Pelacarsen , CAS No.1637637-70-7

CAS: 1637637-70-7 Cat. No.: P1440449 Molecular Weight: 8636.00

Storage

Store at -20°C,Desiccated

Shipped In

Ice chest + Ice pads

Overview

Pelacarsen (AKCEA-APO(a)-LRx) is a liver-specific antisense oligonucleotide against apolipoprotein (a) that reduces lipoprotein(a) up to 80% with good tolerability.

Specifications

Storage

Store at -20°C,Desiccated

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

8636.00

Application Protocols

Item-specific, tested application protocols are not provided in the Product Data.

• Recommended applications, doses, and incubation times: Not specified for this item; refer to CoA/Spec Sheet.
• Positive controls/validation assays: Not specified for this item; refer to CoA/Spec Sheet.

General literature considerations for ASO use (for planning only, not item-specific instructions):

• In vitro: Prepare nuclease-free stock (e.g., 100–1000 µM), dilute into cell culture medium to desired nominal concentration, and include scrambled/mismatch controls. Gymnotic uptake can occur in some cell types; others may require delivery reagents compatible with ASOs.
• In vivo (research): Formulate in sterile isotonic buffer at neutral pH and follow institution-approved protocols. Determine dose and schedule empirically based on target biology and observed durability.

Always consult the product’s CoA/Spec Sheet and SDS for any item-specific instructions and restrictions.

Biological Roles

Research context (literature/general):

• Modality: Pelacarsen is described in the literature as a chemically modified antisense oligonucleotide designed to hybridize to a specific RNA transcript, enabling RNase H1-mediated target RNA degradation within the nucleus or cytosol.
• Delivery biology: Triantennary N-acetylgalactosamine (GalNAc) conjugation is widely used to promote high-affinity binding to the asialoglycoprotein receptor (ASGPR) on hepatocytes, enabling efficient uptake and liver-selective distribution in research models.
• Pathway interrogation: Such ASOs enable targeted reduction of gene expression to probe functional roles in lipid metabolism, inflammatory signaling, or other hepatic pathways. In published work, pelacarsen has been associated with studies of apolipoprotein(a) (LPA) biology and lipoprotein(a) assembly (literature), facilitating mechanistic experiments on gene–phenotype relationships.
• Kinetics/durability: Chemically stabilized ASOs often exhibit prolonged tissue residency and sustained target engagement in vivo (literature), allowing spaced dosing in animal studies and extended observation windows for downstream proteomic or metabolomic effects.
• Off-target considerations: Sequence-dependent hybridization means that partial complementarity to unintended RNAs can yield secondary effects; bioinformatic screening and appropriate control oligos are essential for rigorous interpretation.

No medical or clinical claims are made here. This product is offered strictly for research use.

Buffer Applications

Pelacarsen, as an ASO, is typically handled in aqueous buffers. Item-specific buffer requirements are not provided; the following are general, literature-based practices for oligonucleotides.

Common buffer systems (literature/general):

• Nuclease-free water: Ideal for stock preparation and maximum compatibility. Adjust pH to ~7.0–8.0 if needed with nuclease-free reagents.
• PBS (1×, pH 7.2–7.4): Isotonic; suitable for cell work and in vivo preparations where saline tonicity is required.
• HEPES-buffered saline (20–25 mM HEPES, 150 mM NaCl, pH 7.4): Excellent pH control without phosphate interference.
• TE buffer (10 mM Tris, 0.1–1 mM EDTA, pH 7.5–8.0): EDTA chelates divalent cations, reducing nuclease activity and improving solution stability for storage aliquots.

Practical notes:

• Filtration: If sterility is required, pass through a 0.22 µm low-protein-binding filter. Avoid cellulose acetate if adsorption is problematic; PVDF or PES low-binding membranes are common.
• Adsorption mitigation: Add inert carrier protein (e.g., 0.1 mg/mL HSA) or polysorbate 20 (≤0.01%) where permitted to limit surface losses in very dilute solutions.
• pH/ionic strength: Maintain neutral pH; typical ionic strength 100–150 mM NaCl improves robustness in handling and reduces nonspecific interactions.

Note: Specific buffer composition, sequence-dependent stability, and concentration for this item are not specified; consult the CoA/Spec Sheet and adapt to your assay’s requirements.

Green Alternatives

Context: Pelacarsen is an aqueous-handled oligonucleotide. Green chemistry considerations focus on minimizing hazardous solvents and waste during handling and formulation work rather than replacing a reaction solvent.

Greener handling strategies (literature/general):

• Prefer water-based systems: Use nuclease-free water or buffered saline in place of organic co-solvents whenever possible.
• Avoid chlorinated solvents: ASOs are not soluble in such media; eliminating them reduces environmental impact with no performance penalty.
• Concentrated stocks: Prepare higher-concentration stocks to reduce packaging and cold-chain shipping mass (institutional policy permitting).
• Single-use plastics reduction: Employ low-binding, reusable glassware where compatibility and sterility allow; otherwise choose certified low-binding consumables to reduce waste from repeated trial preparations.

Comparison (general):

• Aqueous buffer (PBS/HEPES/TE): High EHS profile favorability; low VOC, minimal flammability; excellent ASO compatibility.
• Alcohol–water mixtures: Potentially useful for certain formulations but increase VOC footprint and may affect biological assays; use only when justified by data.

Trade-offs:

• Strict nuclease-free practices may increase use of disposable plastics; balance with validated cleaning/sterilization protocols for reusables where practical.

Bottom line: For ASO work, water-based buffers are generally the most sustainable and experimentally appropriate medium.

Pharmaceutical Uses

No therapeutic or clinical claims are made. The following information reflects general formulation research considerations for antisense oligonucleotides (ASOs) and GalNAc–ASOs; no item-specific regulatory status is provided.

Formulation research context (literature/general):

• Route/platform: GalNAc-conjugated ASOs are commonly explored for subcutaneous administration in preclinical research due to hepatocyte targeting via ASGPR.
• Excipients: Simple isotonic saline or buffered saline is frequently sufficient. Stabilizers can include sugars (e.g., sucrose, trehalose) and surfactants at very low levels to minimize interfacial losses; compatibility must be empirically verified.
• Concentration and tonicity: Adjust NaCl or use PBS to maintain osmolality; maintain pH ~7.2–7.4 for parenteral-like research preparations.
• Container–closure: Low-binding plastics or Type I glass vials with appropriate stoppers reduce adsorption; siliconization and surfactants can have opposing effects on interfacial behavior.
• Quality attributes of interest: Identity, purity, potency (by A260 or HPLC), particulate matter, pH, osmolality, bioburden/endotoxin (as applicable for in vivo research), and stability indicating methods.

Regulatory note: Pharmacopeial monographs typically do not exist for specific ASOs; any GMP status, pharmacopeial alignment, or clinical suitability is not specified for this item. This material is provided strictly for research use.

Physical Properties

Item-specific physical data:

• Appearance: Not specified for this item; refer to CoA/Spec Sheet.
• Molecular weight: Not specified for this item; refer to CoA/Spec Sheet.
• Density, MP/BP, refractive index, UV cutoff: Not specified for this item; refer to CoA/Spec Sheet.

Literature/general characteristics for antisense oligonucleotides (ASOs):

• State: Typically provided as a lyophilized solid or dried film; highly hygroscopic and polyanionic. Exact form for this item is not specified.
• Solubility: Freely soluble in nuclease-free water and physiological buffers (e.g., PBS, HEPES, Tris) at common working concentrations (e.g., 10–1000 µM). Poorly soluble in nonpolar organic solvents.
• pKa/logP: Classical pKa/logP are not directly meaningful due to the multianionic phosphate/phosphorothioate backbone; the oligonucleotide behaves as a water-soluble polyelectrolyte (literature).
• UV absorbance: Strong absorption near 260 nm typical for nucleic acids; extinction coefficient is sequence-dependent (literature; item-specific ε not specified).
• Thermal behavior: Lyophilized ASOs are generally stable at −20 °C under desiccation and protected from light; in solution, stability depends on buffer, pH (neutral), nuclease contamination, and storage temperature (literature guidance only).

Note: For any precise specification (e.g., exact MW, counterion, residual solvent, moisture content), consult the item’s CoA/Specification Sheet.

Quality & Grades

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

How to interpret oligonucleotide quality (general guidance):

• Purity metrics: Reported as % full-length by HPLC/UPLC and/or CE. Identity confirmation by LC–MS or high-resolution MS is common. Sequence integrity may be supported by enzymatic digestion mapping.
• Counterion/form: Sodium salt vs free acid, and hydration state can influence concentration calculations and mass. The specific salt/form for this item is not specified.
• Residuals/impurities: Potential residuals include small-molecule protecting groups, solvents, salts, truncated sequences (n−1), and linker-related species. Acceptance criteria are item- and supplier-specific.
• UV potency: Extinction coefficient (ε260) is sequence-dependent; accurate quantification requires sequence-specific ε or supplier-provided A260-to-concentration conversion.
• Stabilizers: ASOs are typically supplied without stabilizers; some may include volatile buffers or minimal salts. No stabilizer information is provided for this item.

Practical notes:

• Always verify on the CoA: exact sequence (if disclosed), length, conjugation (e.g., GalNAc), counterion, purity percentage, and recommended quantification method.
• For sensitive applications (e.g., in vivo or advanced cell studies), request documentation on endotoxin/bioburden, nuclease testing, and residual solvent/metals, if relevant.

Reaction & Applications

This product is not a small-molecule reagent for synthetic transformations; it is an antisense oligonucleotide intended for biological research workflows.

Research application context (literature/general):

• Mechanism: Antisense gapmers typically bind complementary RNA and elicit RNase H1-mediated cleavage of the RNA strand within RNA:DNA hybrids. Chemical modifications and conjugation are used to enhance stability, affinity, and delivery.
• Use cases: Gene expression knockdown studies, pathway validation, target engagement benchmarking, and hepatocyte-targeted delivery investigations when GalNAc conjugation is present.
• Controls: Include scrambled-sequence controls, mismatch controls, and dose–response series to establish sequence-specific effects and minimize off-target interpretations.
• Quantification of effect: RT-qPCR for target mRNA levels, digital PCR, and downstream protein analyses (e.g., immunoblotting, proteomics) are commonly employed. For hepatocyte models, uptake can be confirmed by fluorescently labeled surrogate oligos or hybridization-based assays.

Practical tips (literature):

• Work RNase-free—use certified nuclease-free water and consumables; wear gloves and change them frequently.
• Adsorption: Pre-wet plasticware with buffer or add carrier (e.g., 0.1 mg/mL HSA) if nonspecific binding is problematic in dilute solutions.
• Dose preparation: Prepare concentrated stocks (e.g., 100–1000 µM) to minimize freeze–thaw and dilution errors; filter sterilize (0.22 µm) if sterility is required and the oligo is compatible.

Reaction Conditions

Not typically applicable. Pelacarsen is not used as a reagent for organic reactions; therefore, conventional parameters such as catalysts, temperatures, or yields are not relevant.

Literature/general handling conditions for ASO use in biology:

• Solution preparation: Dissolve in nuclease-free water or buffer at neutral pH. Gentle mixing at room temperature is adequate; avoid vigorous vortexing that can introduce foaming and adsorption losses.
• Sterility: For cell or in vivo research, sterile filtration (0.22 µm) may be employed if compatible.
• Working temperatures: Prepare and handle on ice for extended manipulations; incubations in biological assays follow model-specific protocols (e.g., 37 °C for cell culture exposure), not chemical reaction conditions.

For any operational parameters specific to this item (e.g., recommended stock concentration, buffer system, or compatibility notes), consult the product CoA/Spec Sheet.

Safety & Handling

Regulatory/SDS:

• GHS classification, signal word, hazard statements, and pictograms: Not specified for this item; refer to SDS for authoritative safety information.

General laboratory safety for oligonucleotides (literature/practice):

• Expected hazards: Low volatility, not flammable, not a strong oxidizer/reducer. Primary risks arise from particulate/dust exposure and potential sensitization.
• PPE: Use standard lab PPE—lab coat, safety glasses, and disposable nitrile gloves. Avoid generating dust/aerosols. Handle solutions using RNase/DNase-free technique to avoid degradation and inadvertent exposure.
• Engineering controls: Work on a clean bench; for weighing, consider a fume hood or containment to minimize dust. Use dedicated nuclease-free consumables.
• Incompatibilities: Avoid strong acids/bases that may depurinate or cleave the backbone; avoid nucleases (biological contamination), and prolonged exposure to elevated temperatures.
• First aid (overview; consult SDS): If inhaled, move to fresh air; if on skin/eyes, rinse with water. If ingested, rinse mouth and seek medical attention. Provide SDS to healthcare professionals.
• Spill/cleanup: For solids, carefully sweep with minimal dust generation; for solutions, wipe with absorbent and decontaminate surface. Dispose of according to institutional and local regulations for laboratory chemical/biological waste.

Research use: For research use only. Not for human or veterinary use.

Solvent Selection

Applicability: Pelacarsen is an oligonucleotide material; solvent choice focuses on aqueous, nuclease-free systems rather than organic reaction media.

General solvent guidance (literature/practice):

• Primary solvents: Nuclease-free water (RNase/DNase-free) for stock solutions. Common buffers include PBS (pH 7.2–7.4), HEPES (pH 7.4), and Tris/EDTA (TE, pH 7.5–8.0). EDTA helps chelate divalent cations that can accelerate nuclease activity.
• Ionic strength: 50–150 mM monovalent salts (Na+, K+) maintain oligo integrity and minimize nonspecific adsorption; avoid high Mg2+/Ca2+ unless required for downstream biology.
• Co-solvents: If needed for formulation screening, low percentages of sterile-filtered ethanol or isopropanol can be explored; however, purely aqueous systems are preferred. Avoid nonpolar solvents; ASOs are not soluble and may denature.
• pH window: Neutral pH (≈7.0–8.0) is generally optimal to maintain backbone and base integrity.

When to choose alternatives:

• For transfection-free delivery to hepatocyte-derived systems, GalNAc-conjugated ASOs are typically used neat in buffer; for non-hepatic cells, lipid-based carriers or gymnotic uptake media can be evaluated (methodological choice, not a solvent substitution).

Comparison snapshot (literature):

• Water vs PBS: Water maximizes chemical simplicity; PBS adds isotonicity and reduces adsorption to plastics. TE adds nuclease protection via EDTA chelation.

Storage & Reconstitution

Item-specific conditions from Product Data:

• Storage: Store at −20 °C, desiccated.
• Shipping: Ice chest + ice pads.

General reconstitution and handling (literature/practice; not item-specific specifications):

• Reconstitution solvent: Use nuclease-free water or buffer (e.g., PBS, HEPES, or TE at pH ~7.2–7.8). Mix gently by inversion; avoid vigorous vortexing or frothing.
• Stock concentration: Choose a convenient high concentration (e.g., 100–1000 µM) to minimize freeze–thaw cycles and adsorption. Actual concentration for this item is not specified; calculate from CoA-provided mass and MW if supplied.
• Aliquoting: Dispense into single-use, low-binding tubes to avoid repeated freeze–thaw. Maintain aseptic, RNase-free technique.
• Storage of solutions: Short term (≤1–2 weeks) at 2–8 °C; longer term at −20 to −80 °C. Protect from light and moisture. Stability is sequence- and buffer-dependent; verify empirically.
• Avoid contaminants: Use RNase/DNase-free consumables; include 0.1–1 mM EDTA in storage buffers to chelate divalent cations and reduce nuclease activity if compatible with downstream assays.
• Thawing: Thaw on ice, mix gently, quick spin to collect condensate, and keep cold during setup. Do not refreeze partially used aliquots.

Note: If the CoA provides specific reconstitution buffer, concentration, or additional stabilizers for this item, follow those instructions preferentially.

Structure & Identity

Brief overview: Pelacarsen is supplied as a research-use-only antisense oligonucleotide (ASO) material. Item-specific structural identifiers are not provided in the Product Data.

• SKU: P1440449
• Product name: Pelacarsen
• CAS: 1637637-70-7
• 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.
• Synonyms (literature/general): also referenced as IONIS-APO(a)-LRx, TQJ230 (literature).

Structural features (literature/general):

• Antisense oligonucleotide (ASO) bearing a polyanionic phosphate/phosphorothioate backbone with nucleobase sequence designed to engage a complementary RNA target.
• GalNAc (N-acetylgalactosamine) ligand conjugation via a triantennary cluster and linker is commonly used in “LRx” ASOs to enhance hepatocyte uptake via ASGPR (literature; not specified for this supplied item).
• Typical ASO “gapmer” architecture includes 2′-modified ribose residues in the wings (e.g., 2′-O-methoxyethyl, 2′-O-methyl) flanking a DNA gap to recruit RNase H1 (literature; sequence/chemistry not specified for this item).

2D structure description (literature/general):

• A linear oligomer comprised of repeating sugar–phosphate units bearing heterocyclic nucleobases; where present, a triantennary GalNAc cluster is appended through a linker at or near the 5′-end to a phosphorothioate backbone. Exact sequence/positions are product-specific and are not provided for this item.

Synthetic Utility

This product is not a general-purpose small-molecule building block or reagent; it is an antisense oligonucleotide intended for biological research. As such, it is not typically used as a substrate, catalyst, or intermediate in chemical synthesis.

General chemistry context (literature/general):

• Oligonucleotide conjugates like GalNAc–ASOs embody multiple functional motifs (polyanionic backbone, heterocyclic nucleobases, carbohydrate ligands), but these features are optimized for nucleic acid hybridization and biological delivery rather than for carrying out chemical transformations.
• If chemical modification is required in a research setting (e.g., fluorescent labeling, biotinylation), it is generally performed on dedicated, prefunctionalized oligos or via solid-phase synthesis rather than post-synthetic modification of a finished, sequence-defined ASO.

Recommendation: For synthetic applications, select appropriate small-molecule reagents or protected nucleoside phosphoramidites. Use this product where sequence-specific RNA recognition is the objective.

Target Specificity

Item-specific target information (gene, transcript, binding site, species cross-reactivity) is not provided in the Product Data.

• Target, epitope, binding site: Not specified for this item; refer to CoA/Spec Sheet.
• Species/application validation: Not specified for this item; refer to CoA/Spec Sheet.

General literature note: Pelacarsen has been described in publications as an antisense oligonucleotide designed to modulate expression of apolipoprotein(a) by targeting LPA mRNA; however, no target details are specified for this supplied item. Users should verify target sequence and species suitability for their experiments.

Frequently Asked Questions

How should this product be stored?

Store at ?20 °C, desiccated. Keep the container tightly closed with desiccant — the material is moisture-sensitive.

How is this product shipped?

This product ships in an insulated container with ice pads. Unpack on arrival and transfer it to the storage condition stated above.

What are the CAS number, molecular formula and molecular weight?

The CAS Number is 1637637-70-7, and the molecular weight is 8636.00 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.