THR-β agonist 3 , CAS No.2656400-84-7

CAS: 2656400-84-7 Cat. No.: T1451415 Summenformel: C₂₉H₃₂ClO₅P Molekulargewicht: 526.99

Storage

Store at -20°C

Shipped In

Ice chest + Ice pads

Übersicht

THR-β agonist 3 is a potent agonist of THR-β. THR-β agonist 3 has the potential for the research of metabolic diseases such as obesity, hyperlipidemia, hypercholesterolemia, diabetes and other conditions such as steatosis and non-alcoholic steatohepatitis (NASH), atherosclerosis and other related conditions and diseases (extracted from patent WO2021129827A1, compound 6).

Specifications

Storage

Store at -20°C

Verschickt in

Ice chest + Ice pads

Dieses Produkt erfordert Kühlkettenversand. Grundversand und andere Economy-Optionen sind nicht verfügbar.

Namen und Kennungen

Molekulargewicht

526.99

Application Protocols

No item-specific, validated application protocols are provided in the Product Data for SKU T1451415.

General protocol outlines for THR-β agonists (literature; not item-specific):

• Reporter assay (TRE-luciferase):
  • Plate THR-β–expressing cells or co-transfect cells with THR-β and TRE-luc constructs.
  • Dose with serial dilutions of compound (maintain constant DMSO across wells; include T3 and vehicle controls).
  • Incubate 16–24 h; measure luciferase activity; fit concentration–response curves to obtain EC50/Emax.
• Endogenous gene expression (qPCR):
  • Treat THR-β–competent cells with compound for 6–24 h.
  • Isolate RNA; perform RT–qPCR for THR-responsive genes; normalize to housekeeping genes.
• Coactivator recruitment (TR–coactivator TR-FRET):
  • Use recombinant THR-β LBD and labeled coactivator peptide.
  • Titrate compound; measure TR-FRET signal to derive binding/efficacy parameters.

Important: These are general templates only. Optimize cell type, dosing regimen, and readouts for your system. For item-specific usage recommendations, consult the CoA/Spec Sheet.

Biological Roles

General/literature context (not item-specific):

• Thyroid hormone receptors (THRs) are nuclear hormone receptors with isoforms THR-α and THR-β that bind endogenous ligands such as triiodothyronine (T3). THR-β is enriched in liver and certain CNS regions and plays key roles in metabolic rate, lipid handling, and feedback regulation of the hypothalamic–pituitary–thyroid axis.
• THR agonists promote recruitment of coactivators and displace corepressors, driving transcription of genes involved in mitochondrial biogenesis, fatty acid oxidation, and cholesterol metabolism. Selective THR-β agonists are used in research to dissect liver-dominant metabolic pathways while minimizing THR-α–mediated cardiovascular or skeletal effects.
• In cell models, THR activation can be monitored via reporter gene systems (TRE-driven luciferase), endogenous gene readouts (e.g., CPT1A, DIO1, ANGPTL4; literature examples), or proteomic/metabolomic signatures indicative of increased oxidative metabolism.
• Downstream signaling is context-dependent and influenced by receptor abundance, coregulator expression, and cellular thyroid status. Time-dependent responses typically span from rapid chromatin/cofactor changes (minutes–hours) to transcriptional and metabolic remodeling (hours–days).

Caveats:

• Potency, efficacy, and selectivity are compound-specific; do not infer these for this catalog item without consulting primary data. Use appropriate controls (vehicle, T3, and isoform-selective comparators) when interpreting biological outcomes.

Buffer Applications

This product is a bioactive small molecule and is not itself a buffering agent. It does not define a specific pH range or buffering capacity.

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

• Use physiologically relevant buffers (e.g., HEPES- or phosphate-buffered saline) compatible with your biological system. Maintain consistent ionic strength and pH (commonly pH 7.2–7.4 for mammalian cells).
• When dosing from DMSO stocks, ensure the final DMSO percentage is consistent across all wells/samples, including controls. Consider adding carrier proteins (e.g., 0.1% fatty acid–free BSA) if nonspecific binding or adsorption is suspected.

For precise buffer recipes and pH ranges, refer to your assay protocol; the compound does not substitute for standard buffering systems.

Green Alternatives

As a bioactive small-molecule ligand, the primary environmental considerations relate to solvent choice and waste minimization during assay preparation, rather than substitution of the active itself.

Greener practice guidance (general; not item-specific):

• Prefer aqueous-buffered systems with minimal DMSO (≤0.1–0.2% v/v where feasible) while maintaining compound solubility and assay performance.
• If organic co-solvent is necessary, evaluate ethanol as a potentially greener alternative to DMF or NMP, subject to cell compatibility and data integrity.
• Scale down: Use microplate formats and miniaturized assays to reduce total solvent and consumable usage.
• Waste segregation: Collect DMSO/organic solutions as hazardous waste; avoid drain disposal. Rinse vials with minimal solvent.

Illustrative comparison (general; not item-specific):

• DMSO vs DMF: DMSO generally offers lower toxicity and better biodegradability than DMF; choose DMSO when compatible with your assay.
• Ethanol vs acetonitrile: Ethanol is renewable and less hazardous; however, acetonitrile may be required for certain analytical workflows—use only as needed and recover via solvent recycling when possible.

Documentation:

• Record final solvent percentage in all experiments to ensure reproducibility and to support method transfer with minimized environmental footprint.

Pharmaceutical Uses

No pharmaceutical or clinical use is claimed or supported for this catalog item. For research use only.

General formulation context for research (not item-specific):

• In preclinical research workflows, small-molecule nuclear receptor ligands are commonly formulated as DMSO stocks for in vitro studies, and as vehicle-based suspensions/solutions for exploratory in vivo models (e.g., aqueous buffers with cosolvent/surfactant systems). Any in vivo use must follow institutional approvals and safety reviews.
• Excipient considerations include solvent tolerance (DMSO, ethanol), surfactants (polysorbates), and pH/osmolality of the dosing vehicle. Filter sterilization may be required for cell culture.

Regulatory note:

• This product is not intended for human or veterinary use, diagnostic procedures, or as an API. No compendial (USP/EP/JP) monograph is implied.

For any downstream translational work, users are responsible for verifying identity, purity, and stability independently and complying with all applicable regulations.

Physical Properties

Item-specific physical constants are not provided in the current listing. Where values are essential for your workflow, please consult the CoA/Spec Sheet for the specific lot.

Item-specific (from 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.
• Melting point (MP): Not specified for this item; refer to CoA/Spec Sheet.
• Boiling point (BP): Not specified for this item; refer to CoA/Spec Sheet.
• Density: Not specified for this item; refer to CoA/Spec Sheet.
• Refractive index: Not specified for this item; refer to CoA/Spec Sheet.
• Solubility: Not specified for this item; refer to CoA/Spec Sheet.

General/literature guidance for small-molecule THR-β agonists (not item-specific):

• Aggregated experience suggests many THR-β agonists are sparingly soluble in water and are commonly prepared as concentrated DMSO stock solutions (e.g., 10–50 mM, literature) for biological assays, then diluted into aqueous buffers to achieve low final DMSO fractions (≤0.1–0.5% v/v, literature best practice).
• Octanol/water partitioning (logP/logD) tends to be in the moderate lipophilicity range, supporting cell permeability; exact values are chemotype-dependent (consult the CoA or primary literature for this specific CAS).
• Solid state: Many analogs are crystalline or amorphous solids at ambient temperature; hygroscopicity varies by substitution pattern.

Notes:

• Reported numerical values from literature should not be used as specifications. For QC-critical parameters, rely solely on the CoA/Spec Sheet supplied with your lot.

Quality and Grades

Item-specific quality grade and purity are not listed in the provided Product Data. Please refer to the CoA/Spec Sheet for the exact assay/purity, residual solvent profile, and any stabilizers.

What grade means in practice (general guidance):

• Research grade: suitable for most discovery and mechanistic studies; analytical characterization typically includes NMR and LC/GC analytical purity.
• HPLC grade (if applicable): emphasizes low UV-absorbing impurities and high purity by chromatographic criteria—useful for analytical standards and cell-based assays sensitive to impurities.
• Bioactive small-molecule grade: often controlled for identity (NMR/MS), purity (HPLC/UPLC), and sometimes endotoxin/bioburden where relevant to cell assays (verify on CoA).

Stabilizers/antioxidants:

• Not specified for this item; refer to CoA/Spec Sheet. If present, stabilizers can influence assay design (e.g., background absorbance/fluorescence) and may appear in LC/MS traces.

Batch-specific documentation:

• CoA typically includes: assay/purity, identity confirmation (1H NMR, MS), water/volatile content (e.g., KF/LOD), and storage guidance. Where UV cutoff or metal limits are critical, consult the Spec Sheet.

Recommendation:

• For quantitative biology or SAR work, document the exact lot, purity, and any counterions/solvates. Re-verify purity after extended storage or multiple freeze–thaw cycles.

Reaction and Applications

This product is a bioactive small-molecule ligand rather than a synthetic reagent; classical organic reaction applications (e.g., cross-coupling, oxidations) are not its primary use.

Research applications (general/literature; not item-specific):

• Nuclear receptor pharmacology: activation of thyroid hormone receptor beta (THR-β) in cell-based reporter assays to quantify agonist potency and efficacy relative to T3.
• Gene regulation studies: modulation of THR-β target genes (e.g., metabolic, mitochondrial, and lipid-handling programs) in cultured cells or primary tissues, measured by qPCR, RNA-seq, or proteomics.
• Selectivity profiling: comparison of responses in THR-β vs THR-α expressing systems to assess isoform selectivity, including coactivator recruitment assays.
• Structural biology: potential use in LBD binding or crystallography screens to stabilize specific receptor conformations (binding confirmation via ITC/SPR/DSF, literature).
• Chemical biology: time-course perturbation studies to map downstream pathways; combination experiments with pathway inhibitors.

Practical considerations:

• Prepare and store concentrated DMSO stocks; confirm solubility and absence of aggregation under assay conditions (inspect and/or use light scattering).
• Include vehicle controls and, where relevant, positive controls (e.g., triiodothyronine, T3) for assay benchmarking.
• Titrate across several logs (e.g., 10-point serial dilutions) to obtain full concentration–response curves and derive EC50/ECmax (assay/literature practice).

Note: For synthetic chemistry workflows, this compound is not typically used as a building block; see Synthetic Utility for limitations.

Reaction Conditions

Classical synthetic reaction conditions are not applicable to the end use of this product. Instead, consider assay preparation and dosing conditions for biological evaluation.

Assay preparation conditions (general/literature; not item-specific):

• Stock solutions: prepare at high concentration in anhydrous DMSO (e.g., 10–50 mM, literature) to minimize vehicle in assays. Verify complete dissolution by visual inspection and, if needed, brief sonication.
• Working solutions: dilute into prewarmed assay media or buffer to target final DMSO ≤0.1–0.5% v/v. Mix thoroughly to prevent local supersaturation and precipitation.
• Concentration ranges: for potency determination, perform multi-log serial dilutions (e.g., 10-point, 3-fold steps) spanning at least 0.1 nM to 30 μM, adjusted per expected potency and assay sensitivity (literature practice).
• Incubation: THR-mediated transcriptional responses often require 6–24 h to manifest in reporter assays; gene-expression endpoints may require 12–48 h (literature examples). Optimize per system.
• Controls: include vehicle, a reference agonist (e.g., T3), and, where relevant, THR isoform-selective comparators. Confirm absence of cytotoxicity at top concentrations (e.g., viability assay in parallel).

Stability considerations:

• Protect from repeated freeze–thaw; aliquot stocks. Check for precipitation or color change. For long incubations or light exposure, consider amberware and reduced light conditions.

These conditions are provided as general guidance and are not specifications for this catalog item.

Safety and Handling

Safety classification for this catalog item is not specified. Always handle according to prudent laboratory practice and consult the Safety Data Sheet (SDS) for authoritative information.

Item-specific hazard data (from Product Data):

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

General laboratory precautions (good practice; not item-specific):

• Personal protective equipment: lab coat, safety glasses, and appropriate chemical-resistant gloves (e.g., nitrile). Avoid inhalation, ingestion, and skin or eye contact.
• Engineering controls: work in a fume hood when weighing powders or preparing solutions; minimize aerosol and dust generation.
• Storage incompatibilities: segregate from strong oxidizers and strong acids/bases unless compatibility is confirmed. Keep desiccated and protected from light if the compound is photo- or moisture-sensitive (consult CoA/SDS).
• First aid (overview; defer to SDS): rinse eyes/skin with water for at least 15 minutes upon contact; remove contaminated clothing; seek medical evaluation. If inhaled, move to fresh air. If swallowed, rinse mouth; do not induce vomiting unless directed by medical personnel.

Waste disposal:

• Dispose of unused material and solutions as organic chemical waste according to institutional and local regulations. Avoid drain disposal.

Note: Some small-molecule ligands can exhibit biological activity at low concentrations—handle with care to avoid exposure.

Solvent Selection

Item-specific solubility data are not provided; select solvents based on general behavior of small-molecule THR-β agonists and pilot tests.

General solvent guidance (literature/best practice; not item-specific):

• Primary stock solvent: DMSO is commonly used due to broad solvating power and compatibility with biological assays at ≤0.1–0.5% v/v final concentration. DMF or ethanol can be alternatives, subject to cell-line tolerance.
• Aqueous buffers: Most THR-β agonists are poorly water-soluble; prepare concentrated organic stocks, then dilute into assay buffer with vigorous mixing. Use co-solvent strategies (DMSO + minimal surfactant such as 0.01–0.1% Tween-80) only if validated for the assay.
• Solvent polarity/miscibility: DMSO (highly polar, fully miscible with water) facilitates precise dosing; ethanol offers rapid evaporation for coating applications but may affect membrane integrity in cells at >0.5–1% v/v.

Comparison (general):

• DMSO: maximal solubilization; low volatility; low UV background above ~260 nm.
• Ethanol: volatile, convenient for rapid evaporation; limited aqueous tolerance in cells.
• DMF: strong solvent but more cytotoxic; minimize final concentration (≤0.1% v/v suggested, assay-dependent).

Practical tips:

• Filter sterilize final working solutions where sterility is required (0.22 μm PTFE or PES compatible with selected solvent).
• Confirm absence of precipitate at working concentrations over assay duration. Perform vehicle controls matched to final solvent percentage.

Storage and Reconstitution

Item-specific storage and shipping (from Product Data):

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

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

• Solvent: Dissolve the compound in anhydrous DMSO to prepare a concentrated stock (e.g., 10–50 mM, as solubility permits). If an alternative solvent is required (ethanol, DMF), verify compatibility with your assay and materials.
• Technique: Allow vial to equilibrate to room temperature in a desiccator before opening to prevent moisture condensation. Briefly centrifuge to collect contents, then add solvent. Mix by gentle vortexing; if needed, sonicate briefly to aid dissolution. Avoid excessive heating.
• Sterility: For cell-based assays, pass working solutions through a 0.22 μm sterile filter compatible with the solvent system.
• Aliquoting: Dispense single-use aliquots to minimize freeze–thaw cycles. Store aliquots tightly sealed at −20°C (or per updated CoA guidance). Protect from light if the compound is photosensitive (check Spec Sheet).

Stability monitoring:

• Inspect for precipitation, discoloration, or changes in chromatographic purity over time. Reassess purity by HPLC/UPLC for long-term studies or critical experiments.

Note: Where specific solubility limits, pH stability, or hygroscopicity are critical, these must be confirmed from the CoA/Spec Sheet for the lot you receive.

Structure and Identity

Overview: THR-β agonist 3 is described as a small-molecule ligand intended to activate the thyroid hormone receptor beta (THR-β). Item-specific structure identifiers are not provided in the current listing.

Item-specific identifiers (from Product Data):

• CAS: 2656400-84-7
• InChIKey: Not specified for this item; refer to CoA/Spec Sheet.
• SMILES: Not specified for this item; refer to CoA/Spec Sheet.
• Molecular Formula: Not specified for this item; refer to CoA/Spec Sheet.
• Molecular Weight: Not specified for this item; refer to CoA/Spec Sheet.

Structural features (general/literature context for THR ligands; not item-specific):

• Many selective THR-β agonists are nonpolar to moderately lipophilic, with heteroatoms (e.g., O, N, halogens) positioned to mimic key thyroid hormone interactions (hydrogen-bond donors/acceptors and halogen-binding pockets) within the ligand-binding domain of THR-β.
• Typical scaffolds include substituted phenyl/aryl–ether frameworks, bicyclic or polycyclic aryl systems, and polar handles to tune selectivity and PK. Stereochemistry is not universally required across the class but may be present in specific chemotypes.

2D structural description (general/literature; not item-specific):

• A compact aromatic core bearing one or more heteroatom-containing substituents to engage H12 positioning in THR-β LBD.
• Lipophilic surface area balanced with limited polarity to enable cell permeability; ionizable groups are less common than in peptide ligands.

Identity verification guidance:

• For definitive structural identity (SMILES, InChI, MF/MW), consult the product CoA/Spec Sheet or reach out to Aladdin Scientific with the SKU T1451415 for the current batch record.

Synthetic Utility

This compound is supplied as a bioactive small-molecule ligand and is not intended as a general synthetic reagent or building block.

General observations for similar chemotypes (literature; not item-specific):

• THR-β agonists often contain densely substituted aryl/heteroaryl motifs and may include metabolically optimizing substituents (e.g., halogens, ether linkages). Such molecules are typically end-of-line targets rather than synthetic handles.
• Functional group interconversion on these scaffolds can be challenging due to dense substitution and the risk of altering receptor-binding pharmacophores.

When synthetic derivatization is desired (SAR exploration):

• Parallel synthesis typically proceeds from earlier intermediates (boronates/halides for cross-coupling, nucleophilic aromatic substitutions, or late-stage amide/urea formations). Direct modification of the final agonist is usually limited to protecting-group removal, salt formation, or isotopic labeling.

Conclusion:

• Treat this item as a finalized bioactive compound. If building-block functionality is required, consult the medicinal chemistry route to access upstream intermediates better suited to diversification.

Target Specificity

Item-specific target validation data (e.g., selectivity ratios, binding affinities, or assay-proven specificity to THR-β over THR-α) are not provided in the Product Data.

Given the product name, the intended research target is thyroid hormone receptor beta (THR-β); however, quantitative selectivity and off-target profiles for this exact item must be confirmed experimentally or obtained from the CoA/Spec Sheet or primary literature for CAS 2656400-84-7.

No antibody/biologic attributes (antigen, epitope, clone, isotype, species reactivity) apply to this small-molecule ligand.