Gabapentin enacarbil - Moligand™, 10 mM in DMSO , CAS No.478296-72-9

CAS: 478296-72-9 Cat. No.: G1498489 分子式: C₁₆H₂₇NO₆ 分子量: 329.39 EC番号: 620-082-7

GRADE & PURITY Moligand™, 10 mM in DMSO

Storage

Protected from light,Argon charged,Store at -80°C

Shipped In

Dry ice packs + Cold packs

概要

Gabapentin enacarbil (XP-13512) is a prodrug for the anticonvulsant and analgesic drug gabapentin.IC50 Value:Target: Calcium Channel Gabapentin enacarbil is an actively transported prodrug of gabapentin that provides sustained dose-proportional exposure to gabapentin and predictable bioavailability.in vitro: The prodrug (XP-13512) demonstrated active apical to basolateral transport across Caco-2 cell monolayers and pH-dependent passive permeability across artificial membranes. XP13512 inhibited uptake of (14)C-lactate by human embryonic kidney cells expressing monocarboxylate transporter type-1, and direct uptake of prodrug by these cells was confirmed using liquid chromatography-tandem mass spectrometry. XP13512 inhibited uptake of (3)H-biotin into Chinese hamster ovary cells overexpressing human sodium-dependent multivitamin transporter (SMVT) .in vivo:In 4 studies of healthy volunteers (136 subjects total), the pharmacokinetics of XP13512 immediate- and extended-release formulations were compared with those of oral gabapentin. XP13512 immediate-release (up to 2800 mg single dose and 2100 mg twice daily) was well absorbed (>68%, based on urinary recovery of gabapentin), converted rapidly to gabapentin, and provided dose-proportional exposure, whereas absorption of oral gabapentin declined with increasing doses to <27% at 1200 mg. Compared with 600 mg gabapentin, an equimolar XP13512 extended-release dose provided extended gabapentin exposure (time to maximum concentration, 8.4 vs 2.7 hours) and superior bioavailability (74.5% vs 36.6%) .Toxicity: Gabapentin's most common side effects in adult patients include dizziness, fatigue, weight gain, drowsiness, and peripheral edema (swelling of extremities).

Specifications

仕様と純度

Moligand™, 10 mM in DMSO

保管条件

Protected from light,Argon charged,Store at -80°C

入荷

Dry ice packs + Cold packs

この製品は冷冷この冷このこの製品の運送が必要です。地上およびその他の経済サービスは利用できません。

等級

Moligand™

製品の性質

ALogP

3.1

名前と識別子

異性体SMILES

CC(C)C(=O)OC(C)OC(=O)NCC1(CCCCC1)CC(=O)O

分子量

329.39

Reaxy-Rn

10188772

Reaxys-RN_link_address

https://www.reaxys.com/reaxys/secured/hopinto.do?context=S&query=IDE.XRN=10188772&ln=

Application Protocols

No vendor-tested bioassay protocols are provided in the Product Data for this item.

General research-use protocol templates (non-binding guidance):

• Preparation of DMSO stock:
  • Dissolve compound to 10–50 mM in anhydrous DMSO under inert atmosphere. Aliquot into amber vials; store at -80°C. Avoid repeated freeze–thaw cycles.
• Enzymatic hydrolysis assay:
  • Incubate 1–10 µM compound with esterase/carboxylesterase in phosphate buffer (pH 7.4) at 37°C. Sample at defined intervals, quench with ice-cold ACN containing internal standard, and quantify parent/prodrug by LC-MS/MS.
• Permeability (PAMPA) screen:
  • Dose 10 µM from DMSO stocks into donor well (final DMSO ≤0.5%), incubate 4–6 h at 25–37°C, then measure acceptor concentration to estimate Pe. Analyze intact prodrug vs released parent.

These outlines are for experienced researchers; adapt conditions to your system, and validate using appropriate controls and analytical methods.

Biological Roles

General/literature context (no therapeutic claims):

• Prodrug design: Gabapentin enacarbil is engineered to transiently mask the polar amine and acid functionalities of gabapentin using cleavable carbamate/ester groups. This increases apparent lipophilicity and modulates ionization, facilitating membrane permeation and engagement with uptake pathways.

• Bioconversion: In biological systems, ubiquitous hydrolases (esterases, amidases/carboxylesterases) can sequentially cleave promoieties, ultimately regenerating gabapentin. The kinetics and site of activation depend on enzyme expression and local pH, with plasma and hepatic tissues commonly contributing to conversion (literature generality for acyloxyalkyl carbamates).

• Transport phenomena: The neutral/lipophilic character of the prodrug can improve passive diffusion and may interact with nutrient transport mechanisms relative to the parent amino acid analogue (general prodrug principle).

• Research utility:

  • Tool compound for dissecting the impact of prodrugging on permeability, transporter interactions, and PK surrogates in preclinical models.
  • Benchmark for comparing alternative promoieties (e.g., carbonate vs carbamate vs phosphonooxymethyl) in prodrug optimization.

Note: The above describes general biochemical behavior of ester/carbamate prodrugs and is provided for research design context only.

Buffer Applications

Not typically applicable. Gabapentin enacarbil is a drug-like small molecule and is not used as a buffering agent. For assay work, standard biological buffers (e.g., PBS, HEPES, Tris) can be used as diluents when introducing the compound from DMSO stocks. Ensure final cosolvent content is controlled and that buffer pH does not promote unwanted hydrolysis (avoid strong base).

Green Alternatives

While gabapentin enacarbil itself is a specific research prodrug (not readily substitutable), greener choices can be made in its handling and analysis.

• Solvent choices (general guidance):

  • Prefer aqueous buffers with minimal DMSO when feasible; target ≤0.1–0.5% DMSO in final assay media.
  • Ethanol or 2-propanol can sometimes replace DMF/ACN as cosolvents for intermediate steps, recognizing lower solvency and potential biological effects.

• Chromatography considerations:

  • Use water–ethanol or water–MeOH gradients instead of water–acetonitrile when compatible with detection and retention; MeOH is often considered a greener organic modifier than ACN.

• Stock and storage practices:

  • Prepare higher-concentration DMSO stocks in small aliquots to minimize waste and repeated freeze–thaw cycles.

• Tradeoffs:

  • Greener solvents may reduce solubility and assay consistency for lipophilic prodrugs; validate recovery and potency when modifying solvent systems.

Simple comparison (general):

• DMSO vs ethanol as stock solvent
  • Solvency: DMSO high; ethanol moderate
  • Biocompatibility at low %: both acceptable; ethanol evaporates faster
  • Environmental footprint: ethanol preferred; ensure sealed handling to control volatility

Pharmaceutical Uses

Research/formulation context only; no therapeutic claims.

• Role: Investigational and reference prodrug of gabapentin used in research to study absorption enhancement and prodrug activation. For laboratory/formulation studies, both free base and salt forms may be evaluated to optimize stability and handling.

• Formulation considerations (general/literature):

  • Salt selection can impact crystallinity, hygroscopicity, and dissolution rate; consult CoA for the exact form supplied for this SKU.
  • Solid-state stability is influenced by moisture and temperature; ester/carbamate prodrugs benefit from dry, low-temperature storage and light protection.
  • For preclinical dosing solutions, mixed solvents (e.g., PEG400/water, aqueous surfactants, or citrate/phosphate buffers with limited DMSO/ethanol) are commonly explored; confirm chemical stability over the intended dosing window by LC.

• Regulatory status: Not addressed here. This product is supplied strictly for research use only and not for human or veterinary administration.

• Documentation: For any GMP-adjacent exploratory work (e.g., method development), secure CoA/Spec Sheet detailing purity, identity, and form.

Physical Properties

Item-specific physical constants are not provided in the Product Data for this listing.

• Item-specific values:

  • Appearance: Not specified for this item; refer to CoA/Spec Sheet.
  • Melting point: Not specified for this item; refer to CoA/Spec Sheet.
  • Boiling point: Not applicable (decomposes before boiling under ambient pressure for most drug-like solids); specific value not specified for this item; refer to CoA/Spec Sheet.
  • Density/refractive index: Not specified for this item; refer to CoA/Spec Sheet.
  • Solubility (item-specific): Not specified for this item; refer to CoA/Spec Sheet.

• General/literature guidance (non-spec):

  • Physical state: typically an off-white to white solid for the free base or salt forms (literature).
  • Solubility profile: commonly formulated in polar aprotic solvents (DMSO) for screening stocks; limited aqueous solubility expected for the neutral prodrug relative to gabapentin (literature).
  • pKa/logP: Prodrug masking reduces apparent basicity/ionization and increases lipophilicity compared with gabapentin; exact values depend on salt/form and are literature-dependent.

• Practical handling note:

  • Prepare concentrated DMSO stocks (e.g., 10–50 mM) and dilute into assay buffers with attention to final DMSO content (≤0.1–0.5% v/v typical for biochemical assays). Verify solubility visually and by analytical QC (HPLC/UPLC).

Quality and Grades

• Supplied Grade: Moligand™.

  • Context: Moligand™ denotes suitability for ligand discovery, screening libraries, and medicinal chemistry hit validation. Typical expectations include high chemical purity by HPLC/UPLC, identity confirmed by spectroscopic methods, and low residual solvents/metals suitable for in vitro research. Exact acceptance criteria for this SKU are Not specified for this item; refer to CoA/Spec Sheet.

• What this means for users:

  • Intended for research use (biochemical, cellular, and ADME/transporter assay development), not for human or veterinary use.
  • QC emphasis is placed on structural identity and chromatographic purity to support SAR and screening reproducibility; UV background and stability are considered for plate-based assays.

• Stabilizers/additives: Not specified for this item; refer to CoA/Spec Sheet.

• Analytical documentation:

  • CoA/Spec Sheet provides lot-specific purity, identity (e.g., NMR, MS), and any stabilizer or counterion information. Request these documents if they are not included by default with your shipment.

• Practical notes:

  • For consistency across screens, document the exact form (free base vs salt) and hydrate/solvate state if applicable. Small differences can shift apparent potency in transporter or esterase assays. Verify with CoA.

Reaction and Applications

This compound is primarily used as a research-grade reference prodrug in discovery biology rather than as a synthetic reagent.

• Discovery and ADME applications (research use only):

  • Transporter studies: Evaluate uptake via nutrient transporters and prodrug activation by esterases and amidases (literature concept for acyloxyalkyl carbamate prodrugs).
  • Metabolic profiling: In vitro hydrolysis kinetics in plasma, S9 fractions, microsomes; identification of intermediate carbonate/ester cleavage products and release of gabapentin (general literature guidance).
  • Permeability assays: PAMPA/Caco-2/MDCK to quantify improvements relative to gabapentin (research context).

• Analytical applications:

  • Reference standard for LC-MS/MS method development (parent and deprotection fragments). Optimize source parameters to minimize in-source hydrolysis.
  • Stability-indicating HPLC methods under ICH-like stressors (acid/base hydrolysis, oxidative conditions, light) to map degradation pathways.

• Practical notes:

  • Prepare fresh working solutions; keep cold and protected from light to suppress non-enzymatic hydrolysis.
  • When comparing to gabapentin, normalize for free parent exposure in activation assays (measure both prodrug and released parent over time).

• Not commonly used in classical synthetic transformations (e.g., coupling, cross-coupling) beyond derivatization studies of prodrug linkers.

Reaction Conditions

General conditions for studying or manipulating ester/carbamate prodrugs (literature guidance; not item-specific specs):

• Hydrolysis (chemical):

  • Basic: Aqueous NaOH or K2CO3 (0.01–0.1 M) in MeOH/H2O or ACN/H2O at 20–37°C typically accelerates ester/carbamate cleavage. Monitor by LC; quench to neutral promptly to avoid over-degradation.
  • Acidic: Dilute HCl (0.01–0.1 M) in MeOH/H2O at ambient to 37°C promotes ester hydrolysis; carbamates may require longer times.

• Enzymatic activation:

  • Porcine liver esterase or human carboxylesterase preparations in phosphate buffer (pH ~7.4) at 37°C can model bioconversion. Include appropriate negative controls and time-course sampling.

• Stability testing:

  • pH 2, 7.4, and 9 buffers at 25–40°C to map degradation rates; protect from light and minimize oxygen exposure.

• Analytical:

  • LC-MS with soft ionization (reduced source temperature/fragmentor voltage) to limit in-source hydrolysis; use stability-indicating gradients with aqueous modifiers (0.1% FA or 10 mM ammonium formate).

Expected outcomes:

• Faster degradation under basic conditions; formation of intermediate carbonate fragments prior to release of the parent amine/acid (gabapentin). Always confirm structures by MS/MS and, where needed, NMR.

Safety and Handling

• GHS/CLP classification and hazard statements: Not specified for this item; refer to the SDS for authoritative hazard information.
• Signal word and pictograms: Not specified for this item; refer to SDS.

General laboratory safety guidance (non-spec, best practice):

• PPE: Use lab coat, safety glasses, and appropriate chemical-resistant gloves (e.g., nitrile). Handle powders in a fume hood or ventilated enclosure to minimize inhalation of particulates.
• Avoid generating dust; prevent exposure by inhalation, ingestion, or skin/eye contact. Wash thoroughly after handling.
• Incompatibilities: Avoid strong acids/bases and strong oxidizers which may promote hydrolysis or degradation of ester/carbamate functionalities. Moisture may accelerate hydrolysis; keep containers tightly closed under inert gas as specified.
• First aid (overview; defer to SDS): If inhaled, move to fresh air; if on skin or in eyes, rinse with water for at least 15 minutes; if ingested, rinse mouth and seek medical attention. Provide SDS to healthcare personnel.
• Fire safety: Treat as an organic combustible solid; use CO2, dry chemical, or foam. Combustion may produce COx/NOx.
• Waste: Dispose of contents/container according to institutional and local regulations. Avoid release to the environment.

Follow item-specific storage in this listing: protect from light, store under argon at -80°C; minimize freeze–thaw cycles.

Solvent Selection

Gabapentin enacarbil is a neutral/lipophilic prodrug relative to gabapentin, favoring polar aprotic solvents for stock preparation.

• Working stocks:

  • DMSO is the primary choice for screening stocks due to high solvating power and assay compatibility at low v/v.
  • Alternative organic cosolvents: DMF or ethanol can be used, followed by dilution into aqueous buffers with surfactant or protein carrier if needed.

• Aqueous handling:

  • Aqueous solubility is lower than gabapentin (literature generalization). For biochemical assays, introduce as DMSO microaliquots into buffered media, ensuring final DMSO ≤0.1–0.5%.
  • Use gentle warming (≤37°C) and brief sonication to aid dissolution; avoid prolonged heating to limit hydrolysis of ester/carbamate functions.

• Compatibility considerations:

  • Avoid strong basic aqueous conditions during stock preparation to prevent premature hydrolysis.
  • For LC-MS bioanalytical standards, 50:50 water:acetonitrile (0.1% formic acid) often balances solubility and chromatographic performance; confirm recovery empirically.

• Quick comparison (general):

  • DMSO: highest solvency, best for concentrated freezer stocks.
  • Ethanol: lower solvency, good for cell-based systems with tight DMSO limits; watch evaporation.
  • DMF: strong solvency but higher toxicity; reserve for chemistry workflows, not biology-facing assays.

Storage and Reconstitution

• Storage conditions (item-specific):

  • Protected from light.
  • Argon charged (store under inert gas).
  • Store at -80°C.
  • Shipped on dry ice packs + cold packs.

• Stability guidance:

  • Keep tightly closed in original container. Allow vials to equilibrate to room temperature in a desiccated environment before opening to avoid moisture condensation.
  • Minimize headspace oxygen and moisture; promptly re-purge with argon/nitrogen after use.

• Reconstitution (general best practice):

  • Prepare concentrated stocks in anhydrous DMSO (e.g., 10–50 mM). Vortex and, if needed, briefly sonicate. Filter through 0.2 µm PTFE syringe filter for assay-critical work.
  • For aqueous working solutions, dilute DMSO stocks into pre-chilled buffer with rapid mixing; keep final DMSO low and use immediately to limit hydrolysis.

• Aliquoting and freeze–thaw:

  • Dispense single-use aliquots to avoid repeated freeze–thaw cycles. Record preparation date and concentration on each aliquot.

• Expiry:

  • Item-specific retest/expiry period is Not specified for this item; refer to CoA/Spec Sheet. Reassess by HPLC/LC-MS after extended storage or if visual/analytical changes are observed.

• Research use note: For research use only.

Structure and Identity

Gabapentin enacarbil is a small-molecule prodrug of gabapentin, featuring masked polar groups to enhance permeability and transporter engagement.

• Item-specific identifiers from Product Data:

  • SKU: G1498489
  • CAS: 478296-72-9
  • Category: Small molecules and compound library (research use)
  • Grade: Moligand™
  • SMILES: Not specified for this item; refer to CoA/Spec Sheet.
  • InChIKey: Not specified for this item; refer to CoA/Spec Sheet.
  • Molecular formula: Not specified for this item; refer to CoA/Spec Sheet.
  • Molecular weight: Not specified for this item; refer to CoA/Spec Sheet.

• Structural features (general/literature description):

  • Prodrug of gabapentin constructed via an acyloxyalkyl carbamate/ester masking strategy.
  • Contains a carbamate linkage and ester promoieties that are hydrolytically labile, unveiling gabapentin under enzymatic or chemical conditions.
  • Aliphatic scaffold; no aromatic rings; multiple heteroatoms (O, N) distributed in carbamate/ester and amino acid–like core.
  • Designed to be more lipophilic and neutral at physiological pH relative to gabapentin, favoring uptake via transporters.

• 2D structural description (general):

  • Central substituted cycloalkyl–like backbone bearing a primary amine (masked in prodrug form) and a latent carboxylate.
  • One side bears a carbonate/ester chain; the other includes an additional ester function; both serve as cleavable promoieties to regenerate the parent amino acid after absorption.

Synthetic Utility

Gabapentin enacarbil is not commonly employed as a building block in synthetic chemistry campaigns; however, its functionality provides educational and limited derivatization opportunities in a research setting.

• Functional group profile (general):

  • Acyloxyalkyl carbamate and ester groups: susceptible to hydrolysis (acid/base or enzymatic), transesterification under mild basic/alcoholic conditions, and carbonate exchange reactions.
  • Latent amino acid: Prodrug unmasking yields gabapentin after sequential cleavage.

• Use cases in the lab:

  • Hydrolysis and stability mapping to understand prodrug linker liabilities and to generate reference metabolites for analytical methods.
  • Comparative studies of carbamate vs carbonate vs simple ester masking on permeability and stability.

• Retrosynthetic insights (didactic):

  • Construction via carbamate formation on the parent amine, followed by installation of an acyloxyalkyl carbonate/ester promoiety under mild conditions; protecting-group orchestration prevents premature intramolecular cyclization or hydrolysis (general literature strategy for amino acid–like prodrugs).

Note: If synthetic modification is intended, control moisture and base strength to avoid global deprotection, and verify integrity by LC-MS/NMR after each step.

Target Specificity

Not specified for this item; refer to CoA/Spec Sheet.

Note: This product is not an antibody or biological probe with defined antigen/epitope specificity. In pharmacology research, it is used as a small-molecule prodrug reference; any transporter/enzyme interactions studied should be defined in the user’s experimental design and are outside item-specific specifications.

よくある質問

What is Moligand??

Moligand? is one of Aladdin Scientific's premium product lines, formulated for high-purity applications across multiple workflows. Compared to standard grades in the same workflow, Moligand? products typically offer tighter specifications, more rigorous QC, and stronger lot-to-lot consistency.

How should this product be stored?

Store at ?80 °C, protected from light, under argon. It is supplied under an argon blanket; reseal under inert gas after each use.

How is this product shipped?

This product ships frozen with dry ice and cold packs. Unpack on arrival and transfer it to the storage condition stated above; handle dry ice with insulated gloves in a ventilated area.

What are the CAS number, molecular formula and molecular weight?

The CAS Number is 478296-72-9, the molecular formula is C16H27NO6, and the molecular weight is 329.39 g/mol.

What documentation is provided?

Available product documentation, including Certificates of Analysis (COA), Safety Data Sheets (SDS), and specification sheets, is shown in the product document area. Document availability and access follow the current site policy.