cIAP1 Ligand-Linker Conjugates 13 , CAS No.C1448445

CAS: C1448445 Cat. No.: C1448445 Formula: C₃₉H₅₂N₄O₈ Molecular Weight: 704.85

Storage

Store at -20°C

Shipped In

Ice chest + Ice pads

Overview

cIAP1 Ligand-Linker Conjugates 13 incorporates an IAP ligand for the E3 ubiquitin ligase , and a PROTAC linker. cIAP1 Ligand-Linker Conjugates 13 can be used to design SNIPERs.

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.

Names and Identifiers

Molecular Weight

704.85

Application Protocols

This section is not typically applicable to small-molecule building blocks. No tested biological assay protocols, dilutions, or positive controls are specified for this item.

General guidance (literature):

• Stock preparation: 10–50 mM in dry DMSO; store aliquots at −20 °C.
• Working solutions: Dilute into assay medium to final DMSO ≤0.1–0.5% v/v; include vehicle controls.
• Analytical QC: Verify integrity by LC–MS prior to use in biological assays, especially after prolonged storage.

For detailed, application-specific protocols (e.g., ternary complex assays, degradation readouts), consult current literature for IAP-based degrader methodologies.

Biological Roles

Context for researchers (general literature; not item-specific):

• cIAP1 (cellular inhibitor of apoptosis protein 1, BIRC2) is an E3 ubiquitin ligase with BIR (baculoviral IAP repeat) domains and a RING finger. Small-molecule IAP antagonists bind to the BIR domain, displacing native IAP-binding motifs.
• In targeted protein degradation, cIAP1 ligands are used to recruit the cIAP1 E3 ligase to a protein of interest via a bifunctional molecule, enabling ubiquitination and proteasomal clearance.
• Ligand–linker conjugates streamline assembly of chemical probes and degraders by providing a validated E3-binding headgroup with a pre-attached spacer that can be derivatized.

Experimental considerations:

• Ternary complex formation depends on the geometry and flexibility imparted by the linker; systematic variation of linker length/chemistry is often required to optimize degradation efficacy.
• Off-target engagement can occur with cIAP2/XIAP depending on ligand selectivity; orthogonal assays (binding, cell viability, proteomics) are recommended to characterize specificity.

No biological activity, potency, or selectivity values are specified for this item; consult the literature for the particular cIAP1 ligand class you intend to use, and refer to the CoA/Spec Sheet for any available characterization specific to this SKU.

Buffer Applications

This product is not a buffering agent. However, practical notes for preparing assay solutions are provided for convenience (general guidance):

• Stock preparation: Dissolve in anhydrous DMSO (e.g., 10–50 mM). Vortex and, if needed, sonicate briefly. Filter (0.22 µm PTFE) for sterile applications.
• Assay dilution: Add concentrated DMSO stocks into pre-made biological buffers (e.g., PBS, HBSS, HEPES-buffered media) with vigorous mixing to reach a final DMSO content typically ≤0.1–0.5% v/v.
• Detergents: For hydrophobic conjugates that tend to aggregate, 0.01–0.05% nonionic surfactant (e.g., Pluronic F-68 or Tween-20) may improve apparent solubility; confirm compatibility with your assay.
• pH sensitivity: If the conjugate contains hydrolysis-prone moieties (esters/carbonates), avoid prolonged incubation at pH > 8.

Item-specific buffer compatibility and pKa values are not provided for this SKU; consult the CoA/Spec Sheet and perform small-scale solubility/stability checks.

Green Alternatives

While the compound itself is fixed, greener choices can be made in handling and any downstream coupling/purification steps.

Greener process considerations (literature/general):

• Solvents:
  • Prefer ethanol, 2-MeTHF, or CPME where compatible, instead of chlorinated solvents (DCM/DCE) for extractions or couplings.
  • Use water/MeCN gradients for HPLC purification, minimizing modifier percentages; consider supercritical CO2 preparative chromatography when scale permits.
• Coupling reagents:
  • Choose carbodiimides (EDC·HCl) with green additives (OxymaPure) in aqueous-organic media, or enzyme-mediated ligations where appropriate, rather than benzotriazole-based activators.
• Energy and waste:
  • Employ room-temperature couplings and flow chemistry to reduce energy use and improve reagent economy; recover and recycle acetonitrile where facilities exist.

Trade-offs:

• 2-MeTHF/CPME may alter reaction rates/solubility relative to DMF/DCM; ensure compatibility with the ligand–linker solubility and stability.
• Aqueous media can accelerate hydrolysis of labile linkages (esters/carbonates); weigh green benefits against potential degradation.

Summary table (general):

• DCM → 2-MeTHF/CPME: lower toxicity, higher boiling point; check solubility.
• DMF/NMP → propylene carbonate or Cyrene (where feasible): greener profile; watch for viscosity and base compatibility.
• Traditional HATU/HBTU → EDC/Oxyma or DMTMM: reduced hazard; potential changes in coupling efficiency.

Pharmaceutical Uses

No pharmacopeial status or excipient role is specified for this item; it is supplied strictly for research use only.

Context for discovery workflows (general):

• Screening and SAR: cIAP1 ligand–linker conjugates are commonly used as components in the discovery of bifunctional modalities (e.g., IAP-based degraders). They serve as a starting point for medicinal chemistry campaigns but are not finished drug substances.
• Developability profiling: Researchers may assess permeability, stability (microsomal/plasma), solubility, and off-target liabilities of completed bifunctionals derived from this conjugate as part of preclinical research.
• Manufacturing considerations: If scaled for research, attention to residual solvents, salt form selection, and polymorph control can influence formulation experiments; none are specified for this item.

No therapeutic, diagnostic, or clinical claims are made or implied for this product.

Physical Properties

Item-specific physical constants are not provided for this catalog entry.

• Appearance: 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.
• Solubility (general guidance):
  • cIAP1 ligand–linker conjugates are typically soluble in polar aprotic organic solvents (DMSO, DMF, NMP) and variably soluble in methanol/acetonitrile; aqueous solubility usually requires co-solvent or formulation (literature).
• LogP/cLogP, pKa: Scaffold-dependent; not specified for this item; refer to CoA/Spec Sheet.

Practical handling notes (general, literature):

• For screening use, prepare concentrated stocks in anhydrous DMSO (e.g., 10–50 mM) and dilute into assay buffers to ≤0.1–0.5% DMSO v/v to minimize vehicle effects.
• If the conjugate contains hydrolysis-prone linkages (e.g., esters, carbonate, activated haloacetamide), avoid prolonged exposure to aqueous basic media.
• Hygroscopicity and polymorphism are scaffold-dependent; handle quickly at room temperature and return to cold storage as recommended under Storage & Reconstitution.

Quality and Grades

• Grade/Purity: Not specified for this item; refer to CoA/Spec Sheet.
• Research Use Note: For research use only.

Interpretation and implications:

• Research-use-only small-molecule conjugates are intended for discovery chemistry, screening, and method development. They are not produced under GMP and are not intended for human or veterinary applications.
• In the absence of an explicit HPLC/LC–MS purity specification, consult the item’s Certificate of Analysis (CoA) for actual lot-specific purity, identity confirmation (e.g., LC–MS, 1H NMR), and any stabilizers or counterions.
• UV cutoff, water/peroxide/metal content, and residual solvent limits: Not specified for this item; refer to CoA/Spec Sheet.

What to verify on receipt:

• Identity: Lot-specific LC–MS m/z and retention time consistent with the provided structure (when available on CoA).
• Purity: Chromatographic purity and absence of significant hydrolysis products.
• Form: Salt form/free base and hydration state (if applicable), as these impact solubility and calculation of molar concentrations.

If low UV background is important (e.g., bioassays with optical readouts), confirm UV–Vis profile on CoA or generate in-house.

Reaction and Applications

This ligand–linker conjugate is designed for chemical biology and medicinal chemistry workflows that recruit cIAP1, an E3 ubiquitin ligase, as part of bifunctional molecules.

Applications (general, literature):

• Targeted protein degradation (TPD): Assembly of IAP-based PROTACs/SNIPERs by coupling the linker terminus to a target-binding ligand. The conjugate provides the E3 ligase recruiter side pre-installed.
• Probe development: Synthesis of pull-down/affinity probes (e.g., biotinylated or fluorophore-labeled) by extending or derivatizing the linker terminus.
• SAR exploration: Systematic variation of the non-cIAP1 end to map degrader linker length/orientation effects.

Practical tips:

• Maintain anhydrous conditions during conjugation to preserve activated intermediates.
• If the terminal functionality is an amine/carboxyl/azide/alkyne (item-specific handle not provided), select orthogonal chemistries: HATU/EDC for amide; CuAAC for azide–alkyne; NHS esters for rapid labeling; thiol–maleimide for cysteine capture.
• After coupling, purify by preparative HPLC and verify by LC–MS and, where possible, HRMS and 1H/13C NMR.

Assay contexts:

• In vitro binding/ternary complex assays (TR-FRET, SPR) using cIAP1 protein and target ligands.
• Cell-based reporter assays to assess degradation efficacy of completed bifunctionals, controlling DMSO to ≤0.1–0.2%.

Note: No item-specific reactive handle is disclosed here; consult the CoA/Spec Sheet for exact linker terminus and compatible coupling strategies.

Reaction Conditions

Item-specific reaction handles are not provided; the following are general, literature-based conditions commonly used for assembling bifunctional conjugates from ligand–linker intermediates:

• Amide coupling (carboxyl + amine):
  • Solvent: DMF or DCM (anhydrous).
  • Reagents: HATU (1.1–1.5 eq) or EDC·HCl (1.2–1.5 eq) + Oxyma (1.2–1.5 eq); base DIPEA (2–4 eq).
  • Temperature/time: 0–25 °C, 1–16 h. Typical isolated yields: 60–90% (substrate-dependent; literature).
• CuAAC “click” (azide + alkyne):
  • Solvent: tBuOH/H2O (1:1) or DMF/H2O.
  • Catalyst: CuSO4 (5–10 mol%) + sodium ascorbate (10–20 mol%) or CuI (5–10 mol%); 25–40 °C, 1–6 h.
• Thiol–maleimide conjugation:
  • Solvent: PBS or pH 6.5–7.4 buffer with 5–20% acetonitrile.
  • Conditions: Room temperature, 0.5–2 h; avoid excess base to minimize maleimide hydrolysis.
• Carbamate/urea formation:
  • Reagents: CDI or triphosgene equivalents for isocyanate generation; or DSC for carbamate from alcohols.
  • Solvent: DCM/DMF; 0–25 °C.

General tips:

• Maintain anhydrous conditions for moisture-sensitive linkages; monitor by LC–MS.
• Purify by prep HPLC using water/MeCN + 0.1% formic acid or ammonium bicarbonate, depending on downstream assay needs.

All conditions above are literature guidance and not specifications for this item.

Safety and Handling

GHS/SDS details are not provided for this specific item.

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

General laboratory precautions (literature/good practice):

• Handle in a fume hood, avoiding inhalation of dusts/aerosols. Wear appropriate PPE: lab coat, safety glasses, and chemically resistant gloves (e.g., nitrile). For weighed solids, consider antistatic/low-dust techniques.
• Avoid skin/eye contact. In case of contact, rinse with water for at least 15 minutes and seek medical advice per SDS.
• Avoid ingestion and inhalation; do not pipette by mouth. Wash hands after handling.
• Storage incompatibilities: Keep away from strong oxidizers and strong acids/bases if hydrolyzable groups are present (general precaution). Store desiccated to minimize moisture uptake.
• Spill/accident response: Collect solids with minimal dust formation; absorb DMSO/DMF solutions with inert absorbent. Dispose of waste according to institutional and local regulations.

Always consult the official Safety Data Sheet for authoritative hazard, first-aid, and disposal guidance for this SKU.

Solvent Selection

This product is a small-molecule ligand–linker conjugate; solvent choice is driven by solubility, stability, and intended application.

General solvent guidance (literature):

• Primary solvents for stock solutions:
  • DMSO: Broad solubilizing power for heteroaromatic/peptidomimetic conjugates; miscible with water for assay dilution.
  • DMF or NMP: Useful for more hydrophobic conjugates or when higher concentration stocks are needed.
• Secondary solvents/co-solvents:
  • Acetonitrile or methanol: Often suitable for analytical work (HPLC/LC–MS).
  • Aqueous buffers: Use only after preparing a DMSO stock; include 0.01–0.1% nonionic surfactant if needed to minimize aggregation (assay-dependent).

Selection tips:

• Start with 10–20 mM in anhydrous DMSO; check for clarity. If turbid, warm gently (≤40 °C) and sonicate briefly.
• For long-term stocks, avoid repeated freeze–thaw; aliquot.
• For reactions (if further coupling is intended), choose dry, amide-compatible media (DMF, DCM, DCE) and add base/activator appropriate to the coupling chemistry.

Comparison (general):

• DMSO vs DMF: DMSO is preferred for biological assay stocks due to water miscibility and lower volatility; DMF may offer higher solubility for some scaffolds but is less favored in live-cell contexts due to cytotoxicity at comparable percentages.

Storage and Reconstitution

• Storage Conditions (item-specific): Store at −20 °C.
• Shipping (item-specific): Shipped in an ice chest with ice pads to maintain cold chain.

Reconstitution (general guidance):

• Solvent: Use anhydrous DMSO to prepare concentrated stocks (e.g., 10–50 mM). Adjust concentration based on solubility; warm gently (≤40 °C) and vortex/sonicate if needed.
• Aliquoting: Dispense into single-use aliquots in low-binding tubes to avoid repeated freeze–thaw. Flush headspace with inert gas if long-term storage is anticipated.
• Working solutions: Dilute DMSO stocks into pre-chilled assay buffers or media with thorough mixing. Keep final DMSO content as low as assay allows.

Stability precautions (general):

• Protect from moisture and light. Return to −20 °C promptly after use. Avoid prolonged exposure to basic aqueous conditions if hydrolysis-prone linkages are present.
• Monitor integrity periodically by LC–MS/analytical HPLC, especially after >6 months storage.

Any stabilizers, counterions, or exact shelf-life: Not specified for this item; refer to CoA/Spec Sheet.

Structure and Identity

This product is a pre-functionalized small-molecule conjugate designed to recruit the E3 ligase cIAP1 via a known ligand core and present a built-in linker for downstream conjugation or as part of a bifunctional degrader.

• SKU: C1448445
• Product Name: cIAP1 Ligand-Linker Conjugates 13
• Category: Small molecules and compound libraries (screening/chemistry toolbox)
• 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.
• CAS: C1448445 (internal placeholder)

Structural features (general, literature):

• Contains a cIAP1-binding pharmacophore (e.g., derivatives of bestatin methyl ester, LCL161-like, or related IAP antagonists) tethered to a linker terminus suitable for conjugation.
• Typical functional groups in such conjugates include amide(s), carbamate/urea linkages, and one or more heteroaromatic rings; a terminal handle may be an amine, carboxylate, azide, alkyne, or haloacetamide for coupling (literature, not item-specific).
• 2D description (general): an IAP ligand core (aryl/heteroaryl + peptidomimetic motif) connected via a spacer (alkyl/PEG/aryl) to a terminal reactive or cap group. Stereochemistry may be present in the ligand core depending on scaffold (literature).

Synthetic Utility

As a pre-built cIAP1-recruiting headgroup with an integrated linker, this conjugate provides significant value in assembling bifunctional molecules and probes.

Utility (general, literature):

• Rapid assembly of IAP-based degraders by coupling the terminal linker handle to a target-binder (kinase inhibitor, ligand, peptide). This reduces synthetic steps versus de novo installation of the IAP ligand each time.
• Modular diversification: Swapping the target-ligand while keeping the cIAP1 side constant enables efficient SAR on linker length and exit vectors.
• Orthogonal chemistries: Depending on the terminal group (not specified here), typical transformations include:
  • Amide bond formation (EDC/HOBt or HATU/DIPEA) with carboxylic acids or amines.
  • Click chemistry (CuAAC) for azide/alkyne terminals to install triazole-linked payloads.
  • SuFEx or carbonate/urea formation for specific handles.
  • Thiol-specific conjugation (maleimide/haloacetamide) to cysteine-bearing payloads or proteins.

Characterization best practices:

• Confirm integrity of the cIAP1-binding core post-coupling via LC–MS and, if possible, competition binding or thermal shift assays with cIAP1.
• Use 2D NMR (HSQC/HMBC) to verify linkage points in complex bifunctionals.

Note: Exact functional handle and protecting group strategy for this SKU are not specified; consult CoA/Spec Sheet for precise synthetic compatibility.

Target Specificity

This section typically applies to biological macromolecules such as antibodies or affinity proteins. For this small-molecule ligand–linker conjugate, item-specific binding constants, selectivity data, and target panels are not provided.

• Target specificity data: Not specified for this item; refer to CoA/Spec Sheet and primary literature for the relevant cIAP1 ligand scaffold.

Researchers should validate specificity toward cIAP1 versus related IAPs (cIAP2, XIAP) using orthogonal assays (e.g., TR-FRET, fluorescence polarization, SPR) with the fully assembled bifunctional molecule.