PROTAC CRABP-II Degrader-2 , CAS No.1225383-38-9

CAS: 1225383-38-9 Cat. No.: P1448428 Fórmula: C₄₄H₆₄N₄O₁₀ Peso molecular: 809.00

Storage

Store at -20°C

Shipped In

Ice chest + Ice pads

Visão geral

PROTAC CRABP-II Degrader-2 is a potent cellular retinoic acid binding protein ( CRABP-II ) degrader based on IAP ligand.

Specifications

Condições de armazenamento de armazenamento

Store at -20°C

Enviado em

Ice chest + Ice pads

Este produto requer transporte de cadeia fria. Serviços terrestres e outros serviços econômicos não estão disponíveis.

Nomes e identificadores

Peso molecular

809.00

Application Protocols

No tested application protocols are provided for this specific item. The following are general, non-item-specific guidelines for small-molecule degraders in cell culture assays.

General workflow (to be optimized by user):

• Prepare a sterile DMSO stock (e.g., 10 mM as solubility allows). Filter if appropriate and chemically stable.
• Treat cells with a dilution series (e.g., 0.01–10 µM; user to optimize) keeping final DMSO constant across wells.
• Incubate for selected time points (e.g., 2, 6, 16, 24 h) and harvest for analysis.
• Readouts: Western blot or targeted MS for CRABP‑II; qPCR or reporter assays for downstream retinoid signaling; cell viability to assess nonspecific cytotoxicity.
• Mechanism controls: include proteasome/neddylation inhibitors and component controls (E3 binder alone, target ligand alone) as available.

Important: These steps are general literature practices and not validated for this specific SKU. Users must establish conditions empirically.

Biological Roles

Context for the intended target (general biology; not item-specific claims):

• CRABP‑II (cellular retinoic acid‑binding protein II) is a cytosolic lipid‑binding protein that binds retinoic acid and can influence its delivery to nuclear receptors (e.g., RARs), thereby modulating retinoid signaling pathways regulating differentiation and gene expression.
• Chemical degraders targeting CRABP‑II are used to acutely diminish CRABP‑II protein levels, enabling studies on the role of retinoid trafficking and signaling.

Potential experimental readouts (general):

• Quantification of CRABP‑II protein levels by Western blot or targeted proteomics after treatment.
• Assessment of retinoic acid–responsive transcriptional reporters.
• Rescue controls using proteasome/neddylation inhibitors to confirm PROTAC mechanism.

Important notes:

• No biological potency, selectivity, or proteomics data are provided for this specific item. Users must establish dose–response, time-course, and off‑target profiling in their own systems.
• Research use only. Not for diagnostic, clinical, or therapeutic use.

Buffer Applications

This product is not a buffering reagent. It does not define or maintain pH in biochemical systems.

Practical guidance for assay buffers (general for small-molecule screening):

• Use standard biological buffers suitable for your assay (e.g., HEPES, PBS) and add the compound from a DMSO stock to the desired final concentration while maintaining a constant DMSO percentage across controls.
• If solubility is limited, consider adding non-ionic surfactants at low percentages or using carrier proteins (e.g., low % BSA) to minimize adsorption, provided they do not interfere with readouts.

No item-specific buffer recipes or pH ranges are provided for this product.

Green Alternatives

As a bioactive probe, the main environmental footprint arises from solvent usage during handling, storage, and assay preparation rather than from the compound’s function.

Greener handling considerations (general):

• Prefer minimal DMSO volumes and use microformatting to reduce waste.
• Consider aqueous-first formulations with small amounts of co-solvent and biocompatible solubilizers (e.g., cyclodextrins) when compatible with assays.
• Use closed, low-evaporation plates to limit solvent emissions.

Comparison of common solvents for PROTAC stock preparation (general literature):

• DMSO: excellent solvency; moderate environmental/health footprint; widely accepted in screening. Waste should be collected as halogen-free organic waste.
• PEG‑400 or aqueous cyclodextrin vehicles: greener profile for in vitro work; may alter compound activity or bioavailability—requires validation.
• Ethanol/water mixes: greener but often insufficient for high-MW degraders.

Operational green tips:

• Scale stocks to realistic assay throughput to minimize expired waste.
• Use reusable glass vials and low-binding plastics to reduce losses and plastic waste.

Item-specific green alternatives are not applicable because exact solubility/stability data are not provided.

Pharmaceutical Uses

This product is supplied strictly for research use and is not an excipient or a GMP-grade material.

General context (non-clinical):

• PROTAC-class molecules are often explored in discovery research for targeted protein degradation in cellular or biochemical models. Formulation work in this space typically focuses on DMSO stocks for in vitro assays.
• No pharmacopeial monograph, dosage form, or excipient role is indicated for this item.

Item-specific regulatory/quality status:

• No pharmaceutical or clinical use is claimed or supported. For any translational work, users must source appropriate GMP materials and conduct full safety/tox studies independently.

Physical Properties

Item-specific physicochemical data are not supplied in this record.

• Appearance: Not specified for this item; refer to CoA/Spec Sheet.
• Molecular weight: Not specified for this item; refer to CoA/Spec Sheet.
• Melting/boiling point: Not specified for this item; refer to CoA/Spec Sheet.
• Density: 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.
• Refractive index/UV cutoff: Not specified for this item; refer to CoA/Spec Sheet.

General guidance for PROTAC-class molecules (literature/general):

• Many PROTACs are high-MW, polar, and amphiphilic, with limited aqueous solubility but good solubility in polar aprotic organics (DMSO, DMF). Stock solutions are commonly prepared in dry DMSO and diluted into assay buffer with co-solvent control.
• Hygroscopicity can vary; protect from moisture and light where feasible.
• Because PROTACs often contain multiple H‑bond donors/acceptors (e.g., amide/urea/ether groups), they may show partial aqueous solubility when aided by surfactants or small percentages of co-solvent.

Always verify item-specific data on the CoA prior to critical use.

Quality and Grades

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

Interpretation and implications:

• In the absence of a stated “grade” (e.g., screening library grade, >95% HPLC, or medicinal chemistry grade), users should consult the CoA for the actual purity metric, analytical method (HPLC/UPLC with UV/ELSD/MS), and residual solvent profile.
• For targeted protein degraders used in cellular assays, a typical expectation is high chemical purity and low residual metals/solvents; however, specific item values are not provided here and must be confirmed on the CoA.
• If a stabilizer, form (free base vs. salt), or counterion is used, it would be indicated on the CoA. Nothing is specified in this listing.

Recommended verifications upon receipt:

• Request/retain CoA and lot-specific chromatograms. Confirm identity by LC–MS and, if needed, NMR before long studies.
• If using in screening panels, consider reformatting into DMSO stocks under low-moisture, low‑oxygen conditions to minimize degradation.
• Perform functional QC in-house (e.g., target engagement/ternary complex assay) if the application requires mechanistic confirmation.

Reaction and Applications

This compound is intended as a functional chemical probe for targeted protein degradation, not as a general synthetic reagent.

Research applications (general for CRABP‑II degraders/PROTACs):

• Study of CRABP‑II protein homeostasis by induced ubiquitination and proteasomal degradation.
• Time-course evaluation of degradation kinetics (DC50/Dmax) in relevant cell lines; comparison with non-degrading analogs or E3-recruiter controls.
• Pathway interrogation: effects on retinoid signaling and downstream gene expression once CRABP‑II levels are modulated (general biological inquiry; not medical use).

Practical tips (general):

• Prepare concentrated DMSO stocks under dry, inert conditions if feasible; aliquot to avoid repeated freeze–thaw.
• Include controls: inactive epimer, E3 ligase binder alone, or target binder alone to confirm PROTAC-specific effects.
• Validate proteasome dependence using proteasome inhibitor rescue and/or neddylation blockade (e.g., MLN4924), as appropriate for mechanistic studies.

Note: No item-specific application data (assay conditions, concentrations, degradation metrics) are provided in the listing; users should establish conditions empirically.

Reaction Conditions

Not a synthetic reagent; reaction condition guidance is generally not applicable.

For biological assays (general operational conditions):

• Stock solutions: commonly prepared in anhydrous DMSO; concentration determined by solubility and assay needs. Item-specific solubility is not provided.
• Working concentrations: established empirically via dose–response; include vehicle controls.
• Incubation: time courses ranging from 1–24 h (or longer) are often used in degradation studies; actual conditions must be optimized per cell type and readout.
• Controls: proteasome and neddylation inhibitors can help confirm degradation mechanism; non-degrading analogs or E3 recruiter alone serve as additional controls.

No item-specific assay conditions, temperatures, or expected outcomes are provided in this listing.

Safety and Handling

Safety data specific to this SKU are not fully provided in the listing.

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

General laboratory precautions (good practice):

• Handle as a research chemical of unknown toxicity. Avoid inhalation, ingestion, and skin/eye contact. Work in a certified chemical fume hood.
• PPE: lab coat, safety glasses, and suitable chemical-resistant gloves (e.g., nitrile). For weighing powders, consider dust mask/respirator per risk assessment.
• Solvent considerations: If preparing solutions in DMSO/DMF, note that these can enhance dermal absorption—avoid skin contact.
• Incompatibilities (general): Strong oxidants and strong acids/bases may degrade complex heterobifunctional molecules; avoid excessive heat and prolonged light exposure unless stability is documented.
• First aid (overview; defer to SDS):
  • Skin/eye contact: Rinse with water for ≥15 minutes; remove contaminated clothing; seek medical attention if irritation persists.
  • Inhalation: Move to fresh air; seek medical attention if symptoms occur.
  • Ingestion: Rinse mouth; do not induce vomiting; seek medical attention.

Always consult the product SDS for authoritative hazard, handling, and spill/accidental release procedures.

Solvent Selection

This product is a bioactive small molecule (PROTAC). Solvent choice is typically driven by assay context rather than synthetic use.

• Likely primary solvent (general practice): DMSO for stock solutions due to good solvating power for high-MW, polar–amphiphilic degraders. Item-specific solubility is not provided.
• Co-solvent strategies (general):
  • For aqueous assays, dilute DMSO stocks into buffer to final DMSO ≤0.1–0.5% v/v as allowed by the biological system.
  • If precipitation is observed, small percentages of co-solvents (ethanol, PEG‑400) or surfactants (Tween‑20, Pluronic F‑127) may help; validate for your system.
• Alternatives to consider (tradeoffs):
  • DMF: similar solvating power; higher cytotoxicity risk than DMSO in some systems.
  • Acetonitrile/ethanol: may be acceptable as minor co-solvents; watch volatility and cytotoxicity.

Comparison (general characteristics):

• DMSO: high polarity/protic interaction capability; enhances solubility; can permeabilize membranes.
• PEG‑400: non-volatile, useful as secondary co-solvent; viscosity can complicate pipetting.

Always confirm actual solubility, stability, and adsorption to plastics/glass empirically for this specific item.

Storage and Reconstitution

• Storage conditions (item-specific): Store at −20°C.
• Shipping (item-specific): Shipped in ice chest with ice pads to maintain cold chain.
• Form/appearance: Not specified for this item; refer to CoA/Spec Sheet.

General reconstitution guidance for PROTACs:

• Allow vial to equilibrate to room temperature in a desiccator before opening to minimize moisture condensation.
• Prepare concentrated stock solutions in anhydrous DMSO. Actual achievable concentration depends on solubility (not specified for this item).
• Aliquot stocks to single‑use portions; store tightly sealed at −20°C or below. Protect from light if the structure contains photosensitive motifs (unknown for this item).
• Avoid repeated freeze–thaw cycles; thaw on ice and promptly return unused aliquots to storage.
• For aqueous working solutions, add DMSO stock to buffer under vigorous mixing to minimize precipitation; use immediately or per stability testing.

Stability/shelf life: Not specified for this item; refer to CoA/Spec Sheet.

Research use only: For laboratory research use; not for diagnostic or therapeutic applications.

Structure and Identity

Brief overview: This listing refers to a heterobifunctional small molecule designed for targeted protein degradation of CRABP‑II (cellular retinoic acid‑binding protein II) via a PROTAC mechanism. Item‑specific identifiers are largely not provided in the current record.

• SKU: P1448428
• Product name: PROTAC CRABP-II Degrader-2
• CAS: 1225383-38-9 (as provided)
• 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 PROTAC architecture; general knowledge):

• PROTACs are typically composed of: (a) a target ligand (here, intended for CRABP‑II), (b) a linker (alkyl/PEG/etc.), and (c) an E3 ligase recruiter (e.g., VHL-, CRBN-, or IAP‑binding motif). Exact motifs for this item are not specified in the listing.
• Expected 2D description (general): two pharmacophores connected by a flexible linker bearing multiple heteroatoms; likely contains amide/ether motifs typical of PROTAC designs. Item‑specific functional groups are not provided.

Identity confirmation:

• For definitive identity and structural confirmation, consult the product’s CoA/SDS and analytical data (NMR, HRMS, HPLC).

Synthetic Utility

This listing is for a finished bioactive degrader rather than a synthetic building block. As such, it is not typically used as a reagent in organic synthesis.

Contextual utility in chemical biology (general):

• Serves as a chemical probe to test the degradability of CRABP‑II and to evaluate downstream biological consequences of transient protein removal.
• Can assist in structure–activity relationship (SAR) campaigns: by comparing activity with analogs (linker length/chemistry, E3-ligase recruiter variants), researchers can map design space for CRABP‑II degradation.
• May be used to benchmark new degrader modalities (molecular glues vs. PROTACs) in retinoid-binding protein contexts.

If derivatization is desired (general guidance):

• Researchers sometimes append reporter tags (biotin/fluorophore) to PROTACs via the linker for pull‑down or imaging; such work requires custom synthesis and validation as tags can abolish activity.

Note: No synthetic route, functional group list, or reactive handles are provided for this specific item.

Target Specificity

Only product-data-supported details are provided here.

• Intended target per product name: CRABP‑II (cellular retinoic acid‑binding protein II). However, no validated target-binding data, degron/E3 recruiter identity, selectivity panel, or species cross-reactivity are provided in the listing.
• Clone/isotype/epitope: Not applicable (small molecule degrader).

Item-specific target validation metrics (e.g., DC50, Dmax, proteomics): Not specified for this item; refer to CoA/Spec Sheet or contact technical support for available data.