoxy linkers that connect to a phenolic ring terminating in a tertiary amino side chain; the phenolic OH groups occupy para positions on two aryl rings; the HCl forms an ion pair with the tertiary amine.

Synthetic Utility

Although primarily used as a reference compound, the raloxifene scaffold contains functional handles amenable to late-stage diversification, making it a useful platform in SAR exploration.

• Key reactive sites (literature):
  • Two phenolic OH groups: O-alkylation/acylation to modulate polarity and receptor interactions; carbonate/carbamate formation as protecting/derivatizing strategies.
  • Tertiary amine: salt exchange (HCl ↔ other acids), quaternization for SAR probes, or conversion to amide via dealkylation/realkylation sequences (indirect routes).
  • Benzothiophene/aryl rings: electrophilic substitution (nitration, halogenation) under controlled conditions; cross-coupling feasible on suitably functionalized analogs.
• Retrosynthetic value: serves as a benchmark for SERM chemotypes; derivatives can be prepared by modifying phenolic positions or side-chain amine to probe ER-binding pharmacophores.
• Protecting-group strategy: selective protection of one phenol (e.g., TBDMS vs benzyl) enables orthogonal functionalization; careful base choice avoids competitive deprotonation of both phenols.
• Purification/analysis: reverse-phase HPLC with acidic modifier (0.05–0.1% TFA or formic acid) aids peak shape for basic analytes; LC–MS readily detects [M+H]+ around 510 for the HCl salt equivalent mass-to-charge when considering the free base protonation.

Target Specificity

This section applies primarily to antibodies or affinity reagents; it is not typically applicable to a small-molecule compound like raloxifene HCl.

• No antigen/epitope, species reactivity, clone, or isotype information applies here.
• For biochemical targeting context, see Biological Roles for literature notes on estrogen receptor binding.