GSK343 - Moligand™, 10 mM in DMSO , CAS No.1346704-33-3

CAS: 1346704-33-3 Cat. No.: G1496360 Summenformel: C₃₁H₃₉N₇O₂ Molekulargewicht: 541.69 EG-Nummer: 806-050-7

GRADE & PURITY Moligand™, 10 mM in DMSO

Storage

Store at -80°C

Shipped In

Dry ice packs + Cold packs

Übersicht

GSK343 is a highly potent and selective EZH2 inhibitor with an IC 50 of 4 nM.

Specifications

Spezifikationen & Reinheit

Moligand™, 10 mM in DMSO

Storage

Store at -80°C

Verschickt in

Dry ice packs + Cold packs

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

Note

Moligand™

Namen und Kennungen

Isomere SMILES

CCCC1=C(C(=O)NC(=C1)C)CNC(=O)C2=C3C=NN(C3=CC(=C2)C4=CC(=NC=C4)N5CCN(CC5)C)C(C)C

WGK Deutschland

3

Molekulargewicht

541.69

Reaxy-Rn

21972486

Reaxys-RN_link_address

https://www.reaxys.com/reaxys/secured/hopinto.do?context=S&query=IDE.XRN=21972486&ln=

Application Protocols

No in-house tested application protocols are specified for this item. The following general procedures are provided as research-use guidance only.

Example 1: Preparation of DMSO stock and biochemical assay dosing

• Dissolve compound to 10 mM in anhydrous DMSO. Vortex until homogeneous.
• Prepare a serial dilution (e.g., 1:3 or 1:5) in DMSO to create a range of concentrations.
• Add to assay plates such that final DMSO is constant (commonly 0.1–1% v/v) across all wells.
• Incubate with EZH2 enzyme, SAM, and substrate peptide per kit/manufacturer instructions; read via HTRF/AlphaLISA/radiometric method.

Example 2: Cell-based treatment (pilot conditions)

• Prepare an intermediate DMSO stock (e.g., 1 mM). Dilute into pre-warmed culture medium to the desired final concentration, keeping DMSO ≤0.1–0.5% v/v per cell-line tolerance.
• Treat cells for 24–72 h. Harvest and assess H3K27me3 by Western blot/ELISA; include vehicle and orthogonal controls.

Quality controls

• Verify stock concentration by UV or quantitative NMR if needed.
• Include cytotoxicity/viability readouts to separate on-target epigenetic effects from general stress responses.

These protocols are illustrative; optimize parameters for your specific system.

Biological Roles

Biological context (literature; not item-specific claims):

• Target/pathway: GSK343 is widely used as a selective inhibitor of EZH2, the catalytic SET-domain subunit of the Polycomb Repressive Complex 2 (PRC2). EZH2 catalyzes methyl transfer from SAM to histone H3 lysine 27 (H3K27), establishing mono-, di-, and tri-methyl marks that contribute to facultative heterochromatin formation and transcriptional repression.
• Mechanism of action (probe context): SAM-competitive binding within the EZH2 active site, reducing H3K27 methylation levels in biochemical and cellular systems in a concentration-dependent manner.
• Selectivity considerations: Probe studies typically evaluate cross-reactivity with EZH1 and other lysine methyltransferases to confirm selectivity; counterscreening panels (e.g., G9a/GLP, SETD family) are commonly used in publication-quality characterization.
• Cellular utility: Employed to modulate epigenetic states transiently to study gene expression programs, chromatin accessibility, and feedback regulation within PRC2-dependent networks. Effects are reversible upon compound washout.
• Not endogenous: This is a synthetic small molecule with no physiological role; any observed biological effects reflect target engagement and off-target profiles under the tested conditions.

Research-use limitation: For research use only. Not for human or veterinary use.

Buffer Applications

Not a buffering agent. This product does not function as an acid/base buffer or electrophoresis buffer component.

Practical handling in buffer systems (assay context):

• Delivery: Prepare a DMSO stock and dilute into the desired assay buffer (e.g., HEPES or Tris-buffered systems) ensuring the final DMSO content is consistent across samples and controls.
• Precipitation control: Add compound last, with gentle mixing; confirm solubility visually and by a quick absorbance scan if possible. Keep final organic cosolvent low to minimize assay interference.
• Protein-containing buffers: Binding to serum proteins or assay proteins may reduce apparent free concentration; consider using BSA-free buffers for biochemical assays or determine free fraction empirically.

Green Alternatives

This product functions as a target-selective research probe, not a process solvent or commodity reagent. Green chemistry substitution at the molecule level is generally not applicable because its value derives from its specific target interactions.

Where green considerations can apply:

• Solvent choices for handling: Prefer greener or safer solvents for cleaning and formulation when compatible with your assays (e.g., minimize DMF; use ethanol or water-cosolvent systems if they do not compromise solubility or assay integrity). DMSO remains the practical standard for small-molecule bioassays.
• Scale: Use the minimal effective quantities. Microplate-based assays reduce solvent use and waste.
• Waste management: Segregate halogenated and non-halogenated organic waste streams; neutralize acidic/basic washes before disposal per institutional EHS.

Comparison (contextual):

• DMSO vs DMF for stock solutions: DMSO is generally preferred due to lower toxicity and better worker safety profile; DMF should be avoided if not necessary.

Bottom line: Green “alternatives” are best implemented at the level of assay design (miniaturization, solvent selection, waste minimization) rather than substituting the probe itself.

Pharmaceutical Uses

This product is supplied for research use only and is not approved for human or veterinary applications.

Relevant non-clinical/formulation contexts (general):

• Reference standard: Can serve as a reference inhibitor in bioanalytical method development (e.g., LC–MS/MS) and in potency assays for EZH2-focused discovery projects.
• Preformulation studies: Solubility profiling in common cosolvents (DMSO, ethanol, PEG400/water) and stability screening across pH may be performed by users to support in vitro assay reliability. No pharmacopeial monograph is known for this specific probe.
• Excipient compatibility (assay context): Assess compatibility with assay additives (Tween-20, Pluronics, BSA) to avoid nonspecific binding or aggregation that can confound readouts.

Compliance notes:

• Not manufactured under GMP; not intended as an API, excipient, or in vivo dosing agent for regulated studies without further qualification. Users conducting GLP studies should qualify the material per their internal QA procedures.

Physical Properties

Item-specific physicochemical specifications (this lot):

• Appearance: Not specified for this item; refer to CoA/Spec Sheet.
• Molecular weight (spec): Not specified for this item; refer to CoA/Spec Sheet.
• Molecular formula (spec): Not specified for this item; refer to CoA/Spec Sheet.
• Melting point, boiling point, density, refractive index, water/peroxide/metal limits, UV cutoff: Not specified for this item; refer to CoA/Spec Sheet.

General/literature physicochemical information (for planning only; not item specifications):

• Physical state: Typically isolated as a solid small molecule (literature for probe compounds of this class).
• Solubility: Commonly dissolved in anhydrous DMSO to prepare concentrated stocks (e.g., 10–50 mM); aqueous solubility is usually limited without cosolvent or surfactant (literature, qualitative).
• Lipophilicity/ionization: Designed to be cell-permeable; overall neutral at physiological pH with multiple heteroatoms for target engagement (literature, qualitative). Exact logP/pKa not provided here.

Notes for users:

• If exact physicochemical constants are needed for formulation, stability modeling, or LC method development, consult the product CoA/Spec Sheet or measure empirically under your assay conditions.

Quality and Grades

• Grade: Moligand™

Interpretation of Moligand™ grade (Aladdin Scientific context):

• Intended use: Research-use-only small-molecule ligand/chemical probe quality, suitable for biochemical screening, target validation, and cell-based assay development.
• Emphasis: Identity and purity appropriate for discovery workflows. Not produced under GMP; not for diagnostic, therapeutic, or clinical use.
• Documentation: For lot-specific identity tests (e.g., HPLC/UPLC purity, HRMS, NMR) and any stabilizers or residual solvents, consult the CoA/Spec Sheet.

What is and is not specified for this catalog item:

• Purity threshold, stabilizers, residual solvent limits, and spectral data: Not specified for this item; refer to CoA/Spec Sheet.
• Appearance: Not specified for this item; refer to CoA/Spec Sheet.

Practical notes for users:

• For screening libraries or SAR campaigns, Moligand™-grade materials are typically suitable as reference standards or tool compounds. If ultra-low UV background or trace-metal specifications are required for specialized analytics, verify on the CoA or request additional documentation.
• If using in biophysical assays (e.g., ITC, SPR), consider additional user-side polishing (optional recrystallization or preparative HPLC) only if your assay sensitivity demands it; retain material for orthogonal verification (LC–MS, 1H NMR).

Reaction and Applications

This compound is primarily a bioactive chemical probe rather than a synthetic reagent. Consequently, it is not typically employed as a reagent, catalyst, or building block in standard organic reactions.

Research applications (literature/practice):

• Target class: EZH2 (the catalytic subunit of PRC2), a histone H3K27 methyltransferase.
• Use cases: Biochemical enzyme inhibition assays (IC50 determination), cellular target engagement, mechanistic studies of PRC2 function, epigenetic pathway interrogation, and as a reference control in assay development.
• Assay modalities: AlphaLISA/HTRF methyltransferase assays, radiometric SAM-dependent assays, TR-FRET, enzyme kinetics (competitive vs SAM), and cell-based readouts of H3K27me3 levels by Western blot or ELISA.

Practical assay tips:

• Pre-dilute concentrated DMSO stocks into assay buffer to minimize precipitation; ensure consistent final DMSO across wells.
• For kinetic characterization, vary both inhibitor and SAM concentrations to confirm competitive mechanism and derive Ki using appropriate models (e.g., global fit to competitive inhibition).
• Include counterscreens against related methyltransferases (e.g., EZH1, G9a) to verify selectivity in your system.

Note: If a synthetic transformation using this molecule is intended (e.g., for derivatization or PROTAC linkerization), treat it as an advanced intermediate—optimize protecting group and coupling strategies empirically.

Reaction Conditions

Not typically applicable. This compound is not used as a reagent or catalyst in synthetic transformations, so standardized “reaction conditions” do not apply.

Assay-condition guidance (research use; literature/practice):

• Stock preparation: Dissolve in anhydrous DMSO to prepare a concentrated stock (e.g., 10 mM). Vortex and, if necessary, sonicate briefly. Filter through 0.22 μm PTFE if particulate is observed.
• Biochemical assays: Titrate across a suitable concentration range bracketing the expected IC50. Maintain constant SAM and substrate peptide concentrations per your assay design; include DMSO-matched vehicle controls.
• Cellular assays: Typical working concentrations span low nanomolar to micromolar, determined empirically. Validate effects by measuring H3K27me3 levels and cell viability in parallel.
• Stability: Minimize freeze–thaw cycles of DMSO stocks; aliquot at first use. Protect from prolonged exposure to light and ambient moisture.

All values above are general literature/practice guidance only and are not specifications for this item.

Safety and Handling

Authoritative safety information must be taken from the SDS. The following guidance is general and non-exhaustive.

Item-specific hazard data:

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

General handling for research small-molecule probes:

• PPE: Wear lab coat, nitrile gloves, and safety glasses. Work in a fume hood to avoid inhalation of dust or aerosols.
• Avoid exposure: Prevent skin/eye contact and ingestion. Avoid generating dust. Use clean, dry tools to weigh.
• Storage incompatibilities: Keep away from strong oxidizers and moisture; avoid prolonged exposure to light and repeated freeze–thaw where degradation is possible (general guidance).
• First aid (overview): If skin contact occurs, wash with soap and water. If eye contact, rinse with water for several minutes and seek medical advice. If inhaled, move to fresh air. If ingested, rinse mouth and seek medical attention. Always follow your institution’s EHS protocols.
• Waste: Dispose according to local regulations for organic laboratory chemicals; do not release to the environment.

Special risks (general):

• No specific reactivity hazards are commonly reported for this class beyond typical organic compound risks; however, unknown toxicological properties warrant prudent handling on the milligram scale.
• Defer to the SDS for detailed spill response, incompatibilities, and transport classifications.

Solvent Selection

GSK343 is a hydrophobic, heteroatom-containing small molecule typically handled as a DMSO stock for biochemical and cell-based assays.

• Primary solvent (practice): Anhydrous DMSO is commonly used to prepare concentrated stocks (e.g., 10 mM) for accurate dosing in enzymatic or cellular assays (literature/practice; not an item specification).
• Aqueous systems: Direct water solubility is usually limited. For aqueous delivery, dilute DMSO stocks into buffered media ensuring final DMSO is within the assay’s tolerated range (often 0.1–0.5% v/v for sensitive cells; follow your internal SOPs).
• Alternative organic solvents: DMF or ethanol may solubilize in certain contexts; compatibility with the biological system must be confirmed experimentally.
• Cosolvents/surfactants: For challenging formulations, consider minimal amounts of non-ionic surfactants (e.g., Pluronic F-127) or cyclodextrin inclusion complexes; verify no interference with readouts.

Comparison pointers (general):

• DMSO vs DMF: DMSO is preferred for bioassays due to lower volatility and better biocompatibility at low percentages; DMF may have higher cytotoxicity.
• DMSO vs ethanol: Ethanol can be suitable for biochemical assays but is often less favored for cell assays due to membrane effects at similar v/v.

Quality control of stocks:

• Filter sterilize if needed for cell culture (0.22 μm PTFE for organic stocks). Record exact concentration and date; use amber vials to limit photodegradation if applicable.

Storage and Reconstitution

Storage conditions (item-specific):

• Storage temperature: Store at -80°C (as provided in Product Data).
• Shipped in: Dry ice packs + Cold packs (as provided in Product Data).

General handling and reconstitution (guidance; not item specifications):

• Upon receipt: Keep frozen. Allow the sealed container to equilibrate to room temperature before opening to prevent moisture condensation.
• Aliquoting: If supplied as a solid, promptly aliquot after first opening in a dry environment. If supplied in solution, subdivide into single-use aliquots to avoid freeze–thaw cycles.
• Solubilization: Prepare concentrated stocks in anhydrous DMSO (e.g., 10 mM). Vortex/sonicate briefly if needed until fully dissolved. Record concentration and preparation date.
• Storage of stocks: Store DMSO stocks at -20 to -80°C in amber vials. Minimize light exposure and freeze–thaw; discard if precipitation, discoloration, or potency loss is observed.
• Working solutions: Prepare fresh just before use by diluting DMSO stocks into assay buffer or cell culture medium. Maintain consistent final DMSO across samples.

Research use note: For research use only. Consult the CoA/Spec Sheet and SDS for authoritative guidance on stability limits, retest dates, and safe handling.

Structure and Identity

Overview: GSK343 is a well-known small-molecule chemical probe classified as a selective, SAM-competitive inhibitor of the histone methyltransferase EZH2 (component of PRC2) used in epigenetics research.

• SKU: G1496360
• Product name: GSK343
• CAS: 1346704-33-3 (literature-verified identifier for GSK343)
• PubChem CID: 71268957 (literature)
• 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 (general, literature):

• Functional role: Designed to occupy the S-adenosyl-L-methionine (SAM) binding pocket of EZH2, acting as a competitive inhibitor of methyl transfer to H3K27.
• Typical scaffold characteristics: Drug-like, heteroaromatic inhibitor framework optimized for EZH2; non-peptidic, contains multiple hydrogen-bond acceptors/donors arranged to mimic SAM-pocket interactions.
• Stereochemistry: Reported as an achiral small molecule in common probe form (literature). No stereochemical centers typically cited.

2D structure in words (literature, qualitative):

• A compact poly-heteroaromatic core bearing substituents that project into the SAM pocket and adjacent subpockets of EZH2, with polar functionalities enabling key H-bonds and hydrophobic elements improving affinity and selectivity.

Synthetic Utility

This molecule is intended as a finished probe for biochemical use rather than a synthetic building block. It lacks widely used functional handles for routine cross-coupling or protection–deprotection sequences in standard synthesis campaigns.

That said, for medicinal chemistry or chemical biology derivatization (general guidance):

• Probe derivatization: Researchers sometimes introduce linkers for PROTAC development, activity-based probes, or immobilization on affinity matrices. Site selection requires structure–activity relationship (SAR) knowledge to avoid disrupting EZH2 binding.
• Isosteric replacement: Modifications around heteroaromatic motifs or peripheral substituents may tune potency/selectivity. Parallel synthesis and mini-SAR exploration can be guided by docking or co-crystal structures (if available in literature for EZH2–probe complexes).
• Analytical characterization: Any semisynthetic derivatives should be confirmed by HRMS and NMR; for binding retention, re-profile against EZH2 and key off-target methyltransferases.

Caveat: No standardized coupling sites are specified for this catalog item; derivatization strategies should be planned based on primary literature precedent for GSK343 or close analogs.

Target Specificity

Item-specific validated target data (catalog testing): Not specified for this item; refer to CoA/Spec Sheet and any available technical notes.

General literature information (for context only):

• Primary target class: EZH2 histone methyltransferase (PRC2 catalytic subunit).
• Mechanism: SAM-competitive inhibition within the SET domain active site.
• Selectivity: Published characterizations typically include selectivity over EZH1 and a panel of lysine methyltransferases; users should confirm selectivity in their assay system with appropriate counterscreens.

Note: The above target context is for background understanding and should not be construed as a performance guarantee for this specific lot.