BACE1-IN-4 , CAS No.2361157-92-6

CAS: 2361157-92-6 Cat. No.: B1445268 분자식: C₂₁H₂₃F₂N₅O₄S₂ 분자량: 511.57

Storage

Store at -20°C

Shipped In

Ice chest + Ice pads

개요

BACE1-IN-4 is a potent and highly selective BACE1 inhibitor, with an IC 50 of 3.8 nM and a K i of 1.9 nM, more selective at BACE1 over BACE2. Anti-Alzheimer’s disease.

Specifications

보관 조건

Store at -20°C

배송

Ice chest + Ice pads

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작업 유형

INHIBITOR

이름과 식별자

분자량

511.57

Application Protocols

The following outlines general, non-item-specific procedures commonly used for small-molecule BACE1 inhibitors. Adjust based on your enzyme source and detection method.

A. Preparation of stock solutions (general)

• Dissolve BACE1-IN-4 in anhydrous DMSO to 10–50 mM. Sonicate briefly or warm gently (≤40°C) if needed. Filter through 0.22 µm PTFE if particulates persist. Store aliquots at −20°C, protected from moisture and light.

B. Biochemical BACE1 inhibition assay (fluorogenic substrate; general)

• Buffer: 50 mM sodium acetate, pH 4.5; 0.1 M NaCl; 0.01–0.05% CHAPS (optimize per enzyme source).
• Enzyme: Recombinant human BACE1, concentration adjusted to provide linear initial rates over the assay window.
• Substrate: APP-derived fluorogenic peptide near Km.
• Procedure: Preincubate enzyme with inhibitor (serially diluted; constant DMSO, typically 0.5–1.0% v/v) for 15–30 min at 25–37°C. Initiate with substrate. Monitor fluorescence continuously; calculate initial velocities and fit concentration–response to obtain IC50.

C. Cell-based assay (general)

• Prepare a 1000× DMSO stock and dilute into culture medium to a final DMSO ≤0.1–0.2%, as tolerated by the cells. Include vehicle controls and cytotoxicity counterscreens (e.g., ATP content assays) to distinguish enzyme inhibition from nonspecific effects.

Note

• No item-specific potencies, assay-validated concentrations, or solvent limits are provided in this listing; determine empirically and consult the SDS for safe handling.

Biological Roles

Biochemical context (general; no therapeutic claims)

• BACE1 (beta-site APP cleaving enzyme 1) is a membrane-associated aspartyl protease that catalyzes the rate-limiting cleavage of amyloid precursor protein (APP) at the beta site, initiating a proteolytic cascade yielding APP C-terminal fragments. Modulating BACE1 activity is therefore a key handle for dissecting APP processing pathways.

Role of BACE1 inhibitors as research tools

• Small-molecule BACE1 inhibitors, such as BACE1-IN-4, are used to transiently reduce BACE1 catalytic activity in vitro or in cell systems. This allows mapping of substrate processing, evaluating compensatory pathways (e.g., alpha-secretase), and establishing assay windows in screening platforms.
• In chemical biology, inhibitors support target validation methods (e.g., cellular thermal shift assays for engagement), and can be benchmarked against genetic perturbations (siRNA/CRISPR) to compare acute pharmacological versus chronic genetic effects.

Selectivity considerations

• Off-target activity on related aspartyl proteases (e.g., BACE2, cathepsin D) can confound interpretation. Counterscreens and proteomic panels are recommended to delineate specificity in your system.

Assay design implications

• Enzyme kinetics can be affected by buffer pH (BACE1 typically exhibits acidic pH optima in vitro), ionic strength, and detergents that mimic membrane environments. Consistent DMSO content across controls and test wells is essential to avoid artifactual shifts in activity.

Item-specific potency/targets: Not specified for this item; consult the CoA/Spec Sheet and your in-house assay data.

Buffer Applications

While this product is not a buffer reagent, appropriate buffer systems are critical for BACE1 enzymology and inhibitor testing.

General buffer guidance for BACE1 assays (literature/general)

• pH: BACE1 exhibits optimal activity in acidic conditions; many assays employ buffers in the pH 4.0–5.5 range. Citrate–phosphate, sodium acetate, or MES are common choices. Validate pH against your substrate and detection method.
• Ionic strength: 100–200 mM total ionic strength is typical; adjust NaCl to stabilize the enzyme without suppressing activity.
• Detergents: Low concentrations (e.g., 0.01–0.1% CHAPS, Triton X-100, or Tween-20) may be used to mimic membrane environments and reduce nonspecific adsorption; verify compatibility with detection modality.
• Reducing agents/chelators: Additives such as DTT (0.5–2 mM) or EDTA (0.5–2 mM) can stabilize preparations, but confirm they do not interfere with catalysis or readout.

DMSO handling

• Maintain a constant final DMSO percentage across wells (commonly 0.1–1.0%) to avoid solvent-driven activity shifts. Prepare inhibitor stocks at high concentration (e.g., 10–50 mM) to minimize carryover.

Practical notes

• Filter or centrifuge buffers to remove particulates; pre-equilibrate to assay temperature.
• Include vehicle controls, no-enzyme controls, and known inhibitor controls where available. For this item, no validated control concentration is specified; determine empirically.

Green Alternatives

Context

• As a solid small-molecule inhibitor used in very small quantities for bioassays, the primary “green chemistry” considerations center on solvent choice for stock solutions, waste minimization, and avoiding halogenated solvents during analytical workups.

Greener solvent choices (general guidance)

• Preferred: Water (when feasible), aqueous buffers, and DMSO (biorenewable content is limited but it is low volatility, low flammability, and broadly accepted for bioassays).
• Alternatives to reduce hazardous waste: Replace DMF or chlorinated solvents in sample prep with ethanol or isopropanol when compatible with solubility and assay performance.

Comparison (general)

• DMSO vs DMF: DMSO offers lower toxicity/volatility and broad solvency; DMF may solubilize highly polar/poorly soluble compounds but has more stringent handling/waste requirements.
• Ethanol vs Methanol: Ethanol is typically preferred on safety and environmental grounds, provided the assay tolerates it.

Operational best practices

• Prepare concentrated stocks to minimize solvent volumes in the assay (aim for ≤1% v/v final DMSO/EtOH).
• Employ microscale assay formats (384/1536-well) to reduce reagent and solvent usage.
• Consolidate solvent waste streams and segregate halogenated from non-halogenated waste to enable appropriate disposal/recycling.

Note

• No item-specific stabilizers or green certifications are specified for this product; consult institutional green chemistry guidelines for implementation details.

Pharmaceutical Uses

This product is supplied strictly for research use only and is not intended for human or veterinary use, diagnostic procedures, or as a drug substance/excipient.

Formulation/excipient context

• No pharmacopeial status, excipient role, or manufacturing specification is provided for this item. It is not presented as a GMP-grade material.

Relevance to pharmaceutical research (general; no medical claims)

• In preclinical discovery laboratories, small-molecule inhibitors of proteases are used as tool compounds to benchmark assay performance, to explore structure–activity relationships (SAR), and to develop analytical methods (e.g., LC–MS bioanalytical assays). Such activities remain strictly non-clinical.

Documentation

• For any work intersecting regulated environments, obtain full characterization and purity data from the lot-specific CoA. If higher compliance is required (GLP/GMP), contact your QA group; this catalog item is not specified to meet those standards.

Conclusion

• No pharmaceutical or clinical application details are specified for BACE1-IN-4 in this listing. Use is limited to laboratory research under appropriate institutional approvals.

Physical Properties

Item-specific physical data

• 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 (typically a non-volatile solid for this class); item-specific value not specified.
• Density: Not specified for this item; refer to CoA/Spec Sheet.
• Refractive index: Not applicable for solids; item-specific value not specified.
• UV-Vis characteristics: Not specified for this item; refer to CoA/Spec Sheet.
• Solubility (water/organic): Not specified for this item; refer to CoA/Spec Sheet.
• LogP / pKa: Not specified for this item; refer to CoA/Spec Sheet.

General expectations for BACE1 inhibitor tool compounds (literature/general)

• Physical form is commonly an off-white to light-colored solid with moderate to low aqueous solubility; DMSO is typically used to prepare concentrated stocks (e.g., 10–50 mM), followed by dilution into assay buffers with ≤1–2% final DMSO.
• Many BACE1 inhibitors display multiple heteroatoms (H-bonding capacity) and moderate polarity; ionizable groups may be present, influencing pH-dependent solubility. Always verify with item-specific data.

Practical guidance

• Perform a micro-solubility screen (DMSO, DMF, ethanol, aqueous buffers at pH 2–9 with 0.01–0.1% non-ionic surfactant if permitted) to establish working concentrations.
• For spectroscopic or chromatographic characterization, consult the CoA for recommended analytical methods (HPLC conditions, detection wavelengths). All definitive values should be taken from the product’s CoA/Spec Sheet.

Quality and Grades

Item-specific quality information

• Grade/Purity: Not specified for this item; refer to CoA/Spec Sheet.

How to interpret grade/purity (general guidance)

• Research grade small-molecule inhibitors are typically qualified by HPLC purity (area%) and identity confirmation (LC–MS and/or NMR). Low-level residual solvents, water content (Karl Fischer), and inorganic residues may be reported on the CoA.
• If “HPLC grade” is mentioned for solvents, it implies low UV background; for solid inhibitors, “≥95% (HPLC)” or higher thresholds are common. Absence of a stated assay requires consulting the lot-specific CoA for exact purity and analytical methods.

Stabilizers and formulation

• Stabilizers, salts, or counter-ions (if any) impact solubility and stability; none are specified for this item. Verify whether the material is the free base/acid, salt form, or solvate on the CoA.

Recommended verification by end users

• Confirm identity by LC–MS and purity by analytical HPLC using your method. If optical activity is relevant, obtain chiral HPLC or optical rotation data.
• For bioassay use, perform a small-scale pre-test to ensure activity in your assay matrix (enzyme source, buffer composition, DMSO content). Document lot-to-lot comparability using a standard reference curve of enzymatic inhibition.

Reaction and Applications

This product is provided as a research tool compound for biochemical assays rather than as a synthetic reagent.

Applications (research use; no medical claims)

• Enzymology: Evaluation of BACE1 (beta-secretase 1) inhibition in purified enzyme or cell-based reporter assays to study APP processing biochemistry. Enables structure–activity relationship (SAR) comparisons when used alongside analog sets.
• Chemical biology: Use as a probe compound to modulate BACE1 activity in mechanistic studies, target engagement assays (e.g., CETSA), or pull-down experiments when derivatized with linkers (derivatization not provided with this item).
• Screening workflows: Serves as a reference/positive control in assay development once potency is verified in-house.

Not typically applicable

• This compound is not commonly used for catalytic, organometallic, or named synthetic reactions. If derivatization is desired (e.g., for probe development), consult your medicinal chemistry group for route scouting based on the definitive structure from the CoA.

Practical tips

• Verify activity in your assay buffer composition (ionic strength, pH, detergents) and at your intended DMSO percentage, as BACE1 activity is sensitive to assay conditions (literature/general).
• Include counterscreens (e.g., unrelated proteases) to assess selectivity profile in your system. Record full concentration–response curves and report Hill slopes to identify aggregation or non-specific effects.

Reaction Conditions

Chemical reaction conditions are not generally applicable to this item as it is supplied for biochemical inhibition studies rather than for use as a reagent.

Assay conditions for enzymology (general; literature-based guidance)

• Temperature: 25–37°C is typical for in vitro enzyme assays; maintain strict control and pre-equilibrate plates to reduce edge effects.
• pH: Acidic buffers (e.g., pH 4.5–5.5) are commonly used for BACE1; verify the pH optimum for your enzyme preparation and substrate.
• Substrate: Fluorogenic peptides with the APP beta-site sequence are widely used. Validate Km and choose substrate concentrations near Km to sensitively detect competitive inhibition.
• Solvent: Maintain constant DMSO (often 0.1–1.0% v/v) across all wells. Prepare BACE1-IN-4 stock in DMSO and dilute into buffer immediately before use to minimize precipitation.
• Incubation: Preincubate enzyme with inhibitor (e.g., 10–30 min) before initiating reactions to approach steady-state inhibition, especially for tight binders.
• Controls: Include no-inhibitor (vehicle), no-enzyme, and positive inhibitor controls. Generate full concentration–response curves (≥10 points, 1:3 serial dilutions) for robust IC50 estimation.

Data integrity

• Monitor for assay interference (inner filter effects in fluorescence, compound autofluorescence, aggregation). Counterscreens and orthogonal readouts (e.g., HPLC-based product quantitation) are advisable.

Item-specific potency or assay-validated conditions are not provided in this listing; optimize empirically.

Safety and Handling

Item-specific hazard data

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

General laboratory safety (guidance; defer to SDS)

• Handle in a chemical fume hood, avoiding dust generation and aerosolization. Use standard PPE: lab coat, safety glasses, and appropriate chemical-resistant gloves (e.g., nitrile). Avoid ingestion, inhalation, and skin/eye contact.
• Storage incompatibilities: Keep away from strong oxidizers and strong acids/bases unless stability is verified. Protect from moisture and light if the compound is reported as photosensitive or hydrolytically labile (check CoA/SDS).
• Spill/Exposure: For small spills, avoid dust, collect with inert absorbent, and dispose per institutional chemical waste procedures. In case of contact, rinse affected area with water for 15 minutes; seek medical attention according to SDS guidance.
• Fire safety: For organic solids, CO2, dry chemical, or foam extinguishers are typically appropriate. Thermal decomposition may produce irritating/toxic fumes; firefighters should wear SCBA.

Storage and transport (item-specific where provided)

• Storage conditions: Store at −20°C (per Product Data). Keep tightly closed in original container. Minimize freeze–thaw by preparing working aliquots.
• Shipping: Shipped in ice chest with ice pads (per Product Data). Inspect upon receipt; allow to equilibrate in desiccator prior to opening to avoid condensation.

Solvent Selection

Item-specific solubility: Not specified for this item; refer to CoA/Spec Sheet.

General solvent strategy for small-molecule inhibitors

• Primary stock solvent: DMSO is commonly preferred due to broad solvency and bioassay compatibility at ≤1–2% v/v final concentration.
• Secondary options: DMF, ethanol, methanol, or 1:1 DMSO:water co-solvent systems can be evaluated if DMSO solubility is limited. For aqueous use, gentle warming (≤40°C) and sonication can assist dissolution; avoid prolonged heating.
• pH adjustment: If the compound contains ionizable groups (unknown here), modest pH adjustment (buffer pH 2–3 for bases or pH 8–9 for acids) can enhance solubility during intermediate dilutions. Always return to the assay’s physiological pH before testing.

Polarity and miscibility (general)

• DMSO is fully miscible with water and many organics, facilitating serial dilutions. Ethanol and methanol are miscible with water but can perturb some enzyme assays at higher percentages; validate tolerances.

Decision points

• Choose DMSO stocks when bioassay is the goal and compound stability permits.
• Consider ethanol for organismal or membrane assays sensitive to DMSO, within tolerated limits (e.g., ≤0.5%).
• Employ co-solvent with non-ionic surfactant (e.g., 0.01–0.05% Tween-20) only if permitted by your assay and after control validation, as surfactants can affect enzyme kinetics.

Documentation

• Record exact solvent, concentration, and dilution sequence, as solubility artifacts are a common source of variability in enzymatic inhibition data.

Storage and Reconstitution

Item-specific storage and shipping

• Storage conditions: Store at −20°C (per Product Data). Keep tightly capped in the original container. Protect from moisture; allow vials to equilibrate to room temperature in a desiccator before opening to prevent condensation.
• Shipped in: Ice chest with ice pads (per Product Data). Inspect for container integrity upon receipt.

Reconstitution (general guidance; verify with CoA)

• Solvent: DMSO is commonly used for small-molecule inhibitor stocks. If DMSO is unsuitable for your application, evaluate DMF, ethanol, or buffered aqueous systems compatible with the assay.
• Concentration: Prepare a concentrated stock (e.g., 10–50 mM) to minimize solvent in the final assay. Confirm complete dissolution visually; if needed, sonicate briefly and avoid prolonged heating.
• Filtration: If particulate matter persists, pass through a 0.22 µm PTFE syringe filter.

Handling and stability

• Aliquot to single-use vials to avoid repeated freeze–thaw cycles. Record preparation date, solvent, and concentration on each aliquot.
• Short-term bench stability during assay setup (hours) is typically acceptable for many inhibitors, but item-specific stability is Not specified for this item; refer to CoA/Spec Sheet.
• For long-term storage of solutions, keep at −20°C or below and protect from light; periodically re-check purity by analytical HPLC/LC–MS.

Note

• Research use only. For definitive specifications (purity, counter-ion, water content, exact solubility/stability), consult the lot-specific CoA/Spec Sheet and SDS.

Structure and Identity

• SKU: B1445268
• Product name: BACE1-IN-4 (research tool compound)
• CAS: 2361157-92-6
• Category Path: 全部 / 可售 / 小分子和化合物库

Item-specific identifiers

• 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.
• InChI / InChIKey: Not specified for this item; refer to CoA/Spec Sheet.
• Synonyms: Not specified for this item; refer to CoA/Spec Sheet.

General structural notes (literature/general)

• BACE1-IN-4 denotes a small-molecule inhibitor designed to modulate the aspartyl protease BACE1 (beta-site APP cleaving enzyme 1). Such inhibitors commonly feature heteroaromatic scaffolds and hydrogen-bond donors/acceptors arranged to engage the catalytic aspartates and flap region of BACE1; exact features for this catalog item are not specified here.

2D structural description (general)

• As a small-molecule inhibitor, the 2D structure typically comprises an aromatic/heteroaromatic core with appended polar functionality to provide protease-binding interactions; however, the precise ring systems, stereochemistry, and substituent pattern for CAS 2361157-92-6 are not provided in this listing. Please consult the CoA/Spec Sheet for definitive structure, stereochemical assignments, and analytical identifiers.

Synthetic Utility

This listing pertains to a finished small-molecule research tool, not a synthetic building block. As such, it is not typically leveraged for routine synthetic transformations.

General considerations (if derivatization is pursued)

• Probe development: Researchers sometimes derivatize bioactive inhibitors to append linkers (e.g., biotin, fluorophores) for affinity capture or imaging. Feasibility depends entirely on the molecule’s functional handles (not specified here). Derivatization should preserve interactions with BACE1’s active site and minimize perturbation of key pharmacophores.
• Prodrugs/salts: Formation of salt forms (e.g., HCl for basic centers) may modulate solubility for certain assays; confirm structural compatibility from the CoA.

Not typically applicable

• There are no standard named reactions or cross-coupling roles associated with this product as supplied. For synthetic route exploration to analogs, consult medicinal chemistry references once the definitive structure is available.

Recommendation

• If chemical modification is intended, obtain the full structural and analytical dossier (NMR, MS, purity, counter-ions) for the specific lot, then perform retrosynthetic analysis to identify derivatization points that do not abrogate BACE1 binding.

Target Specificity

Item-specific targeting data

• Primary target, potency metrics (IC50/Ki), and panel selectivity for BACE1-IN-4 are not specified for this item; refer to the CoA/Spec Sheet and to peer-reviewed literature where applicable.

General background (literature/general)

• Intended target class: Aspartyl protease BACE1 (beta-site APP cleaving enzyme 1). Typical selectivity concerns include BACE2 and other aspartyl proteases (e.g., cathepsin D). Off-target profiling using biochemical panels and cellular assays is recommended.

Recommended characterization workflow

• Biochemical potency: Determine IC50 under standardized conditions; if mechanism is competitive, consider Cheng–Prusoff correction to estimate Ki using measured Km.
• Selectivity: Run tiered counterscreens (BACE2, cathepsin D/E) at matched conditions.
• Cellular target engagement: CETSA, target occupancy assays, or reporter-based APP processing systems can corroborate target modulation.
• Aggregation/artifacts: Include detergent controls and DLS or AMP (aggregator) panels to detect colloidal behavior at higher concentrations.

Documentation

• Report full assay conditions, including buffer composition, pH, temperature, enzyme and substrate concentrations, and DMSO percentage to enable cross-lab reproducibility.