GSK3494245 - 10mM in DMSO , CAS No.2080410-41-7

CAS: 2080410-41-7 Cat. No.: G656818 Formula: C₂₁H₂₃FN₆O₂ Peso molecolare: 410.44 PubChem CID: 126571915

GRADE & PURITY 10mM in DMSO

Storage

Store at -80°C

Shipped In

Dry ice packs + Cold packs

Panoramica

GSK3494245 (DDD01305143) is a potent, orally active, and selective inhibitor of the chymotrypsin-like activity of the parasite proteasome binding in a site sandwiched between the β4 and β5 subunits ( IC 50 =0.16 μM for WT L. donovani proteasomes). GSK3494245 moderately inhibits chymotrypsin-like activity of human proteasome (IC 50 : purified 26S=13 µM; enriched THP-1 extracts IC 50 =40µM). GSK3494245 exhibits attractive biological and biosafety properties.

In Vitro

GSK3494245 shows EC 50 value of 5.7 μM in L. donovani intramacrophage assay, where the amastigotes are cultured in differentiated THP-1 cells. GSK3494245 demonstrates good selectivity over mammalian cell growth inhibition (THP-1 cells; EC 50 > 50 μM). GSK3494245 (DDD01305143) shows pEC 50 s of 6.5 and 5.8 against axenic amastigote and ld InMac, respectively. Ld InMac is the intramacrophage assay carried out in THP-1 cells with L. donovani amastigote. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

In Vivo

GSK3494245 (25 mg/kg; orally twice a day for 10 consecutive days) elicits a >95% reduction of parasite load in Infected mice ( L. donovani , LV9) . MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Specifications

Specifiche e purezza

10mM in DMSO

Meccanismi biochimici e fisiologici

GSK3494245 (DDD01305143) is a potent, orally active, and selective inhibitor of the chymotrypsin-like activity of the parasite proteasome binding in a site sandwiched between the β4 and β5 subunits ( IC 50 =0.16 μM for WT L. donovani proteasomes). GSK3494

Condizioni di conservazione di stoccaggio

Store at -80°C

Spedito in

Dry ice packs + Cold packs

Questo prodotto richiede spedizione a catena fredda. I servizi di terra e altri servizi economici non sono disponibili.

Tipo di azione

INHIBITOR

Nomi e identificatori

Isomeri SMILES

C1CCN(C1)C(=O)NC2=CC(=C(C=C2)F)C3=NC4=NC=C(N4C=C3)N5CCOCC5

PubChem CID

126571915

Peso molecolare

410.44

Application Protocols

No tested applications or protocol recommendations are provided for this product in the catalog entry.

General guidance for small-molecule screening compounds (not item-specific):

• Stock preparation: If provided as a solid, weigh quickly at ambient temperature to limit moisture uptake, then dissolve in anhydrous DMSO to a convenient master concentration (e.g., 10–50 mM). Filter (0.22 µm PTFE) if particulate persists.
• Plate handling: Use low-bind plates; maintain consistent DMSO across wells; include vehicle controls.
• Assay validation: Run a dilution series to establish dynamic range and check for precipitation or turbidity at working concentrations.
• Analytical QC: Confirm identity by HRMS and purity by LC-UV/ELSD before critical studies. For quantitative biology, consider absolute concentration verification by qNMR.

Because no specific WB/IHC/IF/FC or enzymatic assay conditions are provided, users should adapt their laboratory’s validated SOPs and consult primary literature relevant to the compound’s CAS/CID.

Biological Roles

No mechanism-of-action or target annotations are provided in this listing for GSK3494245. The following guidance reflects general practice for research-use small molecules and should not be interpreted as therapeutic claims.

• Intended context: Chemical biology, target validation, and assay development in discovery settings. This product is for research use only.
• Target specificity: Not specified for this item; refer to primary literature associated with CAS 2080410-41-7 or PubChem CID 126571915, and confirm against the supplied lot documentation.
• Use as a reference material: Compounds with proprietary or code names are often employed as internal controls or benchmarks in biochemical or cellular assays. Verify potency ranges and assay conditions from peer-reviewed sources before use.
• Off-target considerations (general): When profile data are unavailable, employ orthogonal assays and counterscreens to detect pan-assay interference (PAINS), redox activity, aggregation, or fluorescence/absorbance artifacts.
• ADME/PK (general cautions): Do not infer solubility, permeability, or stability. If needed, generate preliminary data (e.g., kinetic solubility, microsomal stability, PAMPA/Caco-2) under your laboratory’s validated protocols.

Documentation: Archive any literature MOA or target attributions together with the exact lot identifiers to avoid misannotation, as code-named compounds can have multiple forms (free base/salt, stereoisomers) in circulation.

Buffer Applications

This product is a small-molecule screening compound and is not a buffering agent. Therefore, classical buffer system guidance (pKa-based selection, ionic strength, capacity) is not directly applicable.

Practical notes for assay buffers (general, not item-specific):

• When diluting DMSO stock solutions into assay buffers (e.g., PBS, HEPES, Tris), maintain consistent final DMSO content across wells (commonly 0.1–0.5% v/v) to control solvent effects.
• Include solubilizing excipients when assay-appropriate (e.g., 0.01–0.05% Tween 80, 0.1% BSA) to mitigate precipitation and nonspecific binding.
• Filter buffers (0.22 µm) and equilibrate to assay temperature to improve reproducibility.

If the compound itself exhibits acid/base functionality and buffer-dependent activity (unknown here), perform a small pH–activity/solubility screen (e.g., pH 6.0–8.0) to identify optimal working conditions.

Green Alternatives

Green chemistry comparisons typically concern solvent or reagent choices. As GSK3494245 is supplied as a research-use screening compound rather than a process reagent or solvent, “greener alternative” selection is generally not applicable to the compound itself.

Practical green considerations for using this item (general, not item-specific):

• Prefer greener dissolution media where feasible (e.g., ethanol or aqueous co-solvent systems) while acknowledging that DMSO often remains necessary for lipophilic discovery compounds.
• Minimize solvent volumes by preparing concentrated master stocks and performing accurate serial dilutions to reduce waste.
• Use miniaturized assay formats (384/1536-well) to decrease per-experiment solvent and compound consumption.
• Consolidate shipments (this product ships on dry ice + cold packs) to reduce cold-chain footprint and packaging waste.

If a substitute compound with similar biological profile is being considered for greener manufacturing or handling reasons, conduct a comparative assessment using tools like the ACS GCI Pharmaceutical Roundtable solvent/auxiliary guides and GreenScreen, recognizing that such assessments require full structural and hazard information not provided in this listing.

Pharmaceutical Uses

No excipient role, compendial status, or formulation specifications are provided for GSK3494245 in this listing. This product is supplied strictly for research use only and is not intended for human or veterinary use.

Research/formulation-related uses (general, not item-specific):

• Reference standard: May be employed as an analytical reference in method development (e.g., LC-MS/MS quantitation in matrices) once identity and purity are confirmed by CoA.
• Preformulation screening: If structure and purity are verified, investigators may assess solubility, stability (pH/light), and compatibility with common vehicles (e.g., PEG 400, Captisol, aqueous buffers with co-solvent) for non-clinical research.
• Salt/form selection studies: Where applicable, counterion screening and polymorph assessments can be conducted to support physicochemical optimization; none of this is specified for the current item.

Compliance note: Do not use this material for diagnostic, therapeutic, or in vivo clinical applications. Any mention of potential pharmacological classes in external literature must be independently verified and does not alter the research-use-only status of this product.

Physical Properties

Item-specific physicochemical data are not provided in this listing. Do not assume values; verify against the lot-specific CoA or SDS.

• 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 (literature/general): Not available in this listing; consult primary databases using CAS 2080410-41-7 or CID 126571915 and confirm for the exact lot and form.
• Boiling point (literature/general): Typically not applicable for high-MW, nonvolatile bioactive small molecules; specific value not provided here.
• Density, refractive index, logP/logD, pKa, UV-Vis λmax, water content: Not specified for this item; refer to CoA/Spec Sheet.
• Solubility: Not specified for this item; refer to CoA/Spec Sheet. As a general practice for discovery compounds, initial dissolution is often screened in anhydrous DMSO (analytical grade) before dilution into assay media.

Practical notes (general, not item-specific):

• If the compound is provided as a solid, determine solubility by preparing a small solubility screen (e.g., DMSO, DMF, ethanol, aqueous buffers with co-solvent) and verify by visual inspection and analytical HPLC.
• If the compound is provided as a DMSO solution, confirm concentration by UV-Vis only when an extinction coefficient is known; otherwise, quantify by quantitative NMR or LC-UV with a calibrated standard.

Quality and Grades

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

Interpretation and expectations (general for small-molecule screening items):

• Research-use screening quality typically emphasizes structural confirmation (e.g., 1H NMR/HRMS) and chromatographic purity (HPLC/UPLC, area% basis). If purity is critical for SAR or in vivo exploratory work, request a current CoA and consider independent verification.
• HPLC/UPLC purity: Confirm the detector type (UV/ELSD/MS), wavelength, gradient, and solvent system used, as these can impact apparent purity. Baseline-separated minor isomers or salts may require orthogonal methods for full accounting.
• Residual solvents and water: If relevant to your application, request GC residual solvent data and Karl Fischer water content; these are not provided in this listing.
• Polymorph/salt form: If the compound exists as different forms (free base, salt, solvate), ensure the supplied form matches your experimental plan; confirm by XRPD or 13C SSNMR if necessary.
• Stabilizers/inhibitors: None are listed for this item. If stabilizers are present in a particular lot, they will appear on the CoA; assess potential impact on bioassays.

Documentation and traceability:

• This item is for research use only. Request and archive the product CoA, lot/traceability information, and SDS for GLP/GMP-adjacent environments (without implying GMP status).

Reaction and Applications

This product is offered as a research-use small molecule (screening/chemical biology). It is not typically used as a synthetic reagent or catalyst.

• Synthetic reaction applications: Not generally applicable. No manufacturer reaction use is specified.
• Practical usage focus: Preparation of analytical standards, control compounds, and screening stocks for biochemical or cell-based assays.
• If chemical modification is intended (derivatization or probe synthesis), first confirm the exact structure, functional handles, and salt form from the CoA/SDS or primary literature associated with CAS 2080410-41-7, then develop a bespoke route.

For reagent-like use cases (general guidance only):

• Without known functional groups, do not assume compatibility with air/moisture, acids/bases, or oxidants. Pilot small-scale tests and monitor by LC-MS.
• If coupling to tags (biotin/fluorophores), consider installing linkers via amide or click chemistry only after verifying that such handles exist in the scaffold or can be introduced via a planned synthetic route.

Reaction Conditions

Not applicable as a reagent: No manufacturer-supported use in chemical reactions is provided for this product. Accordingly, there are no endorsed reaction conditions, catalysts, or solvent systems for synthetic transformations involving GSK3494245.

If your research intends to transform or derivatize this compound (general guidance only):

• Establish structure and functional groups from authoritative sources (CoA/SDS/literature) before attempting chemistry.
• Begin with micro-scale scouting reactions under inert atmosphere where air/moisture sensitivity is suspected; monitor by LC-MS.
• Use anhydrous, oxygen-free solvents when handling sensitive motifs (e.g., boronates, aldehydes), but note that such motifs are not established for this item.
• Purify using methods compatible with the compound’s stability (e.g., reverse-phase prep HPLC versus silica) only after confirming chromatographic behavior with analytical scouting.

Because no target reactivity is provided, treat any conditions below as non-applicable to this catalog item. Expected yields, named reactions, and temperature windows are intentionally omitted to avoid implying unsupported specifications.

Safety and Handling

Safety classification details are not specified in this listing. Always consult the lot-specific SDS for authoritative information.

• GHS classification, signal word, pictograms, H-statements: Not specified for this item; refer to SDS.
• Likely hazards (general for research small molecules): May be harmful if swallowed, inhaled, or in contact with skin; may cause irritation. Avoid aerosol formation and contact with eyes/skin.

Handling recommendations (general best practice):

• PPE: Wear lab coat, safety glasses, and suitable gloves (e.g., nitrile). Handle powders in a fume hood to avoid inhalation.
• Aseptic/clean technique: Use dry, chemically clean tools to prevent cross-contamination of screening libraries.
• Incompatibilities: Unknown for this specific item; as a precaution, segregate from strong oxidizers, acids/bases until compatibility is known.
• Hygroscopicity/light sensitivity: Unknown; protect from moisture and light as a precaution when preparing stock solutions and during weighing.

First-aid (overview; defer to SDS):

• Inhalation: Move to fresh air; seek medical advice if symptoms persist.
• Skin/eye contact: Rinse with plenty of water for ≥15 minutes; remove contaminated clothing; seek medical advice if irritation continues.
• Ingestion: Rinse mouth; do not induce vomiting; obtain medical attention.

Spill/leak procedures (general):

• For solids: Avoid dust; sweep with minimal disturbance; collect in sealed container for disposal.
• For solutions: Absorb with inert material, ventilate area, and decontaminate surfaces.

Disposal: Follow institutional chemical waste protocols; do not release to drains.

Solvent Selection

No item-specific solubility or polarity data are provided for GSK3494245. The following guidance outlines a pragmatic approach for preparing screening stocks of unknown or variably soluble discovery compounds (general best practice, not item-specific):

• Primary solvent choice:
  • DMSO (anhydrous, ≥99.9%) is the default for 10–50 mM master stocks due to broad solvating power and assay compatibility at ≤0.5% v/v in most systems.
• Secondary solvents for pre-dissolution (if DMSO alone is insufficient):
  • DMF, NMP, or ethanol (anhydrous). Combine with DMSO in small fractions (e.g., 10–30%) to assist dissolution, then back-dilute into aqueous buffers.
• Aqueous workup/dilution:
  • Dilute DMSO stocks into assay buffer containing surfactant (e.g., 0.01–0.05% Tween 80) or protein (e.g., 0.1% BSA) to mitigate precipitation and adsorption, where assay-compatible.
• Solubility screening workflow:
  • Prepare a 1–2 mg/mL suspension in several solvents (DMSO, DMF, MeOH, EtOH) and evaluate clarity after vortex/sonication. Confirm by HPLC if needed.
• Adsorption and carryover:
  • Use low-bind tubes/plates; pre-wet tips with DMSO to reduce losses of hydrophobic compounds.
• Light/air sensitivity:
  • Absent item-specific data, minimize exposure to light and air; consider amber vials and inert gas headspace when feasible.

Comparison (general): DMSO offers the broadest applicability; ethanol is greener but often limited by solubility for highly lipophilic scaffolds; DMF/NMP enhance solubility but are less desirable for HTS due to cytotoxicity and assay interference.

Storage and Reconstitution

Storage conditions and shipping are provided for this item; follow strictly to preserve integrity.

• Storage (from product data): Store at -80°C.
• Shipping (from product data): Shipped on dry ice packs + cold packs.
• Container handling: Keep tightly closed in the original container. Minimize freeze–thaw and moisture ingress.

Reconstitution and aliquoting (general best practice; not item-specific):

• Before opening, allow the sealed container to equilibrate to room temperature in a desiccator to prevent condensation.
• If solid: Prepare a concentrated stock (e.g., 10–50 mM) in anhydrous DMSO unless item-specific guidance indicates otherwise. Vortex/sonicate as needed; verify dissolution visually and by analytical HPLC if critical.
• If solution: Mix gently after thaw; avoid vigorous vortexing if foaming is problematic. Confirm concentration where accuracy is required (qNMR or LC with a calibrated standard).
• Aliquoting: Dispense single-use aliquots (e.g., 10–50 µL) in inert, low-bind, amber vials or tubes; backfill headspace with inert gas when feasible.
• Freeze–thaw: Avoid repeated cycles. Store aliquots at -80°C; for short-term working stocks, -20°C may be acceptable if stability is verified experimentally.
• Light and moisture: Protect from light (foil-wrapped amber vials) and humidity; use a desiccant in secondary containment.

Stability/shelf life: Not specified for this item; refer to CoA/Spec Sheet and perform in-house stability checks (e.g., LC-MS at defined intervals).

Structure and Identity

Brief overview: GSK3494245 is supplied as a research-use small molecule screening compound. Item-specific structural identifiers are limited in the current listing.

• SKU: G656818
• Product name: GSK3494245
• CAS: 2080410-41-7 (catalog identifier)
• PubChem CID: 126571915 (catalog cross-reference)
• 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.

Structural features (general notes):

• Functional groups, ring systems, and stereochemistry are not provided in the current product data. Consult the CoA/SDS or primary literature associated with the CAS or CID for definitive structural information.
• 2D/3D depiction: Not included in this listing. If required for computational or analytical work, retrieve the connection table from a trusted database (e.g., PubChem for the given CID) and verify against the lot-specific CoA.

Identity verification guidance (general):

• Recommended orthogonal checks for small-molecule library items include HRMS (exact mass), 1H/13C NMR, and an HPLC/UPLC purity trace. Where chirality is relevant, apply chiral HPLC or polarimetry as appropriate.
• Match any retrieved public structure to the lot-specific documentation; small-molecule code names can correspond to multiple salts, polymorphs, or stereochemical variants in the literature.

Synthetic Utility

GSK3494245 is offered as a finished small-molecule screening compound and is not positioned as a synthetic building block or reagent in this catalog entry.

• Building block value: Not specified. Without disclosed functional groups, we cannot recommend specific transformations (e.g., cross-coupling, amide formation).
• Derivatization (general guidance): If the scaffold and functional handles are known from independent structural data, common late-stage modifications might include acylation/alkylation of amines/alcohols, heteroatom substitutions, or installation of linkers for conjugation. Such modifications require confirmed structure and compatibility assessment.
• Retrosynthetic planning: Any synthetic route development should be based on a validated structure (confirm via CoA/SDS and peer-reviewed sources for CAS 2080410-41-7) and may involve protection/deprotection strategies standard to heteroaromatic/biaryl scaffolds common in discovery chemistry.

Conclusion: Treat this item as an end-use screening compound. Do not assume reagent-like behavior or reactivity in the absence of explicit structural information.

Target Specificity

Target information is not provided for this product.

• Primary target/pathway: Not specified for this item; refer to CoA/Spec Sheet and primary literature associated with CAS 2080410-41-7 or CID 126571915.
• Species reactivity, selectivity profile, binding constants: Not specified for this item; refer to CoA/Spec Sheet.

Guidance for users (general):

• If employing this compound as a tool molecule, corroborate target claims using orthogonal assays (biochemical and cellular) and counterscreens to rule out assay interference.
• Document lot numbers alongside any target-activity data you generate to ensure reproducibility and traceability.