Lanraplenib succinate - 10mM in DMSO , CAS No.1800047-00-0

CAS: 1800047-00-0 Cat. No.: L655296 Fórmula: C₂₃H₂₅N₉O.3/2C₄H₆O₄ Peso molecular: 620.64 Número EC: 873-961-4 PubChem CID: 133082362

CALIDAD & PUREZA 10mM in DMSO

Storage

Desiccated,Store at -80°C

Shipped In

Dry ice packs + Cold packs

Descripción general

Lanraplenib succinate (GS-9876 succinate) is a highly selective and orally active SYK inhibitor ( IC 50 =9.5 nM) in development for the treatment of inflammatory diseases. Lanraplenib succinate (GS-9876 succinate) inhibits SYK activity in platelets via the glycoprotein VI (GPVI) receptor without prolonging bleeding time (BT) in monkeys or humans

In Vitro

Lanraplenib succinate (GS-9876 succinate) inhibits anti-IgM stimulated phosphorylation of AKT, BLNK, BTK, ERK, MEK, and PKCδ in human B cells with EC 50 values of 24-51 nM. Lanraplenib monosuccinate inhibits anti-IgM mediated CD69 and CD86 expression on B-cells (EC 50 =112±10 nM and 164±15 nM, respectively) and anti-IgM /anti-CD40 co-stimulated B cell proliferation (EC 50 =108±55 nM). In human macrophages, Lanraplenib succinate inhibits IC-stimulated TNFα and IL-1β release (EC 50 =121±77 nM and 9±17 nM, respectively). Lanraplenib succinate (GS-9876 succinate) inhibits glycoprotein VI (GPVI)-induced phosphorylation of linker for activation of T cells and phospholipase Cγ2, platelet activation and aggregation in human whole blood, and platelet binding to collagen under arterial flow. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

IC50& Target:IC50: 9.5 nM (SYK)

Especificaciones

Especificaciones y pureza

10mM in DMSO

Mecanismos bioquímicos y fisiológicos

Lanraplenib succinate (GS-9876 succinate) is a highly selective and orally active SYK inhibitor ( IC 50 =9.5 nM) in development for the treatment of inflammatory diseases. Lanraplenib succinate (GS-9876 succinate) inhibits SYK activity in platelets via th

Condiciones de almacenamiento de almacenamiento

Desiccated,Store at -80°C

Enviado en

Dry ice packs + Cold packs

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Tipo de acción

INHIBITOR

Nombres e identificadores

Isómeros SMILES

C1CN(CCN1C2COC2)C3=CC=C(C=C3)NC4=NC(=CN5C4=NC=C5)C6=CN=CC(=N6)N.C1CN(CCN1C2COC2)C3=CC=C(C=C3)NC4=NC(=CN5C4=NC=C5)C6=CN=CC(=N6)N.C(CC(=O)O)C(=O)O.C(CC(=O)O)C(=O)O.C(CC(=O)O)C(=O)O

CAS alternativo

1800047-00-0

PubChem CID

133082362

Peso molecular

620.64

Application Protocols

Tested applications, recommended dilutions, and validated protocols are not provided for this product.

Not specified for this item; refer to CoA/Spec Sheet.

General non-validated handling guidance (for user optimization only)

• Stock preparation: Dissolve in anhydrous DMSO to 10–20 mM. Vortex and, if necessary, sonicate briefly. Confirm concentration by UV (if chromophore known) or by LC–MS against a calibration curve.
• Aliquoting: Dispense single-use aliquots (10–50 µL) into low-bind microtubes. Store at −80 °C under desiccation. Avoid repeated freeze–thaw.
• Assay dilution: Titrate over a broad range (e.g., 0.1 nM to 50 µM final) while maintaining constant vehicle concentration in controls. Include detergent (0.01% Tween 20) to reduce aggregation artifacts where appropriate.
• Plate handling: Use polypropylene plates for compound dilutions to minimize adsorption. Pre-wet tips with vehicle to improve transfer accuracy at low volumes.

Disclaimer: The above are generic good-practice suggestions and are not validated protocols for this specific item.

Biological Roles

Context (literature-based, non-clinical): Lanraplenib (free base) has been reported as a potent, ATP-competitive small-molecule modulator in immune signaling pathways, most notably associated with spleen tyrosine kinase (SYK) biology. The succinate salt presented here is a pharmaceutical-style counterion form commonly used to enhance solid-state properties and handling; it does not change the intrinsic target engagement of the neutral species.

General considerations for research use

• Pathway studies: SYK is a non-receptor tyrosine kinase involved in B-cell receptor signaling, Fc receptor signaling in myeloid cells, and downstream activation of pathways such as NF-κB and MAPK (literature). Small-molecule modulators are frequently used to dissect these cascades in biochemical and cellular assays.
• Phenotypic profiling: In cellular models, titration across several logs of concentration with appropriate vehicle controls enables separation of on-target effects from off-target or cytotoxic responses.
• Orthogonal validation: Combine chemical modulation with genetic perturbations (e.g., siRNA, CRISPR knockout) to strengthen causal inference in pathway assignments.

Best practices

• Confirm lot-specific identity and purity before biological testing (LC–MS/UPLC).
• Establish solubility and stability under assay conditions; maintain DMSO ≤0.1–0.5% v/v when possible.
• Include counter-screens (e.g., general kinase panels, reporter assays lacking the upstream kinase) to monitor selectivity.

Note: No medical, therapeutic, or diagnostic claims are made. Use strictly for laboratory research.

Buffer Applications

This product is not a buffering agent, and it is not typically used to prepare classical laboratory buffer systems.

Practical guidance for using in buffered assays

• Stock solutions: Prepare concentrated stocks in DMSO (e.g., 10–20 mM). Confirm full dissolution before dilution.
• Dilution into buffer: Add stock slowly to vigorously mixed buffer to prevent localized supersaturation. Maintain consistent final DMSO across controls and test wells.
• Buffer selection: Use assay-appropriate buffers (e.g., HEPES, Tris, phosphate). For salt-form compounds, mildly acidic buffers (pH 5.5–6.5) can help maintain protonation and solubility; basic buffers may drive conversion to the less soluble free base.
• Additives: A small amount of non-ionic surfactant (0.005–0.02% Tween 20 or Pluronic F-127) can minimize adsorption and aggregation in microplates and on plasticware.
• Filtration: If precipitation is observed after dilution, gently warm to room temperature and, if necessary, filter through 0.2 µm PVDF/PTFE. Reassess concentration by UV/LC–MS since filtration can cause loss.

Do not represent or use this compound as a pH buffer. Where buffering capacity is needed, rely on conventional systems (e.g., citrate pH 3–6, phosphate pH 6–8, Tris pH 7–9), and introduce the compound as a solute within the validated solvent tolerance of the assay.

Green Alternatives

As a bioactive library compound, lanraplenib succinate is not readily substituted. However, greener choices can be made in its handling and formulation, particularly in solvent selection and waste minimization.

Greener handling strategies

• Prefer DMSO over DMF/NMP where functionally equivalent; DMSO has a more favorable EHS profile and lower regulatory concern.
• Use aqueous buffers with minimal co-solvent when assay tolerance allows; employ pH adjustment to maintain solubility of the salt form.
• Implement microvolume dispensing (acoustic or pin tools) to reduce solvent consumption and waste.
• Consolidate analytical runs and use shorter LC gradients with aqueous mobile phases to reduce acetonitrile consumption.

Comparison of common vehicles (general)

• DMSO: High solvency; relatively green among polar aprotics; biodegradable; strong odor but low volatility.
• DMF/NMP: Powerful solvents but with higher reproductive toxicity concerns; avoid unless required.
• Ethanol/IPA: Renewable origin possible; higher volatility; assay tolerance varies.
• PEG 400: Low volatility and good solvency; may complicate bioassays due to viscosity but reduces VOC emissions.

Operational tips

• Design experiments to minimize repeated thawing and disposal of partially used aliquots—prepare just-in-time stocks.
• Segregate halogenated vs non-halogenated waste; most solutions of this compound in DMSO/buffer can go to non-halogenated organic waste streams, per institutional policy.

Trade-offs

• Lower-toxicity solvents may limit achievable concentration or stability; always confirm assay performance and compound integrity under the greener condition by LC–MS.

Pharmaceutical Uses

No clinical or therapeutic use is claimed or supported for this catalog item. It is provided strictly for laboratory research.

Formulation and developability context (general)

• Salt selection: Succinate is a commonly employed counterion in pharmaceutical development to improve crystallinity, processability, and sometimes dissolution rate. The salt form aids in handling and can reduce volatility of co-formulated solvents during processing.
• Pre-formulation screening: Researchers evaluating developability in early discovery may compare succinate with other salts (e.g., hydrochloride, mesylate, maleate) to optimize solid-state properties. Any salt exchange should be followed by thorough re-characterization (XRPD, DSC/TGA, Karl Fischer, NMR, LC–MS).
• Vehicle systems for in vivo method development (non-clinical research only): Typical vehicles include 10–20% PEG 400 + 2–5% ethanol + saline, or Captisol/cyclodextrin complexes; ensure ethical approvals and local regulations, and determine stability and dose linearity prior to use. Note: Aladdin provides no dosing guidance.

Analytical considerations

• Quantification in matrices often uses LC–MS/MS. Establish robust calibration in the intended vehicle/matrix and verify recovery and stability (bench-top, freeze–thaw, autosampler) as part of method development.

Regulatory note

• Not GMP, not pharmacopeial. For research only; not for human or veterinary use, household use, or as a food additive.

Physical Properties

Item-specific specifications

• Melting point, boiling point, density, refractive index, UV cutoff, water/peroxide/metal content: Not specified for this item; refer to CoA/Spec Sheet.
• Appearance: Not specified for this item; refer to CoA/Spec Sheet.

General/literature-based guidance for succinate salt forms of drug-like bases

• Physical state: Succinate salts commonly isolate as crystalline or microcrystalline solids; polymorphism and hydrates are possible and may affect dissolution and melting behavior.
• Solubility profile (typical):
  • Highly soluble in DMSO; stock solutions of 10–50 mM are commonly achievable for screening workflows.
  • Moderately soluble in polar aprotic solvents (DMF, NMP) and mixed aqueous/organic systems containing co-solvent (e.g., 10–50% v/v DMSO, 5–20% v/v ethanol or PEG 400).
  • Aqueous solubility may improve for the protonated form at acidic pH (pH 3–5) and diminish near neutral/basic pH if conversion to the free base occurs.
• LogP/logD: The free base of lanraplenib is reported in the literature to be lipophilic; the succinate salt increases apparent hydrophilicity in water but does not change intrinsic logP of the neutral species.
• pKa (qualitative): Presence of at least one basic nitrogen (protonable) is implied by salt formation; the succinate counterion has pKa1 ~4.2 and pKa2 ~5.6 (literature, for succinic acid) and does not reflect the base’s pKa.

Practical notes

• For quantitative solubility and purity, measure by HPLC/UPLC after preparing a test stock under your intended assay conditions.
• Control moisture; hygroscopic uptake can alter mass-based concentration calculations for salts.

Quality and Grades

Item-specific quality information

• Grade/purity: Not specified for this item; refer to CoA/Spec Sheet for assay purity, residual solvents, and analytical data (HPLC/UPLC, NMR, MS).

Interpreting common grades (general guidance)

• Research grade: Suitable for discovery research, screening, and non-GLP experiments; typically accompanied by analytical purity (e.g., HPLC area %) and identity confirmation (MS/NMR).
• Analytical/Chromatography grade solvents: Characterized for low UV absorbance and minimal non-volatile residues; pertinent when preparing reference solutions for LC/LC–MS assays.

Stabilizer and counterion considerations

• This product is a succinate salt. The counterion can impact crystallinity, hygroscopicity, and dissolution rate. If you require the free base or an alternative salt for specific experiments (e.g., permeability assays, crystallization trials), perform a controlled salt exchange and re-verify identity and purity.

Recommended quality controls (user-side)

• Identity: Confirm by LC–MS (m/z of free base), 1H/13C NMR (verify salt form and absence of major impurities), and, if possible, HRMS.
• Purity: Quantify by gradient UPLC with orthogonal detection (UV/Vis + MS). Assess for counterion stoichiometry and potential residual succinic acid.
• Stability screening: Short-term isothermal stability at 4 °C and ambient in sealed vials; light sensitivity check (cover with foil). Establish solution stability in your intended vehicle (e.g., DMSO at working concentration).

Reaction and Applications

This product is intended as a research small molecule for screening, target validation, and chemical biology workflows rather than as a synthetic reagent.

Applications (research use; no clinical use)

• Reference control in biochemical assays: Utilize as a positive or comparative control when profiling signaling pathways in enzyme or cell-based assays, ensuring concentration–response characterization and proper vehicle controls.
• Chemical probe development: Employ in orthogonal assays (biochemical, biophysical, phenotypic) to establish on-target versus off-target effects with matched inactive analogs.
• Selectivity profiling: Include in broad kinase or receptor panels to generate comparative selectivity maps (ensure appropriate assay windows and avoid aggregate-based inhibition; include detergent controls).
• Structural biology: Potential use in ligand-binding studies (e.g., thermal shift, SPR, MST) and, where feasible, co-crystallization/soaking with protein targets to inform structure–activity relationships. Confirm exact chemical structure and protonation state beforehand.

Practical tips

• Prepare concentrated DMSO stocks (10–50 mM), filter through 0.2 µm PTFE if particulates persist after dissolution.
• Include non-ionic surfactant (e.g., 0.01% Tween 20) in assay buffers to minimize nonspecific adsorption and aggregation artifacts.
• Verify solution stability across the assay timeframe (LC–MS check at t = 0 and end point). Avoid freeze–thaw by aliquoting single-use volumes.

Note: No reaction chemistry (e.g., coupling, reductions) is typically performed with this finished library compound; if derivatization is desired, convert to the free base and validate identity post-modification.

Reaction Conditions

No standard synthetic reaction conditions are associated with routine use of this material, as it is a finished research compound. The following notes apply only if performing ancillary operations such as salt exchange or formulation-relevant processing.

Salt exchange (general guidance)

• Liberation of free base: Dissolve the succinate salt in minimal water/MeOH, basify carefully (e.g., NaHCO3/Na2CO3 to pH ~9–10), and extract the free base into an immiscible organic solvent (e.g., MTBE/EtOAc). Dry (Na2SO4) and evaporate under reduced pressure at ≤30–35 °C.
• Formation of alternate salt: Dissolve/free-base in anhydrous solvent (EtOAc/IPA/acetone) and add a stoichiometric amount of the chosen acid (e.g., HCl in IPA/ether, methanesulfonic acid, maleic acid) under cooling. Seed if needed to induce crystallization. Isolate and dry under vacuum. Validate by NMR/XRPD.

Solution preparation for bioassays

• Solvent: DMSO is preferred; typical stock concentrations 10–50 mM (verify solubility and stability by LC–MS).
• Temperature: Room temperature dissolution; gentle warming (≤37 °C) can help dissolve without degradation.
• Light: Protect from strong light if aromatic; store aliquots in amber vials.

Stability checks

• Perform short-term (24–72 h) stability assessments in intended media at assay temperature. Monitor by LC–MS for degradation or adsorption losses.

Note: The above are general, literature-style practices; optimize locally and confirm against analytical data. They are not item-specific specifications.

Safety and Handling

Authoritative safety information resides in the Safety Data Sheet (SDS). The following is general guidance for small-molecule research compounds and organic salts.

Item-specific storage and shipping

• Storage: Desiccated, Store at −80 °C (as provided in Product Data).
• Shipping: Dry ice packs + Cold packs (as provided in Product Data).

GHS/SDS information

• Signal word, H-statements, pictograms, and classification: Not specified for this item; consult the SDS.

General laboratory precautions

• PPE: Wear lab coat, safety glasses, and appropriate chemical-resistant gloves (e.g., nitrile). Handle powders in a fume hood to minimize inhalation of dust/aerosols.
• Avoid ingestion, inhalation, and skin/eye contact. Wash thoroughly after handling.
• Incompatibilities: Strong oxidizers and strong acids/bases may degrade sensitive heterocycles or alter the salt state. Avoid prolonged exposure to moisture (hydrates) and elevated temperatures.
• First aid (general):
  • Skin/eye contact: Rinse with copious water for at least 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.
• Spill response: Avoid dust generation. Collect with inert absorbent, place in suitable container for disposal according to institutional and local regulations.

Special risks and handling tips

• Many kinase-targeted research compounds are bioactive at low concentrations. Minimize exposure and practice good containment (closed tubes, wipedown procedures).
• Prepare solutions fresh where possible; aliquot to avoid repeated freeze–thaw cycles that may induce degradation.

Solvent Selection

Compound class: non-volatile, drug-like organic salt (succinate). Solvent choice should balance solubility, stability, and the needs of the intended bioassay or analytical method.

General miscibility and polarity guidance (literature-based)

• Primary stock solvent: DMSO (high solvating power for heteroaromatic bases; compatible with most screening assays at ≤0.5% v/v final).
• Alternative polar aprotic solvents: DMF, NMP (useful for intermediate concentrates; assess cytotoxicity in cellular assays).
• Co-solvent systems: Water with 5–50% DMSO or 5–20% ethanol/PEG 400 can improve delivery into aqueous buffers.
• Aqueous buffers: Acidified buffers (e.g., citrate/phosphate at pH 4–6) may maintain the protonated form and enhance apparent solubility; basic buffers can favor precipitation of the free base.

Selection tips

• For enzyme/cell assays: Prepare a DMSO master stock (e.g., 10–20 mM), then serially dilute into assay buffer, keeping final DMSO ≤0.1–0.5% where possible.
• For permeability/transport studies: Consider preparing both salt and free-base solutions to study pH-dependent behavior; adjust pH carefully and verify by LC–MS.
• For NMR: DMSO-d6 or CD3OD typically give good spectra; addition of a drop of D2O can help assign succinate resonances if present as a separate species.

Quick comparison

• DMSO: maximal solubility and stability; broadly compatible.
• Ethanol: convenient but limited by volatility and assay tolerance.
• PEG 400: low volatility, good solubilizer; may affect viscosity and assay readouts.
• Aqueous buffer alone: often insufficient unless pH is adjusted to keep the compound protonated.

Storage and Reconstitution

Item-specific conditions

• Storage: Desiccated, Store at −80 °C (per Product Data). Protect from moisture; keep container tightly closed.
• Shipping: Dry ice packs + Cold packs (per Product Data). Inspect packaging upon receipt; return to −80 °C promptly.

Reconstitution (general guidance for small-molecule salts)

• Solvent: Use anhydrous DMSO for primary stocks. Typical concentrations: 10–50 mM, subject to actual solubility. If lower concentrations are required, prepare serial dilutions in DMSO or assay-compatible co-solvent systems.
• Procedure: Allow vial to equilibrate to room temperature in a desiccator before opening to prevent condensation. Weigh quickly, cap promptly. Add solvent in one portion, vortex to clarity; brief sonication may assist. If particulates remain, gently warm (≤37 °C) and/or filter through 0.2 µm PTFE.
• Aliquoting: Prepare single-use aliquots to avoid freeze–thaw. Store aliquots in amber or foil-wrapped vials if light sensitivity is suspected.

Stability and handling

• Working solutions in aqueous buffers should be prepared fresh. Assess stability by LC–MS under intended assay conditions.
• Avoid prolonged exposure to ambient humidity; succinate salts may be hygroscopic.
• Disposal: Follow institutional guidelines for organic chemical waste.

Specifications not provided

• Exact solubility limits, appearance, and shelf-life: Not specified for this item; refer to CoA/Spec Sheet and SDS for authoritative guidance.

Structure and Identity

Lanraplenib succinate is supplied as the succinate salt of the small-molecule research compound lanraplenib.

Item-specific identifiers

• SKU: L655296 (Aladdin Scientific)
• Product name: Lanraplenib succinate
• CAS: 1800047-00-0 (succinate salt; literature identifier)
• PubChem CID: 133082362 (literature identifier for lanraplenib succinate)

Chemical descriptors

• 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)

• Compound type: Organic salt consisting of a protonated basic small molecule (lanraplenib) paired with the dicarboxylate counterion succinate.
• Functional groups (generic): Typically includes heteroaromatic/aryl motifs and at least one basic nitrogen capable of salt formation; the succinate counterion bears two carboxylates (–OOC–CH2–CH2–COO–).
• 2D description in words: A cationic drug-like framework (lanraplenib) balanced by a dianionic succinate; overall presented as a neutral salt complex in the solid state.

Notes

• The exact stereochemistry and atom-level connectivity for lanraplenib succinate should be confirmed against the certificate of analysis (CoA) or an authoritative structure database before structure-based work (e.g., docking, crystallography).

Synthetic Utility

Lanraplenib succinate is a finished small-molecule salt intended for biological and analytical studies, not as a general-purpose synthetic reagent or building block.

Potential chemist-facing utilities (limited)

• Salt metathesis: Conversion between salt forms (e.g., succinate to free base or other pharmaceutically acceptable salts) can be used to tune solid-state properties for method development. Typical approach involves basification to liberate the free base, extraction into an organic phase, and re-protonation with the desired acid under controlled conditions.
• Analytical standards: Can serve as a reference standard for LC–MS method development (retention, ionization), stability-indicating methods, and impurity profiling. Confirm exact counterion stoichiometry before quantitative use.
• Derivatization (advanced): If SAR expansion or tagging is intended, first confirm the structure and functional handles on the free base. Protecting-group strategies and mild conditions are favored to preserve heteroaromatic integrity.

Not typically suitable for

• Acting as a nucleophilic/electrophilic reagent in classical transformations (e.g., cross-coupling feedstock, organometallic reactions) without prior deconstruction or functionalization.

Good practices

• After any chemical manipulation (salt exchange, derivatization), re-establish identity/purity by orthogonal methods (NMR, HRMS, UPLC) and assess residual counterions (succinic acid) and solvent levels.

Target Specificity

Item-specific target information (antigen/epitope/clone/species) is not applicable to small molecules and is not provided for this product.

• Target, potency, and selectivity data: Not specified for this item; refer to primary literature and your internal assay data for target engagement profiles relevant to your research context.

Note: While the free base lanraplenib has literature reports concerning kinase pathway modulation, Aladdin provides no validated target specificity data for this specific catalog lot. Users should independently confirm potency and selectivity in their own systems.

Preguntas frecuentes

How should this product be stored?

Store at ?80 °C, desiccated. Keep the container tightly closed with desiccant — the material is moisture-sensitive.

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 1800047-00-0, the molecular formula is C23H25N9O.3/2C4H6O4, and the molecular weight is 620.64 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.