MAC glucuronide α-hydroxy lactone-linked SN-38 , CAS No.2246380-70-9

CAS: 2246380-70-9 Cat. No.: M777700 Fórmula: C₅₀H₅₄N₆O₂₀S Peso molecular: 1091.06

Storage

Store at -20°C

Shipped In

Ice chest + Ice pads

Descripción general

MAC glucuronide alpha hydroxy lactone linked SN-38 is a stable lactone compound composed of ADC toxin SN-38 (Topoisomerase I inhibitor) and MAC glucuronide alpha hydroxy lactone. MAC glucuronide α - hydroxy lactone linked SN-38 exhibits cytotoxicity towards L540cy cells and Ramos cells, with IC50 values of 99 and 105 ng/mL, respectively.

Especificaciones

Mecanismos bioquímicos y fisiológicos

MAC glucuronide α-hydroxy lactone-linked SN-38 (Topoisomerase I inhibitor) is a stabilized lactone MAC glucuronide α-hydroxy lactone-linked SN-38 agent linker. MAC glucuronide α-hydroxy lactone-linked SN-38 is cytotoxic across L540cy cells and Ramos cells

Condiciones de almacenamiento de almacenamiento

Store at -20°C

Enviado en

Ice chest + Ice pads

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Nombres e identificadores

Peso molecular

1091.06

Application Protocols

No item-specific tested applications are provided. The following are general, literature-style procedures offered as starting points and should be optimized by the user.

A. Preparation of stock solution

• Warm anhydrous DMSO to room temperature. Dissolve the compound to 10–50 mM with gentle vortexing. Filter through a 0.2 µm PTFE syringe filter if particulates persist. Aliquot and store at −20°C. Avoid repeated freeze–thaw.

B. β-Glucuronidase cleavage assay (HPLC readout)

• Buffer: 50 mM sodium acetate, pH 5.0. Equilibrate to 37°C.
• Setup: In microtubes, combine buffer, enzyme (e.g., 0.05–0.5 U/mL), and substrate (final 1–10 µM; ≤1% DMSO). Include no-enzyme and heat-inactivated controls.
• Incubate: 37°C with gentle mixing. At defined timepoints, quench aliquots with equal volume of ice-cold acetonitrile containing internal standard.
• Analyze: Centrifuge, inject supernatants on LC–MS/MS or HPLC-UV. Quantify intact prodrug and SN-38 using calibration curves.

C. Stability in neutral buffer

• Incubate 5 µM compound in 50 mM phosphate buffer, pH 7.4, 37°C. Sample over 0–24 h; quench and analyze as above to assess non-enzymatic hydrolysis/release.

Notes

• Validate linearity of response and recovery in your matrix. Confirm absence of carryover and adsorption to plastics; pre-rinse tips/tubes with 0.1% DMSO if needed.
• These procedures are general guidance and are not validated for this specific item.

Biological Roles

General/literature context (no clinical claims)

• SN-38 is the active camptothecin-class scaffold known in the literature to interact with DNA topoisomerase I, stabilizing the cleavable complex and interfering with DNA re-ligation in proliferating cells. The prodrug format in this item masks SN-38 through a glucuronide-containing, α-hydroxy lactone-linked construct designed for enzymatic unmasking.
• Glucuronidation is a Phase II biotransformation pathway that enhances polarity and facilitates excretion. β-Glucuronidase, a lysosomal and extracellular enzyme (notably present in certain microenvironments), hydrolyzes glucuronide conjugates to liberate aglycones (literature biology).
• The α-hydroxy lactone linker functions as a self-immolative unit: following enzyme-catalyzed deprotection, intramolecular cyclization/fragmentation can release the parent payload. Such linkers are widely studied for conditional activation of small molecules in chemical biology.
• pH-driven equilibria: The camptothecin E-ring toggles between lactone (acid-favored) and carboxylate (base-favored) forms, which influences membrane permeability, protein binding, and assay readouts. Researchers often control pH and time-in-solution to maintain a defined speciation during experiments.
• Utility as a probe: This conjugate can be used in vitro to investigate enzyme kinetics of β-glucuronidase, evaluate release pathways, and benchmark delivery vehicles that rely on enzymatic triggers. Any observed biological effects should be interpreted in the context of release efficiency and speciation rather than assumed direct action of the intact prodrug.

Buffer Applications

This item is not a buffering reagent and is not used to set or maintain pH. However, buffer choice is critical for its stability and enzymology studies.

General guidance (literature)

• Enzyme assays with β-glucuronidase are commonly conducted in acetate or citrate buffer around pH 4.5–5.5 (optimum may vary by enzyme source). Maintain ionic strength (e.g., 50–100 mM) and include 0.01–0.1% surfactant (Tween-20) only if needed to prevent nonspecific adsorption, verifying no impact on enzyme activity.
• Stability controls are often run in neutral phosphate buffer (pH 7.0–7.4) to assess non-enzymatic hydrolysis. Avoid strongly basic buffers (pH > 8) unless probing lactone opening kinetics, as camptothecin lactones can hydrolyze rapidly at high pH.
• For cell-based exposures, buffered salt solutions (HBSS) or culture media are used with low DMSO content; serum proteins may affect apparent solubility and release.

Recipes (illustrative; verify for your system)

• 50 mM sodium acetate, pH 5.0: 2.05 g sodium acetate trihydrate in 500 mL water, adjust pH with acetic acid, bring to 1 L, filter-sterilize if required.
• 50 mM phosphate buffer, pH 7.4: 3.40 g Na2HPO4·2H2O and 0.39 g NaH2PO4·H2O to 1 L, adjust as needed.

Note: These are general literature recipes for assay development and are not item-specific specifications.

Green Alternatives

While this product itself is a specialized small-molecule conjugate (not replaceable by a generic greener reagent), greener choices can be made in its handling and analysis.

Solvent and process considerations (general guidance)

• Prefer ethanol or water/ethanol mixtures over DMF or acetonitrile when feasible for cleaning and preliminary solubilization, recognizing potential solubility limitations for camptothecin-based conjugates.
• Minimize DMSO content in biological assays to ≤0.1–0.5% v/v where compatible with signal-to-noise requirements. Use concentrated stocks to reduce total solvent introduction.
• Apply microscale experimentation (Design of Experiments, 96-well formats) to reduce chemical use and waste.
• Use solid-phase or cartridge-based sample cleanup to minimize large volumes of chlorinated solvents in analytical workflows.

Comparison (general, not item-specific specifications)

• DMSO vs ethanol: DMSO offers superior solvating power but is less benign environmentally; ethanol is greener but may not reach required concentrations.
• ACN vs MeOH for HPLC: ACN provides better peak shape for hydrophobic analytes but has higher environmental and supply-chain concerns; MeOH is generally greener though may require method re-optimization.

Waste and lifecycle

• Segregate cytotoxic organic waste; avoid halogenated solvents. Adopt closed transfer systems to reduce operator exposure and fugitive emissions.
• Consider lyophilization of aqueous aliquots (if compatible) to extend shelf-life and reduce repeat solvent usage (validate stability first).

Pharmaceutical Uses

No clinical or therapeutic claims are made. This product is for research use only.

Formulation and development context (general, literature-based)

• Prodrug/linker–payload systems like glucuronide–α-hydroxy lactone–SN-38 are studied in formulation research as model compounds for enzyme-triggered release. They are used to evaluate excipients, carriers, and manufacturing conditions that impact stability and release (e.g., pH, ionic strength, surfactants).
• Potential roles in preformulation studies include: solubility screening across pH, cosolvent mapping (DMSO, ethanol, PEG 400), and compatibility with liposomes, polymeric micelles, or nanoparticles for non-covalent loading.
• Reference standards: Employed as analytical standards to develop stability-indicating HPLC/LC–MS methods distinguishing intact prodrug, released SN-38, and linker byproducts under ICH-like stress conditions (acid/base, oxidative, thermal, photolytic) for research purposes.
• Excipients: Typical screening includes polysorbates, poloxamers, and cyclodextrins to enhance apparent solubility; their selection is guided by minimizing prodrug degradation and maximizing release predictability during in vitro tests.

Regulatory status

• No pharmacopeial monograph is indicated for this specific conjugate. GMP status is not claimed. For any work intersecting regulated development, obtain appropriate quality documentation and perform in-house qualification of the material.

Physical Properties

Item-specific numerical properties

• Appearance: Not specified for this item; refer to CoA/Spec Sheet.
• Purity/Grade: Not specified for this item; refer to CoA/Spec Sheet.
• Molecular weight: Not specified for this item; refer to CoA/Spec Sheet.
• Molecular formula: 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 (thermally labile organic; decomposition likely before boiling under ambient pressure). Not specified for this item; refer to CoA/Spec Sheet.
• Density, refractive index, pKa, logP/logD, UV cutoff: Not specified for this item; refer to CoA/Spec Sheet.

General/literature-based discussion (not item specifications)

• Camptothecin analogs typically exhibit poor aqueous solubility as the closed lactone; conjugation with a glucuronide and an α-hydroxy lactone linker can enhance polarity and aqueous compatibility, especially in the open-carboxylate state at neutral–basic pH.
• The camptothecin E-ring lactone is known to hydrolyze to a carboxylate under basic conditions and revert to the lactone under acidic conditions (literature behavior). Linker design can influence this equilibrium and overall stability.
• Solubility handling: Stocks are commonly prepared in anhydrous DMSO and diluted into buffered media immediately before use to minimize premature hydrolysis. Co-solvents such as ethanol or DMF may be used as needed. Actual solubility limits for this specific conjugate are not available here; determine empirically.
• Spectroscopic features: Aromatic chromophores in camptothecin scaffolds absorb in the UV range; exact λmax and ε for this conjugate are not specified and should be determined experimentally or obtained from the CoA/SDS where available.

Quality and Grades

• Grade/Purity: Not specified for this item; refer to CoA/Spec Sheet. In the absence of an explicit grade (e.g., ≥98% by HPLC), users should consult the CoA for assay method, purity, and impurity profile.
• Research use only: The listing is explicitly for research use only. Not for diagnostic or therapeutic use, not for human or animal administration.
• What “research-grade” typically implies (general):
  • Analytical characterization by HPLC/LC–MS and/or NMR to confirm identity and purity suitable for laboratory research.
  • No guarantee of endotoxin/bioburden limits or GMP compliance.
  • UV absorbance background and residual solvent levels are not controlled to chromatographic-grade solvent specifications unless stated.
• Stabilizers/additives: Not specified for this item; refer to CoA/Spec Sheet. If present in certain camptothecin formulations (e.g., acid stabilizers), they would be listed on the CoA.
• Batch-to-batch considerations:
  • Camptothecin derivatives can exhibit polymorphism and variable residual solvent; verify with incoming QC if your application is sensitive.
  • Verify lactone:carboxylate ratio as relevant to your assay conditions (literature note). If critical, consider immediate use after dissolution and standardize pH.
• Documentation: For regulated studies, retain the CoA, lot-specific chromatograms, and any residual solvent reports supplied with the item. Request additional analytics from Aladdin Scientific support if needed.

Reaction and Applications

This product is primarily a small-molecule research tool/prodrug conjugate rather than a synthetic reagent. The most relevant applications are biochemical and stability/activation studies rather than classic synthetic transformations.

Applications (literature/general)

• Enzyme-triggered release studies: The glucuronide trigger enables evaluation of β-glucuronidase-mediated cleavage, followed by self-immolative fragmentation through the α-hydroxy lactone linker to liberate SN-38. Useful in studying tumor- or microenvironment-associated enzymatic activity in vitro (research context).
• Prodrug stability profiling: Assess pH-dependent stability (lactone vs carboxylate), serum stability, and half-life in buffer with/without glucuronidase.
• Analytical method development: LC–MS/MS and HPLC-UV methods to separate prodrug, released SN-38, and linker fragments; determination of kinetic parameters (pseudo-first-order rate constants) under varying enzyme concentrations.
• Conjugation platform evaluation: Although supplied as a standalone small molecule, it can serve as a model payload-linker system to benchmark ADC, polymer–drug conjugate, or nanoparticle release behaviors (using non-covalent loading or post-loading strategies).

Practical notes

• Maintain solutions cold and protected from light where feasible; prepare fresh working dilutions.
• Control pH carefully during incubations to avoid unintended lactone opening.
• Include appropriate controls: no-enzyme (stability), heat-inactivated enzyme, and authentic SN-38 standard to calibrate release quantitation.

Not typical for: Cross-coupling, Grignard, or other classic synthetic reactions. If chemical derivatization is intended, confirm reactive handles and protection strategy from the CoA/structure.

Reaction Conditions

Because this product is primarily for biochemical activation and stability studies, “reaction conditions” center on enzymatic cleavage and hydrolysis rather than synthetic transformations. The following are general literature guidelines (not item specifications):

β-Glucuronidase-mediated cleavage

• Buffer: 50 mM sodium acetate, pH 4.5–5.5 (optimum depends on enzyme source).
• Temperature: 25–37°C.
• Enzyme: Typical working concentrations span 0.01–1 U/mL for kinetic studies; adjust to maintain initial-rate conditions.
• Substrate: Prepare 10×–100× concentrated DMSO stocks; final organic content ≤1%.
• Readout: LC–MS/MS or HPLC-UV quantifying disappearance of prodrug and appearance of SN-38; include time-zero and no-enzyme controls.

Chemical hydrolysis (pH dependence)

• Acidic stability: pH 4–6 tends to favor the camptothecin lactone; monitor for slower hydrolysis.
• Basic hydrolysis: pH ≥8 accelerates E-ring opening and may also affect linker integrity; perform short incubations on ice if basic conditions are required.

Photostability and temperature

• Protect from strong light to limit photodegradation of aromatic systems (general for camptothecins). Conduct kinetic assays at controlled temperature with pre-equilibrated buffers.

Typical outcomes (literature)

• First-order or pseudo-first-order kinetics often describe initial cleavage/hydrolysis phases. Half-lives can vary from minutes to hours depending on pH, enzyme level, and matrix. Determine parameters empirically for your system.

Safety and Handling

Authoritative safety information must be taken from the product SDS. The following summarizes general precautions for camptothecin-derived research chemicals and glucuronide prodrugs:

Item-specific hazard data

• Signal word: Not specified for this item; refer to SDS.
• H-statements: Not specified for this item; refer to SDS.
• GHS classification: Not specified for this item; refer to SDS.
• Pictograms: Not specified for this item; refer to SDS.

General handling guidance (literature/practice)

• Potential hazards: Camptothecin derivatives and their prodrugs are often cytotoxic and genotoxic in vitro. Avoid inhalation, ingestion, skin/eye contact. Handle as a hazardous research chemical in a certified chemical fume hood or biosafety cabinet appropriate for small-molecule cytotoxins.
• PPE: Lab coat, double nitrile gloves, safety glasses or face shield. Change outer gloves frequently; use absorbent pads and dedicated tools to minimize contamination.
• Engineering controls: Handle powders with containment (weighing funnels, antistatic measures). Use closed transfer for DMSO stocks when possible.
• Incompatibilities: Strong bases can promote lactone opening and potential degradation; strong oxidants may degrade aromatic systems; avoid prolonged exposure to light and elevated temperature.
• Spill/first aid (overview): For small spills, absorb with inert material, collect as hazardous waste. In case of skin contact, wash with soap/water; eye contact, rinse with water for 15 minutes and seek medical attention; inhalation, move to fresh air; ingestion, seek medical attention. Defer to SDS for detailed procedures.
• Waste: Dispose as halogen-free organic hazardous waste unless otherwise directed by institutional EHS. Decontaminate surfaces with suitable organic solvents followed by detergent/water.
• Shipping/storage: Shipped cold (ice chest + ice pads). Store at −20°C as specified. Avoid freeze–thaw of solutions; prepare single-use aliquots.

Solvent Selection

General solvent behavior (literature; not item specifications)

• Polarity/miscibility: The SN-38 scaffold is hydrophobic in the closed-lactone form; the appended glucuronide and α-hydroxy lactone linker increase polarity. As a result, the conjugate often dissolves well in polar aprotic solvents (DMSO, DMF) and may show limited to moderate aqueous solubility depending on pH and ionic state.
• Recommended stock solvents: Anhydrous DMSO is the most common choice for concentrated stocks (e.g., 10–50 mM). Ethanol or acetonitrile can be used for intermediate solubility; aqueous buffers typically require a co-solvent fraction (e.g., 0.5–5% DMSO) to avoid precipitation.
• pH considerations: Camptothecin lactones favor the closed form at acidic pH; basic conditions open the lactone to a carboxylate, which can improve apparent aqueous solubility but may alter behavior. Keep assay pH consistent and minimize preincubation time in basic media unless specifically studying hydrolysis.
• Additives: Inclusion of cyclodextrins or serum proteins can increase apparent solubility of camptothecin derivatives (literature). Validate compatibility with your assay.

When to choose alternatives

• For purely aqueous systems with minimal organic content, consider preparing dilute stocks in DMSO and immediate dilution into buffered media containing carrier protein (e.g., 0.1% BSA) to avoid precipitation. If strictly solvent-free conditions are needed, investigate liposomal or micellar carriers.

Quick comparison (general)

• DMSO: maximal solvating power, biologically tolerated at low %; hygroscopic, can carry water that promotes hydrolysis.
• DMF/ACN: good solvents for method development and analytics; consider toxicity and volatility.
• Ethanol: greener, volatile, but may have lower solubility capacity for this conjugate.

Storage and Reconstitution

Item-specific storage conditions

• Storage: Store at −20°C (per Product Data). Maintain in the original, tightly closed container.
• Shipping: Shipped in an ice chest with ice pads (per Product Data).

General best practices (not item specifications)

• Protect from moisture and prolonged light exposure. Allow the vial to warm to room temperature in a desiccator before opening to avoid condensation.
• For reconstitution, prepare concentrated stocks in anhydrous DMSO (e.g., 10–50 mM). Mix gently to dissolve. If necessary, sonicate briefly in a room-temperature water bath. Filter through a 0.2 µm PTFE filter if particulates remain.
• Aliquot stocks into single-use vials or low-bind microtubes; refreeze promptly at −20°C or below. Avoid multiple freeze–thaw cycles of the same aliquot.
• Working solutions in aqueous buffers should be prepared immediately before use and kept on ice or at the defined assay temperature. Discard unused diluted solutions after the experiment; stability in water is system- and pH-dependent.
• Label aliquots with lot number, concentration, solvent, and date of preparation. Periodically verify integrity by HPLC/LC–MS.

Note

• Appearance, solubility limits, and any stabilizers are not specified for this item; refer to the CoA/Spec Sheet and SDS for definitive handling instructions.

Structure and Identity

• Item name: MAC glucuronide α-hydroxy lactone-linked SN-38 (SKU: M777700)
• CAS: 2246380-70-9
• 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 description (general, literature-based):

• The core payload is SN-38, a camptothecin-class pentacyclic alkaloid featuring a fused quinoline/indolizino[1,2-b]quinoline skeleton with an E-ring lactone. SN-38 bears a phenolic OH (at C10 in literature notation) and a tertiary lactone that is sensitive to pH-dependent opening.
• The “glucuronide α-hydroxy lactone-linked” designation indicates a sugar-derived protective/triggering group (glucuronic acid) attached via a self-immolative linker to the SN-38 scaffold. The α-hydroxy lactone motif typically resides within the linker, enabling β-glucuronidase-triggered cleavage followed by lactonization/fragmentation to release SN-38 (literature concept for glucuronide prodrugs). Specific connectivity (O- vs N-link, site of attachment on SN-38) is not specified here; consult CoA/Spec Sheet.
• Expected functional groups (general): lactone (E-ring), phenolic ether/ester linkage through the linker, a glucuronic acid moiety (often as a β-glucuronide trigger in literature), and multiple aromatic rings with a tertiary amine-like lactam-lactone system characteristic of camptothecins.
• Stereochemistry: Camptothecin scaffolds possess defined stereocenters critical for activity; this item’s absolute configuration and any anomeric configuration on the glucuronide are not specified here; refer to CoA/Spec Sheet.

Synthetic Utility

This material is supplied as a finalized conjugate and is not typically employed as a building block in multi-step organic synthesis. Nevertheless, it can play roles in method development and mechanistic studies:

• Mechanistic probe: Serves as a model for studying self-immolative linker fragmentation pathways (α-hydroxy lactone cascades) under enzymatic and chemical triggers. Results can inform design of new linkers and protecting groups.
• Analytical benchmarking: Validates derivatization protocols (e.g., enzymatic or mild chemical deprotection) and subsequent quantification of released aglycone (SN-38) for LC–MS workflows.
• Kinetic modeling: Provides data for fitting Michaelis–Menten or first-order release models in the presence of β-glucuronidase or in buffered hydrolysis, informing structure–release relationships for related conjugates.

Not typically applicable

• It is not generally used in cross-coupling, nucleophilic substitutions, or carbon–carbon bond-forming sequences. Its multiple functional groups (lactone, glycosidic linkage) and potential lability make it a poor substrate for harsh conditions.

If derivatization is contemplated

• Any attempt to further functionalize should consider protection of the glucuronide and maintenance of the E-ring lactone. Reaction conditions should be mild (ambient temperature, neutral pH, anhydrous) to avoid premature hydrolysis. Structural confirmation by high-resolution MS and 2D NMR is recommended after any modification.

Target Specificity

Not applicable. This product is a small-molecule conjugate and is not an antibody, oligonucleotide, or biologic with defined antigen/epitope specificity. If used as a chemical biology probe, its functional “target” in literature terms is the enzymatic trigger (β-glucuronidase) governing release, and subsequently the well-known biochemical interactions of SN-38; however, no target specificity data are provided for this catalog item.