PROTAC HDAC8 Degrader-1 , CAS No.P1426659

CAS: P1426659 Cat. No.: P1426659 Formula: C₃₂H₄₄N₆O₄ Molecular Weight: 576.73

Storage

Store at -20°C

Shipped In

Ice chest + Ice pads

Overview

Degrader-1 (compound Z16) is a potent and selective HDAC8 PROTAC degrader with an DC 50 of 0.27 nM in A549 cells.

Specifications

Storage

Store at -20°C

Shipped In

Ice chest + Ice pads

This product requires cold chain shipping. Ground and other economy services are not available.

Action Type

DEGRADER

Names and Identifiers

Molecular Weight

576.73

Application Protocols

No tested applications, recommended concentrations, or protocols are provided in the Product Data for this item.

• Validated applications (WB, IF, IHC, FC, cell-based assays), recommended dilutions/concentrations, and positive controls: Not specified for this item; refer to CoA/Spec Sheet.

Suggestion:

• Develop pilot titrations and time-course studies suitable for your model system, with appropriate vehicle controls, but rely on your internal SOPs and the product CoA/SDS for any item-specific instructions.

Biological Roles

Item-specific biological performance data and target selectivity are not provided in the Product Data.

General background (literature/general):

• HDAC8 function: Histone deacetylase 8 is a Zn2+-dependent deacetylase involved in chromatin remodeling and regulation of non-histone substrates. HDAC8 activity influences transcriptional programs and cell-state regulation in diverse contexts.
• PROTAC mechanism: PROTACs co-recruit an E3 ubiquitin ligase to a target protein, catalyzing polyubiquitination and subsequent proteasomal degradation. Unlike inhibitors that require continuous occupancy, degraders can produce sustained target knockdown and impact both catalytic and scaffolding functions of the protein.
• Selectivity considerations: Target degradation profiles depend on ternary complex formation, linker geometry, and ligase choice (e.g., CRBN vs VHL). Off-target degradation may occur and should be assessed by proteomics or panel assays (literature best practices).
• Experimental readouts: Typical endpoints include target protein levels (western blot/ELISA/proteomics), downstream histone acetylation marks, and phenotypic changes. Time-course and concentration–response analyses yield metrics such as DC50 and Dmax (literature definitions).

Caveats:

• Cellular permeability, efflux, and intracellular concentration can strongly affect observed degradation. Serum protein binding and nonspecific adsorption may reduce free concentrations.

Note: For this item, no validated cell lines, DC50/Dmax values, or proteome-wide selectivity data are provided. Consult the CoA/Spec Sheet for any available testing information.

Buffer Applications

This product is a small-molecule degrader and is not used as a buffer component.

Practical notes (general):

• Working solutions are typically prepared in DMSO, then diluted into assay buffers or cell culture media while keeping the final DMSO fraction low (commonly ≤0.1–0.5%, literature practice) to maintain cell viability and assay integrity.
• Buffers for downstream analyses (e.g., lysis, western blot) should include appropriate protease inhibitors and deacetylase inhibitors only if consistent with experimental goals; note that HDAC inhibitors in lysis buffers can confound interpretation of degradation vs inhibition.

Item-specific buffer compatibility, precipitation thresholds, or pH stability: Not specified for this item; refer to CoA/Spec Sheet.

Green Alternatives

Given the nature of this product as a bioactive small molecule/PROTAC for research assays, “green alternatives” typically refer to solvent and handling choices rather than alternative compounds.

• Solvent considerations (general): Prefer minimal DMSO percentages in assays to reduce solvent burden and potential cytotoxicity. Where compatible, consider aqueous buffers with the lowest feasible co-solvent content. Avoid high volumes of DMF/NMP due to toxicity and disposal concerns.
• Process scale: Usage is generally at milligram to microgram scale in discovery settings; environmental impact is driven more by solvent selection and waste segregation than by the compound itself.
• Workflows: Implement microscale assay formats, sealed plates to reduce volatile emissions, and efficient serial dilution schemes to minimize waste. Use glass vials to reduce plastic adsorption and subsequent re-preparations.

Not applicable/limited relevance:

• There are no recognized “green substitute molecules” for a specific PROTAC design without changing biological outcomes. Any substitution would alter target engagement and degradation profile.

Note: Item-specific solvent or stability data are Not specified; refer to CoA/Spec Sheet. Follow institutional green-chemistry policies for solvent selection and waste handling.

Pharmaceutical Uses

No pharmaceutical or clinical use is stated or implied for this research reagent.

• Research Use Only: As per Product Data, this material is for research use only.
• Excipient/formulation role: Not applicable; this is a bioactive small molecule, not an excipient.
• Pharmacopeial status: Not specified for this item; refer to CoA/Spec Sheet.

General note:

• While PROTACs are of interest in drug discovery, this product is supplied solely for laboratory research, screening, and mechanistic studies. It is not intended for human or veterinary use, diagnostic procedures, or as a therapeutic agent.

Physical Properties

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

• Appearance: Not specified for this item; refer to CoA/Spec Sheet.
• Molecular Weight: Not specified for this item; refer to CoA/Spec Sheet.
• Molecular Formula: Not specified for this item; refer to CoA/Spec Sheet.
• Melting point, boiling point, density, refractive index: Not specified for this item; refer to CoA/Spec Sheet.
• Water content, residual solvents, metal content, UV cutoff: Not specified for this item; refer to CoA/Spec Sheet.

General characteristics (literature/general for PROTACs):

• PROTACs frequently have high MW (typically 700–1200 Da, literature) with multiple HBA/HBD and elevated TPSA, leading to low aqueous solubility and preferential dissolution in DMSO.
• Typical stock preparation uses anhydrous DMSO at 10–20 mM; serial dilution into aqueous assay buffers often requires ≤0.1–0.5% DMSO final (literature practice).
• LogP/logD values are highly construct-dependent; PEGylated linkers raise polarity, while alkyl linkers increase lipophilicity (literature trends).

Note: Where exact numerical values are required for method development or QC, please consult the product’s CoA/Spec Sheet and SDS.

Quality & Grades

Item-specific grade/purity is not provided in the Product Data.

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

General considerations for small-molecule library compounds (literature/general):

• Research-grade bioactive molecules are commonly supplied at ≥95% purity by HPLC/UPLC, with identity confirmed by MS and/or NMR. Low-level impurities can affect bioassay readouts, so purity and counter-ion form should be verified prior to critical studies.
• Residual solvent, water content, and salt form (TFA/HCl/acetate) can influence solubility and potency. Confirm by CoA.
• UV transparency (HPLC-grade solvents) and low-fluorescence backgrounds are relevant for analytical characterization but are not item specifications unless stated.
• Stabilizers: None are indicated for this item. If included for some PROTACs (e.g., antioxidants), they should be disclosed on the CoA; absence here means Not specified for this item.

Recommendations:

• Verify batch-specific purity, identity, and salt form on receipt (check CoA/Spec Sheet). For quantitative biology, consider in-house orthogonal checks (LC–MS, qNMR) and test for adsorptive losses on plastics if concentrations are low.

Reaction & Applications

This product is a targeted protein degrader (PROTAC) intended for chemical biology research, not as a synthetic reagent.

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

General applications for an HDAC8-targeting PROTAC (literature/general):

• Mechanism: Induces proximity between HDAC8 and an E3 ubiquitin ligase, promoting ubiquitination and proteasomal degradation of HDAC8. This can yield sustained target knockdown distinct from occupancy-driven inhibition.
• Use cases: Comparative studies versus HDAC8 inhibitors to differentiate catalytic inhibition from protein ablation; ternary complex formation studies; time-dependent degradation and recovery kinetics; proteomics-based selectivity profiling.
• Assay modalities: Cell-based degradation assessment by western blot or quantitative proteomics; time-course profiling to derive Dmax and DC50; washout studies to evaluate resynthesis dynamics. Carefully control DMSO vehicle and include non-degrading controls (e.g., warhead-only, ligase-ligand-only) where available.
• Biophysical characterization: If materials are available, ternary complex formation and cooperativity can be probed by TR-FRET, SPR, or CETSA (general techniques).

Note: No item-specific performance data, EC50/DC50 values, or tested cell lines are provided for this product. Consult the CoA/Spec Sheet for any available characterization.

Reaction Conditions

Not typically applicable. This product is not intended as a reagent for chemical transformations, catalysts, or stoichiometric reactants.

General assay-handling conditions (literature/general for bioactive small molecules):

• Stock preparation: Dissolve in anhydrous DMSO to a convenient concentration (e.g., 10–20 mM). Filter sterilization may be used if compatible with the compound and intended application.
• Working solutions: Dilute into pre-warmed media or buffer with vigorous mixing to minimize precipitation. Final DMSO typically maintained at ≤0.1–0.5% depending on assay tolerance.
• Temperature/light: Handle at ambient temperature during solution prep; protect from prolonged light exposure until compound-specific photostability is known.

Item-specific reaction or assay conditions (e.g., validated concentrations, exposure times, or temperatures): Not specified for this item; refer to CoA/Spec Sheet.

Safety & Handling

Item-specific hazard classification is not provided in the Product Data. Always consult the SDS for authoritative safety information.

• GHS classification, pictograms, signal word, H-statements: Not specified for this item; refer to SDS.
• Storage conditions (from Product Data): Store at −20 °C.
• Shipping: Ice chest + ice pads (from Product Data), indicating temperature sensitivity.

General safety guidance for small-molecule PROTACs (literature/general):

• Handle in a chemical fume hood, avoid inhalation, ingestion, and skin/eye contact. Wear appropriate PPE: lab coat, safety glasses, and chemical-resistant gloves.
• Avoid repeated freeze–thaw cycles of DMSO stocks; aliquot to minimize degradation and contamination.
• Incompatibilities: Strong oxidizers and reducing agents may affect stability depending on functional groups; protect from moisture and light as a precaution until specific stability data are available.
• First aid (overview; defer to SDS): In case of skin/eye contact, rinse with water for ≥15 min; if inhaled, move to fresh air; if ingested, seek medical attention. Remove contaminated clothing.
• Waste: Dispose of solutions and solids as organic hazardous waste per institutional and regulatory guidelines.

Note: Bioactive small molecules may exhibit cytotoxicity or off-target effects; exercise care when preparing and applying concentrated stock solutions.

Solvent Selection

Item-specific solubility data are not provided. The following are general practices for PROTAC-class molecules used in bioassays.

• Primary solvent: Anhydrous DMSO is typically preferred due to the high polarity/HBA-HBD count of PROTACs (literature). DMF or NMP may dissolve some constructs but are less favored in biology.
• Aqueous compatibility: After preparing a concentrated DMSO stock (e.g., 10–20 mM, literature practice), dilute into assay buffer or media while maintaining low final DMSO (commonly ≤0.1–0.5%, per assay tolerance). Add slowly with mixing to minimize precipitation.
• Co-solvents/surfactants: If precipitation occurs on dilution, small amounts of co-solvents (e.g., ethanol) or carrier proteins (e.g., 0.1% BSA) are sometimes used in screening contexts; confirm assay compatibility.
• Adsorption: Some PROTACs adsorb to lab plastics. Glass vials or low-binding plastics can improve recovery at low micromolar–nanomolar concentrations (literature/general).
• Stability: Protect stocks from repeated freeze–thaw and from light until item-specific stability data are available.

Comparison (general):

• DMSO: highest solvating power; excellent for stock prep; biological tolerance at low %.
• Ethanol: moderate solvating power; higher assay interference at >0.5–1%.
• Aqueous buffers: often insufficient for direct dissolution without a co-solvent.

Note: For this item, exact solubility limits and preferred vehicles are Not specified; refer to CoA/Spec Sheet.

Storage & Reconstitution

Item-specific guidance provided in the Product Data:

• Storage Conditions: Store at −20 °C.
• Shipped In: Ice chest + ice pads.

Additional notes (general best practices for small-molecule PROTACs; not item specifications):

• Reconstitution solvent: DMSO is commonly used for initial stock solutions of PROTACs due to solubility; however, the preferred solvent and maximum concentration are Not specified for this item; refer to CoA/Spec Sheet.
• Aliquoting: Prepare single-use aliquots to avoid repeated freeze–thaw cycles. Clearly label concentration, date, and solvent.
• Light/moisture: Store protected from light and moisture until compound-specific stability data are available. Keep containers tightly closed under inert headspace if feasible.
• Handling frozen stocks: Thaw rapidly at room temperature, mix thoroughly to ensure homogeneity, and return unused aliquots to −20 °C promptly. Avoid frost/moisture ingress.
• Stability: Long-term stability, photostability, and solution shelf life are Not specified for this item; consult the CoA/Spec Sheet and perform in-house verification (e.g., LC–MS) if critical to your application.

Research Use: For research use only (per Product Data).

Structure & Identity

Item-specific identifiers: not provided in the Product Data.

• SKU: P1426659
• Product Name: PROTAC HDAC8 Degrader-1
• CAS: P1426659 (catalog placeholder; not a registered CAS number)
• Molecular Formula: Not specified for this item; refer to CoA/Spec Sheet.
• Molecular Weight: 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.

General structural features (literature/general information for PROTACs and HDAC8 ligands):

• PROTACs are bifunctional small molecules comprising: (1) a target-binding ligand (here, an HDAC8-binding “warhead”), (2) an E3 ligase ligand (e.g., CRBN-, VHL-, or IAP-binding), and (3) a flexible linker connecting the two.
• HDAC8 warheads in the literature are commonly hydroxamates or benzamides that chelate the Zn2+ ion in the HDAC8 active site; selectivity can be tuned by cap-group and linker exit vectors.
• The 2D representation typically shows two pharmacophores separated by an aliphatic/PEG/aryl-ether linker; multiple H-bond donors/acceptors and heteroatoms increase polarity/logS versus classical inhibitors.
• Stereocenters may be present in the E3 ligase ligand or linker; regiochemistry of linker attachment is critical for ternary complex formation.

Note: The exact structure, functional groups, and stereochemistry of PROTAC HDAC8 Degrader-1 are not specified for this item; consult the CoA/Spec Sheet for definitive identity data.

Synthetic Utility

This product is supplied as a finished small-molecule degrader for use in chemical biology assays and is not positioned as a synthetic building block.

General considerations (literature/general for PROTAC chemistry):

• Retrosynthetic features: PROTACs are commonly assembled by convergent coupling of a target-binding ligand and an E3 ligase ligand via an amide/urethane/ether linker. Common tactics include NHS ester couplings, click chemistry (CuAAC), and carbonate/urea formations.
• Modularity: Systematic variation of linker length/composition and exit vector enables SAR on degradation efficacy (Dmax, DC50) and selectivity. Warhead modification can switch between occupancy-driven inhibition and degradation competence.
• Analytical support: LC–MS, UPLC, and HRMS are typically used for purity and identity; orthogonal qNMR is useful to confirm mass balance including counter-ions.

Item-specific reactive handles, protecting groups, and intermediate use: Not specified for this item; refer to CoA/Spec Sheet. If your goal is to modify this degrader, obtain structural information and permissions as applicable.

Target Specificity

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

• Primary target, secondary targets, selectivity panel results, and species reactivity: Not specified for this item; refer to CoA/Spec Sheet.

General note (literature/general):

• By name, PROTAC HDAC8 Degrader-1 is expected to be designed to promote degradation of HDAC8; however, this has not been specified or validated in the provided Product Data. Verify target engagement, degradation efficiency, and off-target profiles experimentally and/or via the CoA if available.