NX-2127 - ≥98% , CAS No.2416131-46-7

CAS: 2416131-46-7 Cat. No.: N646876 Summenformel: C₃₉H₄₅N₉O₅ Molekulargewicht: 719.83

QUALITÄT & REINHEIT ≥98%

Storage

Protected from light,Store at -80°C

Shipped In

Dry ice packs + Cold packs

Übersicht

NX-2127 is an orally and potent BTK inhibitor, inducing degradation of the mutated BTK C481S in cells. NX-2127 inhibits proliferation of BTK C481S mutant TMD8 cells, more effectively than Ibrutinib . NX-2127 catalyzes the degradation of Ikaros (IKZF1) and Aiolos (IKZF3) with of 25 nM and 54 nM, respectively. NX-2127 stimulates T cell activation and increases IL-2 production in primary human T Cells.

In Vitro

NX-2127 inhibits proliferation of BTK-C481S mutant TMD8 cells with an EC 50 value <30 nM. NX-2127 increases IL-2 production in primary human T Cells. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

In Vivo

NX-2127 (1 mg/kg; po; once daily for 14 days) demonstrates potent degradation of BTK in cynomolgus monkeys in vivo . NX-2127 (po) leads to dose-proportional exposure in plasma and BTK degradation to <10% of baseline levels in circulating and splenic B cells . NX-2127 results in superior tumor growth inhibition (TGI) in both WT TMD8 and C481S mutant xenograft models in mouse . MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Form:Solid

Spezifikationen

Spezifikationen & Reinheit

≥98%

Biochemische und physiologische Mechanismen

NX-2127 is an orally and potent BTK inhibitor, inducing degradation of the mutated BTK C481S in cells. NX-2127 inhibits proliferation of BTK C481S mutant TMD8 cells, more effectively than Ibrutinib ( HY-10997 ). NX-2127 catalyzes the degradation of Ikaros

Storage

Protected from light,Store at -80°C

Verschickt in

Dry ice packs + Cold packs

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

Aktionsart

INHIBITOR

Reinheit

≥98%

Namen und Kennungen

Molekulargewicht

719.83

Chemische und physikalische Eigenschaften

• Löslichkeit: DMSO : 100 mg/mL (138.92 mM; Need ultrasonic)

Application Protocols

No validated, item-specific application protocols are provided in the Product Data for SKU N646876.

General workflow suggestions for small-molecule degraders (informational; not specifications):

• Prepare single-use DMSO aliquots (e.g., 10–20 mM), store at –80°C protected from light.
• Titrate across a broad range (e.g., 3–10 half-log dilutions) to capture both the ascending and hook regions of the curve.
• Monitor target levels via Western blot or targeted MS at multiple time points (e.g., 1, 3, 6, 24 h), normalizing to housekeeping proteins.
• Include orthogonal readouts (e.g., activity assays, phenotypic endpoints) and mechanism controls (proteasome inhibition, ligand competition).

For detailed, fit-for-purpose protocols, develop and qualify methods within your laboratory setting.

Biological Roles

No biological mechanism or targets are specified in the Product Data for this SKU. The following context reflects general literature information about this class of molecules and should not be interpreted as item-specific specifications.

• Mode of action (general for degrader chemistry): Heterobifunctional degraders simultaneously bind a protein of interest and an E3 ubiquitin ligase, facilitating ternary complex formation, ubiquitination, and proteasome-dependent degradation of the target protein.
• Selectivity determinants: Emerge from cooperative binding in the ternary complex rather than solely from binary affinity; linker length/composition and exit vectors are critical.
• Kinetic signatures: Degraders often show bell-shaped concentration–response curves (hook effect) and can decouple occupancy from functional effect, enabling catalytic knockdown.
• Systems biology impacts: Acute protein removal allows interrogation of signaling pathway dependencies, feedback loops, and compensatory mechanisms without genetic perturbation.
• Off-target considerations: E3 ligase recruiters (e.g., cereblon binders) may induce degradation of neosubstrates; broad proteomics is recommended to profile selectivity.

For this catalog item, consult the CoA/Spec Sheet and your institutional SDS for any available, specific details. Perform target verification and mechanism controls (e.g., proteasome inhibitors, excess ligands) in your system.

Buffer Applications

This product is a small-molecule research compound and is not a buffering agent. Therefore, classical buffer system guidance (pKa, buffering range, formulation recipes) is not applicable.

Practical notes for assay buffers (general):

• Use standard biological buffers (e.g., PBS, HBSS, HEPES) suitable for your cell system, and add compound from DMSO stock to achieve the desired final concentration while keeping DMSO low (typically ≤0.1–0.5% v/v).
• Include surfactant (e.g., 0.01–0.1% Tween 80) or protein (e.g., 0.1–1% BSA or serum) if precipitation or adsorption is observed.
• Filter sterilize working solutions where compatible and test for adsorption to plastics; low-binding tubes and plates can improve dose fidelity.

Item-specific buffering parameters are not applicable and are not provided.

Green Alternatives

As a finished research compound, NX-2127 itself does not have a direct “green alternative.” However, greener practices can be applied to its handling and analysis.

Greener handling choices (general guidance):

• Solvent minimization: Use the lowest feasible DMSO concentration in working solutions; plan experiments to reduce waste volume.
• Greener chromatography: Prefer water/acetonitrile systems over chlorinated solvents for analytical HPLC/UPLC. Optimize gradients to shorten run times and reduce solvent consumption.
• Energy-efficient storage: Consolidate aliquots and minimize freezer door openings; maintain inventory to avoid unnecessary shipments.
• Waste reduction: Pool compatible organic wastes; avoid halogenated solvents unless required.

Comparison (contextual):

• DMSO vs. DMF/NMP: DMSO is generally preferred for toxicity and regulatory profiles; DMF/NMP have higher worker-safety concerns. Where possible, maintain DMSO as the primary solvent.
• Acetonitrile vs. methanol: ACN affords lower backpressure and sharper peaks (often shorter runs), potentially reducing solvent use; MeOH has a better environmental profile but may require longer runs. Choose based on total environmental impact in your method.

Note: Any substitution of solvents or workflows must be validated for compound stability, recovery, and biological activity.

Pharmaceutical Uses

This catalog item is supplied strictly for research use only. No clinical, diagnostic, or therapeutic uses are claimed or supported.

Formulation/CMC context (general for small molecules in preclinical research):

• Excipient compatibility (screening): Solubilizers (e.g., Captisol, PEG400, polysorbates), pH adjustment, and co-solvent systems are often explored in discovery settings to enable in vivo pharmacology; all such applications require internal safety review and are outside the scope of this product listing.
• Reference standards: Research compounds may be employed as internal standards or comparators in analytical development after appropriate qualification.
• Pharmacopeial status: No pharmacopeial monograph is implied; none is provided in the Product Data.

For any translational work, develop de novo CMC, toxicology, and regulatory packages independently. This product is not approved for human or veterinary use.

Physical Properties

Item-specific physico-chemical data are not provided in the Product Data.

• Appearance: Not specified for this item; refer to CoA/Spec Sheet.
• Molecular weight (spec): Not specified for this item; refer to CoA/Spec Sheet.
• BP/MP, density, refractive index: Not specified for this item; refer to CoA/Spec Sheet.
• Solubility (spec): Not specified for this item; refer to CoA/Spec Sheet.

General, literature-based expectations for PROTAC-class degraders (context only; not specifications):

• Physical state: Usually solid powders; frequently amorphous or microcrystalline.
• Solubility behavior: Often sparingly soluble in water; typically dissolved in DMSO to prepare concentrated stocks (e.g., 10–20 mM), then diluted into aqueous media with co-solvent or serum proteins to aid dispersion.
• Lipophilicity/polarity: Many degraders exhibit high MW and elevated polar surface area (PSA), with mixed lipophilicity; may show colloidal behavior upon aqueous dilution without appropriate surfactants or protein.
• Stability: Light and oxidative sensitivity can occur due to multiple heteroaromatics and amides; storage under inert headspace, desiccation, and protection from light is often beneficial.

Always verify exact, item-specific values and handling parameters on the CoA/Spec Sheet before experimental planning.

Quality and Grades

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

Context and expectations for small-molecule research compounds:

• Identity confirmation: Typically supported by NMR, LC–MS/HRMS, and HPLC/UPLC purity analysis. For PROTAC-class molecules, multiple rotamers and broadening may be observed in 1H NMR; LC conditions should be reported (column, gradient, detection wavelength).
• Purity notation: Research-grade products commonly specify area% purity by HPLC/UPLC (e.g., ≥95% area by UV at a given nm). If a stabilizer or counter-ion is used, it will be stated on the CoA.
• Residual solvents/metals: Unless explicitly stated, limits are not part of the catalog spec for this item. For trace analyses (e.g., residual palladium from coupling steps), request CoA/Spec Sheet.
• Implications for assays: For cell-based degradation studies, purity and identity are critical to interpret DC50/maximum degradation; confirm lot purity and retain chromatograms.
• Documentation: Always consult the lot-specific CoA/Spec Sheet accompanying SKU N646876 for definitive grade, analytical methods, and any stabilizers or salt forms if applicable.

Reaction and Applications

This product is supplied as a finished research compound (a heterobifunctional degrader) rather than a synthetic reagent. Therefore, it is not typically used as a reaction solvent or building block in routine synthesis.

Research applications (general, literature-based for NX-2127-class degraders; not item-specific claims):

• Targeted protein degradation (TPD): Employed to recruit an E3 ligase to a kinase target, forming a ternary complex that ubiquitinates and directs the target protein to the proteasome.
• Mechanistic studies: Enables exploration of cooperative binding, ternary complex formation, hook effect characterization, and kinetics of degradation vs. inhibition.
• Chemical biology workflows: Time-course degradation in cell lines, washout-recovery experiments, proteomics to assess on/off-target degradation, and structure–degradation relationship (SDR) optimization.

Practical tips (general):

• Prepare concentrated DMSO stocks (e.g., 10–20 mM), filter-sterilize if needed (PTFE or PVDF; check adsorption) and store aliquots at –80°C.
• Minimize freeze–thaw cycles; use amber vials to reduce photodegradation.
• Include vehicle controls to distinguish degradation-driven phenotypes from DMSO or vehicle artifacts.
• Quantify target levels via immunoblot, ELISA, or targeted proteomics; normalize to housekeeping proteins and assess proteasome dependence with MG132 or epoxomicin controls.

For detailed, item-specific application notes, consult primary literature and validate with your system.

Reaction Conditions

As a final research compound, NX-2127 is not employed as a reagent or catalyst; therefore, synthetic reaction conditions are not typically applicable to its use.

Experimental conditions for biological evaluation (general guidance; not item-specific specifications):

• Stock preparation: Dissolve in anhydrous DMSO to 10–20 mM, vortex and, if needed, gently warm (≤40°C) to aid dissolution. Filter through 0.22 µm PTFE/PVDF if sterile solutions are required.
• Cell-based assays: Dose–response ranges often span low nanomolar to micromolar, with a bell-shaped profile (hook effect) at high concentrations. Maintain consistent DMSO across wells.
• Time course: Degradation may be observed within 1–6 h for susceptible targets, with nadir at 6–24 h; recovery after washout is target- and system-dependent.
• Controls: Include proteasome inhibitors, excess E3 ligand or target ligand to verify ternary-complex dependence, and non-degrading analogs where available.

For any synthesis involving related scaffolds (not this item), typical conditions include amide couplings (HATU/DIPEA), palladium-catalyzed cross-couplings in polar aprotic solvents (DMF/DMAc), and mild deprotection conditions to preserve sensitive motifs. These are provided as general literature context only.

Safety and Handling

Safety data specific to this item are not provided in the Product Data. Defer to the SDS for authoritative guidance.

• GHS classification / pictograms / H-statements / signal word: Not specified for this item; refer to SDS.
• Primary hazards (general for small-molecule research chemicals): May cause irritation to eyes/skin/respiratory tract. Avoid inhalation of dust or aerosols. Effects from systemic exposure are insufficiently characterized; handle as a hazardous laboratory chemical.
• PPE: Laboratory coat, safety glasses or face shield, and appropriate chemically resistant gloves (e.g., nitrile). Use in a certified chemical fume hood.
• Engineering controls: Work in a fume hood for weighing, dissolution, and transfers. Employ secondary containment for stock solutions.
• Storage incompatibilities (general): Keep away from strong oxidizers and strong acids/bases that could degrade amide/heterocycle motifs. Avoid prolonged exposure to light and moisture.
• Emergency measures (overview):
  • Skin contact: Wash with soap and water. Remove contaminated clothing.
  • Eye contact: Rinse cautiously with water for several minutes; remove contact lenses if present and easy to do; continue rinsing and seek medical attention.
  • Inhalation: Move to fresh air; seek medical attention if symptoms persist.
  • Ingestion: Rinse mouth; seek medical attention. Do not induce vomiting unless directed by medical personnel.
• Waste: Dispose of solids and DMSO solutions as organic hazardous waste in accordance with institutional and local regulations.

Solvent Selection

Item-specific solubility is not provided; use the following general guidance for PROTAC-class compounds.

• Primary stock solvent: DMSO is typically preferred due to broad solubilizing power for high-MW, heteroatom-rich molecules.
• Auxiliary solvents (co-solvents for formulation): DMF, NMP, ethanol, or PEG400 can assist in intermediate concentrates; aqueous delivery often benefits from surfactants (e.g., 0.01–0.1% Tween 80) or protein (e.g., 0.1–1% BSA) in buffered media.
• Aqueous compatibility: Direct dissolution in water or PBS is often poor; dilute DMSO stocks into pre-warmed media slowly with vigorous mixing to minimize precipitation. Maintain final DMSO ≤0.1–0.5% v/v for sensitive cells.
• Polarity considerations: PROTACs commonly possess both polar (amide/linker) and hydrophobic (aromatic) domains; mixed solvent systems are frequently required.
• Analytical solvents: For LC–MS, water/acetonitrile or water/methanol with 0.1% formic acid are typical. For stability-indicating assays, evaluate multiple pH modifiers (FA, ammonium acetate, ammonium bicarbonate) to detect degradants.
• When to choose alternatives: If DMSO is undesirable, 2-methyl-2-butanol or cyclodextrin complexes may be explored for aqueous delivery; validate activity and stability after any vehicle change.

Storage and Reconstitution

• Storage conditions (from Product Data): Store at –80°C, protected from light.
• Shipping (from Product Data): Shipped on dry ice packs + cold packs to maintain ultra-low temperature.
• Research use only (from Product Data).

Reconstitution and handling (general guidance; verify with CoA/Spec Sheet):

• Allow containers to equilibrate to ambient temperature in a desiccator before opening to avoid condensation.
• Dissolve in anhydrous DMSO to prepare concentrated stocks (e.g., 10–20 mM). Mix thoroughly; gentle warming (≤40°C) can assist dissolution. Do not overheat.
• Dispense into amber, low-bind microtubes as single-use aliquots to minimize freeze–thaw; purge headspace with inert gas if feasible.
• Store aliquots at –80°C, protected from light. Avoid repeated freeze–thaw cycles; discard aliquots showing precipitation, discoloration, or anomalous chromatographic profiles.
• For aqueous working solutions, add DMSO stock slowly to pre-warmed buffer or media with vigorous mixing; confirm clarity and concentration before dosing.

Always consult the lot-specific CoA/Spec Sheet and SDS for any additional instructions, concentration limits, or stability information unique to this item.

Structure and Identity

Overview: NX-2127 is a heterobifunctional small-molecule degrader (PROTAC-class) supplied for research use.

• CAS: 2416131-46-7
• Synonyms: NX 2127 (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-based for PROTACs of this class; not item-specific):

• Bifunctional architecture: Typically comprises a target-binding warhead (e.g., a kinase binder) linked to an E3 ligase ligand (commonly cereblon or VHL) via a flexible linker.
• Functional group diversity: Often includes multiple heterocycles, amide linkages, and hydrogen-bond donors/acceptors to enable high-affinity binding to both protein partners.
• 2D description (generic PROTAC motif): A left-hand heteroaryl/aryl pharmacophore (target binder) — amide/alkyl/PEG-like linker — right-hand imide/imidazolinone-type motif (E3 ligase ligand), arranged linearly.

Important notes:

• No item-specific structure identifiers are provided in the Product Data; consult the CoA/Spec Sheet for definitive identifiers and structural representation applicable to this SKU (N646876).
• For publications discussing NX-2127 as a BTK-directed cereblon-recruiting degrader, consult primary literature/patent sources; do not use literature structures as specifications for this catalog item without verification.

Synthetic Utility

NX-2127 is provided as a finished small molecule and is not commonly used as a building block. Nevertheless, understanding typical functional motifs in degrader chemistry can assist in analytical and stability work.

General functional motifs in PROTACs (context; not item-specific):

• Amide linkages and heteroaryl cores: Susceptible to hydrolysis under strong acidic/basic conditions and to enzymatic cleavage in biological matrices.
• Imide/urea/ether linkers: Potential liabilities toward nucleophiles and oxidative conditions; evaluate stress stability for method development.
• Multiple H-bond donors/acceptors: Influence chromatographic behavior (secondary retention), requiring carefully tuned gradients and buffers.

Analytical/synthetic considerations for related scaffolds:

• Named reactions (for warhead/linker assembly): Amide couplings (HATU/HBTU/EDC), Buchwald–Hartwig or Suzuki couplings for heteroaryl installation, nucleophilic aromatic substitution, and SNAr on activated heteroarenes; late-stage amidation or click-chemistry for linker diversification.
• Protecting-group strategy: Orthogonal protection may be required during multi-step assembly to preserve ligase ligand functionality.

While not intended for further chemical transformation, familiarity with these features aids in degradation of impurities, forced-degradation studies, and stability-indicating method development.

Target Specificity

Item-specific target(s), binding affinities, and degradation profiles are not provided in the Product Data for SKU N646876.

• Target protein(s): Not specified for this item; refer to CoA/Spec Sheet and primary literature if applicable.
• E3 ligase recruiter: Not specified for this item; refer to CoA/Spec Sheet.
• Cell line/organism reactivity: Not specified for this item; refer to CoA/Spec Sheet.

Note: Literature on molecules referred to as “NX-2127” discusses targeted protein degradation of specific kinases via cereblon recruitment; however, these details are not part of the catalog specification and should not be assumed for this item without verification.

Häufig gestellte Fragen

What is the purity of this product?

This product is supplied at ≥98% purity (chemical assay). Lot-specific values are stated on the Certificate of Analysis.

How should this product be stored?

Store at ?80 °C, protected from light. The material is light-sensitive — keep it in its original opaque or amber container.

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 2416131-46-7, the molecular formula is C39H45N9O5, and the molecular weight is 719.83 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.