Hydrocortisone cypionate - 10mM in DMSO , Glucocorticoid receptor agonist, CAS No.508-99-6, Glucocorticoid receptor agonist

CAS: 508-99-6 Cat. No.: H655360 Formula: C₂₉H₄₂O₆ Peso molecolare: 486.64 PubChem CID: 223253

GRADE & PURITY 10mM in DMSO

Storage

Store at -80°C

Shipped In

Dry ice packs + Cold packs

Panoramica

Hydrocortisone cypionate is a synthetic glucocorticoid corticosteroid and a corticosteroid ester.

In Vitro

Hydrocortisone (50 nM) shows a dose-dependent down-regulation of GR transcript in hCMEC/D3 cells. Hydrocortisone supplementation of the serum-reduced cell differentiation medium leads to a significant increase in TER across the hCMEC/D3 monolayer. Hydrocortisone-treated Dendritic cells (DCs) show a decreased expression of MHC II molecules, the costimulatory molecule CD86, and the DC-specific marker CD83, as well as a strongly reduced IL-12 secretion. Hydrocortisone-treated DCs inhibit production of IFN-γ but induce an increased release of IL-4 and no change in IL-5. Hydrocortisone reduces postischemic oxidative stress, perfusion pressure, and transudate formation. Hydrocortisone inhibits postischemic shedding of syndecan-1, heparan sulfate, and hyaluronan as is release of histamine from resident mast cells. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Specifications

Specifiche e purezza

10mM in DMSO

Meccanismi biochimici e fisiologici

Hydrocortisone cypionate is a synthetic glucocorticoid corticosteroid and a corticosteroid ester.

Condizioni di conservazione di stoccaggio

Store at -80°C

Spedito in

Dry ice packs + Cold packs

Questo prodotto richiede spedizione a catena fredda. I servizi di terra e altri servizi economici non sono disponibili.

Tipo di azione

AGONIST

Meccanismo d'azione

Glucocorticoid receptor agonist

Proprietà del prodotto

ALogP

4.7

Nomi e identificatori

Isomeri SMILES

C[C@]12CCC(=O)C=C1CC[C@@H]3[C@@H]2[C@H](C[C@]4([C@H]3CC[C@@]4(C(=O)COC(=O)CCC5CCCC5)O)C)O

PubChem CID

223253

Peso molecolare

486.64

Application Protocols

No item-specific, validated application protocols are provided. The following general laboratory practices are commonly used for lipophilic small molecules like hydrocortisone cypionate (literature/general):

• Stock solution preparation:
  • Weigh quickly to minimize ambient moisture exposure. Dissolve in anhydrous DMSO to prepare a 10–50 mM stock. Vortex and, if needed, sonicate briefly. Filter (0.22 µm PTFE) for sterile applications.
  • Alternative solvents: Ethanol or DMF if DMSO is incompatible with the assay; verify solubility and assay tolerance.
• Working solutions for cell-based assays:
  • Dilute DMSO stock into pre-warmed culture medium to achieve final DMSO ≤0.1–0.5% v/v. Mix thoroughly to avoid localized precipitation. Include vehicle controls at matched DMSO.
  • For hydrolysis-dependent studies, preincubate with esterases or serum as required and confirm conversion to hydrocortisone by LC–MS.
• Enzyme kinetics (esterase assays):
  • Buffer: 50 mM HEPES or PBS, pH 7.4; 37 °C. Start reaction by adding enzyme to substrate (10–200 µM). Quench at time points with ice-cold MeCN containing internal standard. Analyze by LC–MS for parent/acid/alcohol.
• Stability checks:
  • Conduct short-term stability in assay matrix (1–24 h) at target temperature to ensure reproducible exposure.
• Note: These are general guidelines only and not validated for this specific item; adjust per institutional SOPs.

Biological Roles

The following reflects literature/general biochemical context for hydrocortisone esters; not product-specific and not clinical.

• Mechanistic role (literature/general):
  • Hydrocortisone cypionate is a 21‑O‑ester that increases lipophilicity and can serve as a pro‑form of hydrocortisone. After enzymatic or chemical hydrolysis, hydrocortisone engages the glucocorticoid receptor (GR) to modulate gene transcription in experimental systems.
• ADME-relevant features (research context):
  • Increased hydrophobicity favors membrane partitioning and depot-like behavior; the cypionate chain slows aqueous dissolution and can modulate hydrolysis rates by esterases.
  • Protein binding in serum and partitioning into lipid phases are typically higher vs the parent alcohol (qualitative expectation for long-chain esters).
• Enzymatic pathways (literature/general):
  • Hydrolysis by carboxylesterases and nonspecific esterases yields hydrocortisone + cyclopentylpropionic acid; subsequent metabolism of hydrocortisone follows classical 11β‑HSD and hepatic reductase pathways.
• Experimental readouts:
  • Reporter gene assays, GR nuclear translocation, and GRE-driven transcription can be used to compare activity of the ester vs parent after hydrolysis.
• Caution:
  • Avoid inferring therapeutic properties from in vitro activity; this product is for research use only. Potent biological effects are possible; handle with care to prevent unintended exposure.

Buffer Applications

This item is not a buffer reagent. It has very low aqueous solubility and does not serve as a pH buffer. For biological experiments, prepare concentrated stocks in DMSO or ethanol and dilute into pre-made buffers (e.g., PBS, HBSS) with minimal organic cosolvent (general practice). Refer to Solvent Selection and Application Protocols for practical guidance.

Green Alternatives

Opportunities to improve the sustainability profile when handling or synthesizing hydrocortisone cypionate focus on solvent choice and reaction conditions (literature/general).

• Greener solvent substitutions:
  • Replace dichloromethane/chloroform with ethyl acetate or 2‑MeTHF for extractions and chromatography where feasible.
  • Use ethanol or isopropanol in place of methanol when solubility permits, to reduce toxicity.
  • For coupling/esterification steps, 2‑MeTHF or CPME can substitute for DCM with comparable performance in DMAP-mediated acylations.
• Process considerations:
  • Enzymatic esterification/transesterification in green solvents or solvent-free systems can reduce waste and avoid strong acid chlorides.
  • Employ catalytic rather than stoichiometric bases (e.g., DMAP, imidazole) and minimize carbodiimide byproducts by adopting greener coupling reagents or acid anhydrides.
• Comparison table (general guidance):
  • DCM/CHCl3: Excellent solvency for steroids; high environmental/health impact; chlorinated waste stream.
  • 2‑MeTHF/CPME: Good solvency for hydrophobic steroids; bio-based (2‑MeTHF), better safety; requires peroxide monitoring over time.
  • Ethyl acetate: Readily biodegradable, low toxicity; may require larger volumes due to moderate solvency.
• Waste minimization:
  • Use mini-columns or dry-loading for chromatography to cut solvent use; apply gradient scouting to shorten runs.
  • Recover and reuse ethyl acetate/heptane blends by fractional distillation where permitted.

Pharmaceutical Uses

No medical or clinical claims are made. The following points reflect formulation science concepts from the literature/general knowledge for steroidal esters.

• Role in formulation research (literature/general):
  • 21‑Esterification increases lipophilicity and is used to study depot behavior, release kinetics, and solubility in oil-based vehicles and polymeric depots.
  • Cypionate esters are classical models for prolonged release properties due to steric hindrance around the ester and hydrophobic chain.
• Excipient compatibility (general):
  • Frequently soluble in pharmaceutically acceptable solvents/oils (e.g., benzyl benzoate, medium-chain triglycerides) in research settings; compatibility must be verified experimentally.
  • Sensitive to hydrolysis under alkaline aqueous conditions; avoid aqueous excipients unless stabilized and used promptly.
• Analytical development:
  • Quantified by HPLC/UPLC with UV detection (absorption near 240–250 nm) or LC–MS/MS, employing internal standards to track potential hydrolysis to hydrocortisone.
• Regulatory note:
  • This catalog item is for research use only and not manufactured to GMP specifications. It is not intended for human or veterinary use.

Physical Properties

Item-specific specifications are not provided in the Product Data. The following notes are general/literature guidance for hydrocortisone 21‑cypionate; consult the CoA/SDS for authoritative values.

• Appearance (item-specific): Not specified for this item; refer to CoA/Spec Sheet.
• Molecular weight and formula: Not specified for this item; refer to CoA/Spec Sheet.
• Melting point (literature/general): Steroidal 21‑esters of hydrocortisone are typically crystalline solids with melting points often in the 180–230 °C range, depending on solvate/hydrate form and ester chain. Specific MP for this compound should be verified on the CoA.
• Solubility (literature/general):
  • Readily soluble in polar aprotic organic solvents such as DMSO and DMF at millimolar concentrations.
  • Moderately soluble in alcohols (methanol, ethanol) and chlorinated solvents (DCM, chloroform); poor aqueous solubility expected due to lipophilic cypionate ester.
• Partitioning (literature/general): Lipophilicity significantly increased vs hydrocortisone; logP is expected to be higher than the parent alcohol, favoring membrane permeability and depot behavior. Numeric logP not stated here; verify with supplier/literature if required.
• UV/Vis (literature/general): Typical steroid Δ4‑3‑ketone shows a UV absorption band around 240–250 nm; specific UV cutoff or ε not established for this item.
• Density/refractive index: Not applicable for a solid; not specified for this item.
• Hygroscopicity/photostability (literature/general): Generally light-sensitive to prolonged UV exposure; avoid moisture to prevent slow hydrolysis of the ester.

Quality and Grades

• Item-specific grade/purity: Not specified for this item; refer to CoA/Spec Sheet.
• What grade means (general guidance):
  • Research-grade small molecules are typically supplied at high chemical purity suitable for discovery chemistry, analytical characterization, and in vitro studies. If an HPLC/LC–MS purity is reported on the CoA, it denotes chromatographic area % under defined conditions and does not guarantee absence of bioinert inorganic residues unless stated.
  • Residual solvent, water content (Karl Fischer), and inorganic impurities (metals) are not guaranteed unless explicitly specified on the CoA/specification.
• Stabilizers: Not specified for this item; refer to CoA/Spec Sheet. Steroidal esters are commonly supplied neat without stabilizers; if an antioxidant or desiccant is used in packaging, it will be noted on the CoA.
• Documentation and verification:
  • For regulated or quantitative applications (e.g., reference standard work), request a batch-specific CoA including identity confirmation (1H/13C NMR, HRMS), purity by HPLC/UPLC, and where applicable residual solvent/water.
  • If chirality/stereochemistry is critical, ensure spectral data are consistent with the natural hydrocortisone configuration and the 21‑O‑ester substitution pattern (general best practice).

Reaction and Applications

This compound is primarily a lipophilic pro‑ester of hydrocortisone. It is used in research as a chemical tool and substrate in studies of ester stability, enzymatic hydrolysis, and steroid receptor engagement (non-clinical, laboratory applications only).

• Research applications (literature/general):
  • Enzymology: Substrate for esterase/carboxylesterase and lipase-mediated hydrolysis to hydrocortisone; kinetic profiling under physiological and non-physiological conditions.
  • Receptor biology: Ligand for glucocorticoid receptor studies after in situ or in cellulo hydrolysis; comparative potency vs parent alcohol can be assessed in reporter assays.
  • Formulation science: Model steroid ester for depot/release investigations in biodegradable matrices and microspheres.
• Synthetic transformations (literature/general):
  • Selective deprotection/hydrolysis at C‑21 to regenerate hydrocortisone under mild basic conditions (e.g., MeOH/K2CO3, enzymatic hydrolysis), typically retaining the 11β‑OH and 17α‑OH functionalities.
  • Transesterification to alternate 21‑esters using acid chlorides/anhydrides in the presence of DMAP/NEt3 under anhydrous conditions.
  • Oxidation/reduction at non-ester positions (e.g., selective protection of diols, 11‑keto/11β‑OH interconversions) with 21‑ester serving as a protecting group.
• Practical tips:
  • Carefully control water content during reactions to suppress premature hydrolysis; use dry solvents and molecular sieves as needed.
  • Monitor by HPLC or LC–MS; the parent hydrocortisone (more polar) provides a convenient marker peak in hydrolysis/transesterification workflows.

Reaction Conditions

General literature-style guidance for common manipulations of hydrocortisone 21‑esters; verify and optimize for your system.

• Esterification to form the cypionate (from hydrocortisone):
  • Reagents: Cyclopentylpropionyl chloride or the corresponding anhydride; catalytic DMAP; base such as NEt3 or pyridine.
  • Solvent: Anhydrous DCM, THF, or 2‑MeTHF.
  • Temperature/time: 0 °C to rt, 2–16 h. Monitor by TLC (DCM/MeOH 95:5) or HPLC; quench with aqueous NaHCO3.
  • Notes: Protect 11β/17α‑OH if over-acylation is problematic; otherwise, sterics often favor selective 21‑O‑acylation.
• Hydrolysis (deprotection to hydrocortisone):
  • Basic: MeOH or THF/H2O with K2CO3 or Na2CO3 (0.1–0.5 equiv), 0–25 °C, 0.5–4 h; avoid strong base to prevent enone isomerization.
  • Enzymatic: Porcine liver esterase or lipases in buffered aqueous/organic biphasic systems at pH 7–8, 25–37 °C; good selectivity and milder conditions (literature/general).
• Analytical monitoring:
  • LC–MS with APCI/ESI+; UV at 242–248 nm captures the Δ4‑3‑ketone chromophore. Track appearance of hydrocortisone as a more polar product peak.
• Purification:
  • Flash silica using hexanes/EtOAc or DCM/MeOH gradients; minimize basic additives to avoid hydrolysis. Reverse-phase prep HPLC is effective for final polishing.
• Expected yields (literature/general):
  • 21‑O‑acylation of hydrocortisone to long-chain esters commonly provides good to excellent yields (60–85%) after optimization.

Safety and Handling

Always consult the SDS for definitive, product-specific safety information.

• GHS classification (item-specific): Not specified for this item; refer to SDS.
• Signal word, hazard statements, pictograms (item-specific): Not specified for this item; refer to SDS.
• General hazards (literature/general):
  • Low volatility organic solid; dust may be irritating to the respiratory tract, eyes, and skin.
  • As a bioactive steroid, avoid ingestion, inhalation, or skin absorption; handle in a chemical fume hood and minimize exposure.
  • Ester hydrolysis can generate hydrocortisone; treat as a potent small-molecule research chemical.
• PPE and engineering controls (good laboratory practice):
  • Wear lab coat, nitrile gloves, and safety glasses; consider double-gloving when weighing powders.
  • Work in a fume hood; avoid generating dust/aerosols. Use dedicated spatulas/boats for potent compounds.
• Incompatibilities (literature/general):
  • Strong acids or bases may catalyze ester hydrolysis; strong oxidizers may react with the steroidal framework.
  • Protect from light and moisture to limit degradation.
• First-aid overview (general):
  • Inhalation: Move to fresh air; seek medical attention if symptoms persist.
  • Skin/eye contact: Rinse with water for at least 15 minutes; remove contaminated clothing; obtain medical advice.
  • Ingestion: Rinse mouth; do not induce vomiting; seek medical attention.
• Spill and disposal (general):
  • Avoid dust; gently sweep/HEPA vacuum solids. Dispose according to institutional and local regulations for organic research chemicals.

Solvent Selection

Hydrocortisone cypionate is a lipophilic steroidal ester. Solvent choice focuses on dissolving capacity, chemical stability (avoiding hydrolysis), and compatibility with the intended assay or synthesis.

• Polarity and miscibility (literature/general):
  • Highly soluble in DMSO and DMF; good solubility in acetone, ethyl acetate, chloroform, and dichloromethane; limited in acetonitrile; poor in water.
  • Alcohols (MeOH/EtOH) can dissolve the compound but may accelerate hydrolysis in the presence of acid/base or moisture over time.
• Practical selection by use case:
  • Biological assays: Prepare concentrated DMSO stocks (e.g., 10–50 mM) and dilute into aqueous buffers with final DMSO ≤0.1–0.5% v/v to minimize solvent effects (general practice).
  • Purification: Normal-phase silica with hexanes/ethyl acetate or DCM/MeOH; reverse-phase preparative LC with MeCN/H2O (0.1% formic acid or neutral buffers) can be used, noting potential on-column hydrolysis.
  • Storage solutions: Anhydrous DMSO or EtOH in amber vials under inert atmosphere to minimize oxidation/hydrolysis.
• Stability considerations:
  • Avoid prolonged exposure to strong protic/alkaline media; ester linkages are base- and acid-labile.
  • Protect from light during chromatographic handling; the Δ4‑3‑ketone can show UV sensitivity.
• Comparison (literature/general):
  • DMSO vs DMF: DMSO preferred for bioassays due to lower toxicity to cells at small volumes; DMF is acceptable for synthesis but less favored in biology.
  • DCM/CHCl3 enable rapid dissolution for extractions, but not suitable for aqueous dilutions.

Storage and Reconstitution

• Item-specific storage and shipping (from Product Data):
  • Storage Conditions: Store at -80°C.
  • Shipped In: Dry ice packs + Cold packs.
• General handling recommendations (literature/best practice):
  • Upon receipt, keep frozen. Allow the unopened container to equilibrate to room temperature in a desiccator before opening to avoid condensation.
  • Protect from light and moisture. Reseal promptly under inert gas if possible.
• Solid storage:
  • Keep in amber, tightly sealed vials with desiccant at -80 °C for long-term stability. For frequent access, consider a -20 °C working aliquot and maintain the main stock at -80 °C.
• Reconstitution to stock solutions (general):
  • Prepare concentrated stocks in anhydrous DMSO (typical 10–50 mM). Alternatively, use ethanol or DMF if compatible. Label aliquots with solvent, concentration, lot, and date.
  • Filter sterilize through 0.22 µm PTFE for cell-based work if required. Avoid aqueous solutions except for immediate use due to ester hydrolysis.
• Aliquoting and freeze–thaw:
  • Dispense single-use aliquots to minimize freeze–thaw cycles. Store aliquots at -20 to -80 °C as appropriate; avoid repeated temperature cycling.
• Shelf life:
  • Specific retest/expiry is not provided; refer to the CoA/Spec Sheet. Periodically verify integrity by HPLC/LC–MS, monitoring for hydrolysis to hydrocortisone.

Structure and Identity

Brief overview: Hydrocortisone cypionate is a steroidal 21‑ester of hydrocortisone (cortisol) with the cypionate (cyclopentylpropionate) moiety, increasing lipophilicity and hydrophobic depot character (literature/general).

• Item-specific identifiers (from Product Data)
  • SKU: H655360
  • CAS: 508-99-6
  • Category: Small molecules and compound library (研究/实验用途)
  • Research Use: For research use only
• Structure descriptors
  • 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 (literature/general)
  • Core scaffold: tetracyclic cyclopentanoperhydrophenanthrene (steroidal) skeleton of hydrocortisone with a Δ4-3‑ketone in ring A.
  • Functional groups: 3‑one, 11β‑hydroxyl, 17α‑hydroxyl, and an esterified 21‑hydroxyl bearing a cypionate (cyclopentylpropionate) chain; typical 20‑keto/21‑alcohol functionality masked as the 21‑ester.
  • Stereochemistry: Multiple defined stereocenters consistent with natural hydrocortisone configuration (e.g., 8β/9α/10β/13β/14α/17α), with retention at C‑21 under esterification (literature/general).
  • 2D description: three fused six-membered rings (A–C) and a five-membered D ring; a side chain at C‑17 bearing 20‑keto/21‑O‑cypionate; axial/equatorial hydroxyls at C‑11 and C‑17.
• Synonyms (literature/general)
  • Hydrocortisone 21‑cypionate; Cortisol cypionate; Hydrocortisone cyclopentylpropionate.

Synthetic Utility

Hydrocortisone cypionate is valuable both as a protected intermediate and as a substrate for derivatization in steroid chemistry (literature/general).

• Protecting-group behavior:
  • The 21‑O‑cypionate masks the primary alcohol, improving organic solubility and enabling selective transformations at the 11β‑OH, 17α‑OH, or the A‑ring enone without interference from the 21‑OH.
• Transformations:
  • Hydrolysis (neutral to mildly basic, or enzymatic) to regenerate hydrocortisone in late-stage deprotection sequences.
  • Transesterification to other 21‑esters (acetate, butyrate, valerate) to tune physicochemical properties.
  • Selective silylation or acylation of the 11β/17α‑diol while maintaining the 21‑ester, followed by deprotection.
  • Conjugate additions or selective reductions on the Δ4‑3‑ketone after appropriate protection strategies (e.g., formation of 3‑enol ether/ketal if required).
• Retrosynthetic perspective:
  • Typically prepared from hydrocortisone via activation of cyclopentylpropionic acid (cypionic acid) as the acid chloride or mixed anhydride, with DMAP catalysis; reaction is chemoselective for the primary 21‑OH under controlled conditions.
• Practical notes:
  • Control moisture stringently; 21‑esters hydrolyze faster than secondary esters. Use dry, hindered bases (NEt3, DIPEA) and catalytic DMAP; monitor by TLC/HPLC against authentic hydrocortisone.

Target Specificity

Not an antibody or protein reagent; target specificity metadata (antigen, clone, isotype, species reactivity) do not apply. For receptor biology studies, see Biological Roles, which discusses general interactions of the hydrolyzed parent (hydrocortisone) with the glucocorticoid receptor in research contexts.