γ-Secretase modulator 4 - Moligand™, 10 mM in DMSO , CAS No.1420200-82-3

CAS: 1420200-82-3 Cat. No.: S1495894 Summenformel: C₂₃H₁₉FN₄O₂ Molekulargewicht: 402.42

GRADE & PURITY Moligand™, 10 mM in DMSO

Storage

Store at -80°C

Shipped In

Dry ice packs + Cold packs

Übersicht

γ-Secretase modulator 4 is a potent γ-secretase modulator, reduces the Aβ42 level with IC 50 s of 0.014 μM and 0.017 μM in human and mouse, respectively.

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

• Molekulargewicht: 402.42

Application Protocols

Item‑specific, tested application protocols and recommended dilutions are not provided for this product. Refer to the CoA/Spec Sheet and relevant publications for protocols specific to γ‑secretase modulators.

General guidance (not a specification)

• Prepare a concentrated DMSO stock under dry conditions; aliquot and store frozen. Thaw once, dilute into assay buffer/culture media with vigorous mixing to avoid localized precipitation. Maintain constant vehicle percentage across all wells/samples.
• For cell assays: Begin with a 10‑point half‑log dilution series bracketing anticipated potency; include cytotoxicity controls and vehicle controls. Verify compound stability over the assay window.
• For biochemical assays: Optimize detergent composition and lipid environment to support γ‑secretase activity; quantify peptide products by ELISA or LC‑MS.

These are general starting points and must be adapted and validated for your laboratory system.

Biological Roles

General background (literature; not a medical claim)

• γ‑Secretase is a multi‑subunit intramembrane aspartyl protease complex (presenilin, nicastrin, APH‑1, PEN‑2) responsible for regulated intramembrane proteolysis of numerous type‑I membrane proteins, including APP and Notch. Its activity generates peptides of varying lengths depending on processivity.

Role of γ‑secretase modulators (GSMs)

• GSMs are small molecules that allosterically modulate the processivity of γ‑secretase, often redistributing Aβ product profiles (e.g., lowering longer Aβ species while increasing shorter ones) without fully blocking cleavage. This distinguishes them from γ‑secretase inhibitors (GSIs), which broadly suppress activity and can impact Notch signaling.
• GSMs are valuable research tools to dissect stepwise ε‑, ζ‑, and γ‑cleavages, to study substrate selectivity, and to probe the conformational dynamics of the presenilin catalytic core.

Experimental readouts (guidance)

• Quantify Aβ peptides via ELISA, MSD, or LC‑MS; monitor Notch intracellular domain (NICD) formation to assess sparing of Notch processing. Use time‑course and concentration–response experiments to characterize modulation profiles.

Caveats

• GSM effects can be substrate- and cell‑context dependent. Protein/lipid composition of membranes, endosomal pH, and compound accumulation may influence observed outcomes. Always include matched vehicle controls and, where possible, benchmark GSM references.

Note: Specific binding constants, potency, and selectivity for this item are not provided here; consult the CoA/Spec Sheet or primary literature if available.

Buffer Applications

This product is a bioactive small molecule rather than a buffering agent, so it is not used to establish buffer pH.

Practical assay buffer considerations (general guidance)

• Common assay buffers: HEPES or PBS at physiological ionic strength (e.g., 10–50 mM HEPES, 150 mM NaCl, pH 7.2–7.5) for cell‑based or biochemical γ‑secretase assays.
• Organic co‑solvent: Keep DMSO at the lowest effective percentage (often ≤0.1–0.5% v/v final) to maintain solubility while minimizing assay interference.
• Additives: 0.01–0.05% non‑ionic surfactant (e.g., Tween‑20) can help prevent adsorption and precipitation; 0.1% BSA may reduce nonspecific binding in some formats.
• Filtration: For biochemical assays, 0.22 µm filtration of buffers reduces particulate background; avoid adsorptive membranes for hydrophobic ligands.

Item‑specific buffer properties, pKa, and pH ranges are not applicable and are not specified for this item.

Green Alternatives

As a bioactive small molecule rather than a bulk solvent or reagent, “green alternatives” center on choosing greener handling solvents and practices.

• Preferred solvent systems (general guidance)

  • Aqueous buffers with minimal DMSO (≤0.1–1% v/v) are favored in assays to reduce organic burden. Where possible, replace DMF/NMP with DMSO or EtOH for intermediate dilutions.

• Solvent comparison (general, literature)

  • DMSO: High solvency, fully miscible with water; comparatively low volatility and flammability—often preferable to DMF/NMP from a worker‑exposure and environmental standpoint.
  • EtOH: Renewable feedstock, low toxicity; limited ability to solubilize very hydrophobic ligands.
  • DMF/NMP: Strong solvency but reproductive toxicity concerns; avoid if feasible.

• Practice improvements

  • Use high‑concentration stocks to minimize total solvent usage; perform precise micro‑dosing (acoustic/positive‑displacement) to reduce waste.
  • Employ closed‑well plate formats and lids/seals to limit evaporative emissions and cross‑contamination.
  • Consolidate and segregate organic waste streams (DMSO‑rich vs alcohol‑rich) to facilitate appropriate disposal.

These recommendations are general and not item‑specific specifications.

Pharmaceutical Uses

• This product is supplied strictly for research use only. It is not formulated as a pharmaceutical, API, or excipient, and there is no pharmacopeial monograph associated with this SKU.

Research/manufacturing context (general)

• Potential roles include use as a reference material or control ligand in discovery workflows (biochemical assays, cell‑based assays, and analytical method development related to γ‑secretase biology).
• For any preclinical formulation work (in vitro), typical vehicles may include DMSO stocks subsequently diluted into aqueous buffers or, for in vivo method development (not supplied/approved for such use), specialized vehicles are often required; such applications fall outside the scope of this catalog item.

Item‑specific regulatory status, residual solvent profile, and stability‑indicating methods: Not specified for this item; refer to CoA/Spec Sheet.

Physical Properties

Item-specific physicochemical properties

• 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 specified for this item; refer to CoA/Spec Sheet.
• Density: Not specified for this item; refer to CoA/Spec Sheet.
• Refractive index: Not applicable to solids; if liquid, not specified for this item; refer to CoA/Spec Sheet.
• Solubility: Not specified for this item; refer to CoA/Spec Sheet.
• LogP/logD: Not specified for this item; refer to CoA/Spec Sheet.
• pKa: Not specified for this item; refer to CoA/Spec Sheet.

General considerations (literature/guidance, not item-specific)

• Many GSMs are hydrophobic and are commonly handled as concentrated DMSO stock solutions (e.g., 10–50 mM) for screening applications; aqueous solubility can be low without co-solvent. This is general guidance only and not a specification for this product.
• For aqueous work, co‑solvents (DMSO ≤1–2% v/v in final assay buffers) and surfactants (e.g., 0.01–0.05% Tween‑20) are frequently used in discovery workflows to maintain homogeneity; compatibility must be verified experimentally for your system.

Quality and Grades

• Grade/Purity: Moligand™ (item-specific)
  • This denotes a discovery‑grade, screening‑quality small molecule suitable for in vitro biochemical and cell‑based research applications. The emphasis is on ligand utility in target modulation and library/assay compatibility.

What this means in practice (general guidance)

• Suitability: Intended for research use only (not for human or veterinary use). Typically appropriate for target validation, phenotypic screening, and mechanism studies.
• Documentation: For exact purity, identity confirmation (NMR/LC‑MS/HPLC), and any stabilizers or counter‑ions, refer to the item’s CoA/Spec Sheet. Do not assume pharmacopeial compliance.
• UV/LC performance: When used in LC‑based assays, verify baseline characteristics (UV absorbance, LC‑MS ionization) empirically; no low‑UV “HPLC grade” solvent claims apply to this solid compound.

Item‑specific clarifications

• Purity percentage, residual solvents, water content, or salt form: Not specified for this item; refer to CoA/Spec Sheet.
• Stabilizers/inhibitors: Not specified for this item; refer to CoA/Spec Sheet.

Reaction and Applications

Primary use case

• This product is positioned as a small‑molecule γ‑secretase modulator for research use. Its principal applications are in biochemical and cell‑based assays interrogating γ‑secretase activity and product profiles.

Typical research applications (general; not item‑specific claims)

• Mechanistic studies: Evaluate modulation of APP processing by γ‑secretase and quantify shifts in Aβ peptide length distributions (e.g., Aβ42, Aβ40) via ELISA or LC‑MS.
• Target engagement: Use CETSA/thermal shift or photoaffinity/competition approaches (if derivatives are available) to probe binding to the γ‑secretase complex or associated subunits.
• Phenotypic screening: Assess downstream pathway readouts impacted by altered intramembrane proteolysis in relevant cell models expressing APP/Notch reporters.
• Selectivity profiling: Compare effects on APP versus Notch processing using dual‑substrate assays to distinguish modulators from pan inhibitors.

Practical tips (general guidance)

• Prepare concentrated DMSO stocks under dry conditions; aliquot to avoid freeze–thaw. Verify absence of precipitation upon dilution into aqueous buffers (target ≤0.1–0.5% DMSO v/v final, as assay allows).
• Include vehicle controls matched for DMSO content. Conduct serial dilutions to generate full concentration–response curves (e.g., 8–12 points, 0.3–1/2‑log spacing).
• Confirm activity with orthogonal assays (biochemical vs. cellular) to deconvolute uptake and metabolism effects.

Note: No synthetic reaction applications are claimed for this item; it serves as a biological research ligand/modulator.

Reaction Conditions

Chemical reaction conditions are not applicable: this product is not sold as a preparative reagent or catalyst.

Assay‑oriented conditions (general guidance; not item‑specific specifications)

• Stock preparation: Often prepared at 10–50 mM in anhydrous DMSO, stored at −20 to −80 °C in aliquots to avoid freeze–thaw. Actual solubility for this item is not specified; confirm empirically.
• Working concentrations: Typical screening ranges span low nM to low tens of µM; construct full concentration–response curves to determine apparent potency/efficacy in your system.
• DMSO tolerance: Keep final DMSO ≤0.1–1% v/v depending on cell line/assay compatibility.
• Incubation: 1–24 h in cellular assays; 30–120 min in biochemical assays are common starting points; optimize per protocol.

Note: These are literature‑style guidelines for GSMs generally. No item‑specific potency, kinetics, or stability data are provided here.

Safety and Handling

GHS and hazard information (item-specific)

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

General laboratory precautions (guidance; consult SDS for authoritative instructions)

• Personal protective equipment: lab coat, safety glasses, and appropriate chemically resistant gloves (e.g., nitrile). Handle in a fume hood to avoid inhalation of dust/aerosols.
• Avoid exposure routes: inhalation, ingestion, skin/eye contact. Wash thoroughly after handling.
• Incompatibilities: Strong oxidizers and strong acids/bases may be incompatible with many organic small molecules; segregate until specific compatibility data are confirmed.
• Thermal sensitivity: Store frozen as specified to minimize degradation; avoid repeated freeze–thaw.
• First aid (overview): In case of skin/eye contact, rinse with plenty of water and seek medical attention if irritation persists. If inhaled, move to fresh air. If swallowed, rinse mouth and seek medical advice. Follow institutional SOPs.

Waste and spill response

• Collect small organic‑compound spills with inert absorbent; dispose according to local regulations. Prevent discharge to drains. Always prioritize the SDS for product‑specific measures.

Solvent Selection

Because the detailed structure is not disclosed here, select solvents using general best practices for lipophilic discovery compounds.

• Primary stock solvent (common practice; literature):
  • DMSO: Widely used for small‑molecule screening stocks due to broad solvating power, miscibility with water, and compatibility with most biochemical and cell assays at ≤0.1–1% v/v final concentration. Filter sterilize if required (PTFE or PES).
• Secondary/co‑solvents for method development (guidance):
  • DMF, NMP: Strong polar aprotic options for analytical sample prep; assess cytotoxicity if used in biological systems.
  • EtOH or MeOH: Useful for analytical standards; limit to low % in biological assays.
  • Aqueous buffers: Often require a co‑solvent (e.g., DMSO) and gentle heating/sonication to fully dissolve hydrophobic ligands.
• Solubility enhancement strategies (general):
  • Warm (≤37 °C) sonication, serial dilution from a concentrated DMSO stock, inclusion of non‑ionic surfactants (e.g., 0.01–0.05% Tween‑20) or carrier proteins (e.g., 0.1% BSA) where compatible.
• Quick comparison (general)
  • DMSO: Highest solvency; biologically compatible at low %; hygroscopic.
  • EtOH: Volatile, easier to remove; lower solvency for highly lipophilic chemotypes.
  • DMF/NMP: Strong solvency; potential assay interference—validate carefully.

Always verify actual solubility and assay compatibility experimentally for this specific SKU.

Storage and Reconstitution

Item‑specific storage and shipping

• Storage conditions: Store at −80 °C (as provided in Product Data). Minimize freeze–thaw cycles; keep container tightly closed under inert, dry conditions if feasible.
• Shipped in: Dry ice packs + Cold packs (as provided in Product Data).

Reconstitution (general guidance; not item‑specific specifications)

• Solvent: DMSO is commonly used to prepare concentrated stocks of hydrophobic small molecules. If water solubility is required, first dissolve in DMSO, then dilute into buffer with thorough mixing.
• Concentration: Many discovery compounds are prepared at 10–50 mM in DMSO; actual solubility for this item is not specified and should be confirmed empirically.
• Handling: Warm gently to room temperature before opening to avoid moisture condensation. If precipitation occurs upon dilution, increase mixing time, adjust solvent ratio, or reduce target concentration.
• Aliquots: Prepare single‑use aliquots to avoid freeze–thaw; store aliquots at −80 °C and protect from light if the compound is light‑sensitive (not specified for this item).

Always consult the CoA/Spec Sheet and SDS for definitive, item‑specific instructions.

Structure and Identity

• SKU: S1495894
• Product name: γ-Secretase modulator 4
• CAS: 1420200-82-3
• CID: Not specified for this item; refer to CoA/Spec Sheet.
• InChIKey: Not specified for this item; refer to CoA/Spec Sheet.
• SMILES: 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

• Item-specific structure: Not specified for this item; refer to CoA/Spec Sheet.
• General class (literature): γ-Secretase modulators (GSMs) are small molecules that interact allosterically with the intramembrane γ-secretase complex. Many reported GSM chemotypes are lipophilic, often featuring aromatic/heteroaromatic rings and amide/urea/acid motifs; exact functional groups for this SKU are not provided here.

2D structure (description)

• Not provided for this item. In absence of a disclosed structure, no ring systems, substituent patterns, or stereochemistry are asserted. Please consult the product’s CoA/Spec Sheet for definitive identity data.

Synthetic Utility

This SKU is offered as a finished small‑molecule modulator for biological research rather than as a synthetic building block.

• Not typically used as a reagent, coupling partner, or intermediate in routine organic synthesis.
• If derivatization is desired for probe development (e.g., biotinylation, photoaffinity tags, fluorophore conjugation), such work requires knowledge of the specific structure and functional handles, which are not provided here. Refer to the CoA/Spec Sheet and primary literature for suitable vector sites and stability considerations.
• No named reactions or cross‑couplings are recommended for this item without structural disclosure; therefore, no synthetic protocols are proposed.

Target Specificity

Only item‑specific information may be listed here.

• Declared target: γ‑secretase (modulator) — from product name/classification.
• Detailed target attributes (binding site, Ki/IC50, selectivity vs. Notch or other substrates, species cross‑reactivity, off‑targets): Not specified for this item; refer to CoA/Spec Sheet or primary literature corresponding to CAS 1420200-82-3.

No antibody/biologic attributes (clone, isotype, antigen) apply to this small‑molecule product.