THR-β agonist 1 , CAS No.2648403-17-0

CAS: 2648403-17-0 Cat. No.: T1454532 Formula: C₁₇H₁₄Cl₂FN₅O₄ Peso molecolare: 442.23

Storage

Store at -20°C

Shipped In

Ice chest + Ice pads

Panoramica

THR-β Agonist 1 is a potent and selective agonist of THRβ. Thyroid hormone receptor mediates the physiological activity of thyroid hormones which plays a key role in normal growth and development of the body and in maintaining metabolic balance. THR-β Agonist 1 has the potential for the research of thyroid hormone receptor-related diseases (extracted from patent WO2021104288A1, compound 2).

Specifications

Condizioni di conservazione di stoccaggio

Store at -20°C

Spedito in

Ice chest + Ice pads

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

Nomi e identificatori

• Peso molecolare: 442.23

Application Protocols

The following protocols are general, literature-based guidelines for small-molecule THR-β agonists and are not item-specific. Adjust to your cell line, receptor construct, and instrumentation.

1. THR Reporter Gene Assay (cell-based)

• Plate THR-β–expressing cells harboring a TRE-luciferase reporter at 1–2 × 10^4 cells/well (96-well) in complete medium.
• Prepare ligand serial dilutions (10-point, 1:3 or 1:2) in DMSO, then pre-dilute 1:100 in medium to keep final DMSO ≤0.1–0.5%.
• Treat cells for 16–24 h. Include vehicle and a reference agonist (e.g., T3) controls.
• Read luciferase signal; fit 4-parameter logistic curves to obtain EC50 and Emax.

2. TR-FRET Coactivator Recruitment (biochemical)

• Use purified human THR-β LBD (donor-labeled) and a fluorescein-labeled coactivator peptide (e.g., SRC-1 fragment) per kit/vendor instructions.
• Titrate ligand (0.01 nM–1 μM) in HEPES 50 mM, NaCl 100 mM, 0.01% Tween-20, 0.1% BSA, pH 7.4; 1% DMSO final.
• Incubate 1 h at RT; read TR-FRET ratio; derive EC50.

3. Gene Expression Confirmation (qPCR)

• Treat THR-β–competent cells with ligand near EC80 for 6–24 h.
• Extract RNA, synthesize cDNA, and quantify transcripts of canonical THR-responsive genes (e.g., DIO1, ME1) normalized to housekeeping controls.

General tips

• Verify compound solubility at top concentrations; avoid precipitation.
• Use low-bind plastics; protect from light; prepare fresh working solutions.
• Report concentrations as free base equivalents; confirm from CoA/Spec Sheet.

Biological Roles

Context (literature/general):

• THR-β (NR1A2) is a nuclear hormone receptor that binds triiodothyronine (T3) and regulates transcription by recruiting coactivators/corepressors at thyroid hormone response elements. THR-β is prominent in liver, kidney, and certain regions of the CNS, with roles in metabolic rate, lipid/cholesterol homeostasis, and auditory function in developmental contexts.
• A selective THR-β agonist is used to experimentally activate THR-β with reduced engagement of THR-α, enabling dissection of β-driven transcriptional programs.

Typical research applications (no clinical/medical claims):

• Mechanistic studies of nuclear receptor signaling, coactivator recruitment (e.g., SRC-1, TRAP/DRIP), and chromatin remodeling at target promoters.
• Transcriptomic profiling of THR-β–responsive genes (e.g., DIO1, CYP7A1, ME1; literature exemplars) in hepatic cell lines and primary hepatocytes.
• Metabolic pathway interrogation in vitro: fatty acid oxidation, lipogenesis, and reverse cholesterol transport gene networks.
• Selectivity assessment in recombinant cell systems co-expressing THR-α vs THR-β to quantify subtype bias.

Assay modalities (examples):

• Cell-based reporter assays (DR4/IR0 TRE-driven luciferase) to measure agonism and potency.
• TR-FRET or fluorescence polarization binding assays using purified ligand-binding domains.
• Thermal shift (DSF) and isothermal titration calorimetry (ITC) for direct engagement and thermodynamics.

Note: Exact potency, efficacy, and selectivity values for this item are not specified; consult CoA/Spec Sheet or evaluate in-house under your assay conditions.

Buffer Applications

Item-specific buffer guidance: Not specified for this item; refer to CoA/Spec Sheet. The following are general, practical considerations for preparing and using solutions of small-molecule THR-β agonists in biological assays.

Stock preparation (general):

• Dissolve in anhydrous DMSO to 10–50 mM. Warm gently (≤37°C) and vortex/sonicate briefly if needed. Protect from light. Record exact concentration by weight-in or qNMR if critical.

Dilution into aqueous systems (general):

• For cell culture: Add DMSO stock to pre-warmed complete medium with thorough mixing; typical final DMSO ≤0.1–0.5% v/v (literature guidance). Include vehicle controls at the same DMSO %.
• For biochemical buffers: HEPES or Tris (pH 7.4–8.0) with 50–150 mM NaCl is commonly used. Include 0.01–0.05% Tween-20 or 0.1 mg/mL BSA if nonspecific adsorption is observed.
• Avoid local supersaturation: Pre-dilute the DMSO stock 1:10 in buffer/medium before the final addition to assay plates when feasible.

Stability and adsorption (general):

• Minimize time in dilute aqueous solution; prepare fresh working solutions daily unless stability is verified.
• Use low-bind tubes and tips; pre-rinse plasticware with working buffer containing carrier protein if adsorption is an issue.

Sterility:

• Filter sterilize final working solutions through 0.22 μm PVDF/PTFE if sterility is required and chemistry is compatible.

Compatibility checks:

• Visually inspect for haze/precipitate; measure absorbance at 600–700 nm to detect light scattering if in doubt. Adjust solvent % or add carrier protein accordingly.

Green Alternatives

Green chemistry considerations are generally oriented toward solvents and bulk reagents. For a specialized bioactive ligand such as THR-β agonist 1, there is no direct “green alternative” with identical function. Selection is driven by biological performance (potency, selectivity) rather than process mass intensity.

Nevertheless, greener practice can be applied in handling and assay setup (general guidance):

• Solvent choice: Favor minimal DMSO volumes and consider ethanol where compatible to reduce reliance on high-boiling polar aprotics. Validate biological equivalence.
• Concentrate stocks to reduce total solvent usage and shipping mass.
• Waste minimization: Plan serial dilutions to avoid excess solution preparation; consolidate rinses; use microscale assay formats (96–384 well) to lower solvent consumption.
• Energy: Store consolidated aliquots to minimize freezer door-open time; batch experimental runs to reduce repeated thaw cycles.

Comparison of common stock solvents (general):

• DMSO: High solvency; low volatility; difficult to recover/recycle at small scale.
• Ethanol: Renewable feedstocks available; higher volatility facilitates recovery; may be less effective for very lipophilic ligands.

For process development where larger quantities of functionally similar ligands are prepared, consider greener synthetic routes, biocatalytic transformations, and solvent swaps based on solvent selection guides. Such route-level choices are outside the scope of this catalog item.

Pharmaceutical Uses

This product is supplied strictly for research use only. No medical, diagnostic, or therapeutic applications are intended or permitted.

Relevant roles in pharmaceutical R&D (literature/general):

• Reference agonist/control: Used as a positive control in high-throughput screening (HTS), hit triage, and assay validation for THR-β–targeted programs.
• Mechanistic probe: Enables evaluation of pathway engagement, target modulation biomarkers, and structure–activity relationships (SAR) in medicinal chemistry campaigns.
• ADME method development: Useful for establishing chromatographic methods, stability protocols, and microsomal turnover assays for THR-β ligand chemotypes (when permitted by internal policies).
• Formulation screening (preclinical research only): Solubility and vehicle compatibility studies for in vitro delivery; typical vehicles include DMSO, ethanol, and aqueous buffers with acceptable co-solvent percentages.

Compliance and documentation:

• Identity, purity, and form (free base/salt) should be confirmed from the CoA/Spec Sheet for dose calculations.
• Any use in regulated workflows (e.g., GLP method development) requires verification that the supplied documentation and quality attributes meet your internal standards.

Note: Pharmacopeia monographs, excipient status, and clinical/formulation specifications are not applicable to this research reagent unless explicitly stated on accompanying documentation. For this item, such status is not specified.

Physical Properties

Item-specific properties (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.

Safety/handling summary is provided in a separate tab.

Typical physical behavior of small-molecule nuclear receptor agonists (literature/general — not item-specific):

• State: Often solid powders at ambient conditions.
• Solubility: Frequently sparingly soluble in water; readily soluble in aprotic polar organics (DMSO, DMF) and moderately in ethanol/MeOH depending on functionality.
• LogP: Commonly moderate to high (cLogP ~2–6) consistent with lipophilicity needed for intracellular access.
• pKa: Many scaffolds are neutral or weakly basic/acidic; ionization state is scaffold-dependent.
• Stability: Many ligands are stable as dry solids under inert, desiccated conditions; some may be light- or moisture-sensitive depending on functional groups.
• UV/Vis: Aromatic systems typically show UV absorbance in 230–320 nm range; exact λmax is scaffold-dependent.

Measured values for this specific item (BP, MP, density, solubility, logP, pKa, refractive index, UV cutoff):

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

Practical notes (general):

• Prepare concentrated stocks in anhydrous DMSO (e.g., 10–50 mM) for accurate dosing into aqueous assays. Vortex and brief sonication may aid dissolution. Filter sterilize (0.22 μm PTFE) if sterility is required. Verify clarity at working dilutions to avoid precipitation or colloid formation.

Quality and Grades

Item-specific quality information:

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

General guidance on quality for small-molecule bioactives (literature/general):

• Chemical purity: For cellular and biochemical assays, ≥95% purity by HPLC/UPLC is commonly targeted to minimize off-target effects from impurities. The exact acceptance criteria should be verified on the item’s CoA.
• Identity confirmation: Typical orthogonal methods include 1H NMR, LC–MS, HRMS, and HPLC purity with a reported detection wavelength. Where available, residual solvents and water (KF) may also be reported.
• Counter-ions/salt form: Many ligands are supplied as free bases/acids or specific salts to enhance handling. Verify the form on the CoA; this affects MW for dosing.
• Stabilizers: If stabilizers/antioxidants are present, they will be listed on the CoA/Spec Sheet. For this item, stabilizer usage is not specified.
• Endotoxin/bioburden: Generally not specified for small molecules, but sterile filtration of solutions can reduce bioburden for sensitive biological systems.

Practical QA notes:

• Upon receipt, inspect packaging integrity and label. If available, compare lot CoA against your internal assay acceptance thresholds (e.g., purity, single peak profile, residual solvent limits).
• For quantitative biology, perform an in-house qNMR or LC–MS purity check, especially if your assay is sensitive to trace impurities.
• Record the exact lot MW (if salt/solvate) for accurate molar dosing.

Reaction and Applications

This product is a bioactive small-molecule agonist intended for biological research, not a synthetic reagent. As such, traditional synthetic “reaction applications” (e.g., use as a coupling partner, catalyst, or stoichiometric reagent) are not typically applicable.

For researchers, the most relevant uses relate to probing thyroid hormone receptor beta signaling:

• Cell-based reporter assays to quantify THR activation.
• Biochemical binding or coactivator recruitment assays (e.g., TR-FRET, AlphaScreen) to determine affinity and efficacy.
• Gene expression modulation experiments to profile THR-β–regulated transcripts.

If you require a synthetic intermediate or building block version of this scaffold, consult Aladdin Scientific for related catalog items. Otherwise, please refer to “Biological Roles,” “Target Specificity,” and “Application Protocols” for practical guidance on experimental use.

Reaction Conditions

Not applicable to this product’s intended use. THR-β agonist 1 is a research ligand for biological assays, not a reagent employed under synthetic reaction conditions.

Assay conditions (literature/general, non-item-specific) that may be useful:

• Cell-based reporter assays: 0.1 nM–10 μM concentration range to establish potency and efficacy; incubations 6–24 h for reporter readout; maintain final DMSO ≤0.1–0.5% v/v.
• Biochemical binding/coactivator recruitment (TR-FRET/AlphaScreen): 0.01 nM–1 μM titrations depending on receptor LBD construct and tracer; buffers typically HEPES 25–50 mM, NaCl 100–150 mM, 0.01–0.05% detergent, pH 7.4–7.6.
• Thermal shift (DSF): 1–50 μM ligand with 1–5 μM THR LBD; observe ΔTm as evidence of binding.

These are general literature ranges and should be optimized for your system. Item-specific activity, solubility, and stability parameters are not specified; verify experimentally.

Safety and Handling

Authoritative safety information must be taken from the product SDS.

Item-specific hazard information 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 safety guidance for small-molecule research ligands (literature/general):

• PPE: Wear appropriate lab coat, safety glasses, and disposable nitrile gloves. Handle powders in a fume hood or ventilated enclosure to avoid inhalation/dermal exposure.
• Avoid aerosolization and contact with skin/eyes. Wash thoroughly after handling.
• Storage incompatibilities: Keep away from strong oxidizers and strong acids/bases unless compatibility is known. Protect from moisture and prolonged light exposure.
• Spill/accidental release: Avoid dust formation; carefully collect solid with dampened absorbent, dispose of in a sealed container per institutional hazardous waste protocols.
• First aid (overview; defer to SDS): Inhalation—move to fresh air; seek medical advice. Skin—wash with soap/water. Eyes—rinse cautiously with water for several minutes; remove contact lenses if present and easy to do. Ingestion—rinse mouth; seek medical attention.
• Environmental: Prevent release into drains; collect waste for proper disposal.

Special considerations:

• Bioactivity: As a receptor agonist, treat as potentially pharmacologically active; minimize exposure and prevent cross-contamination of bioassays.
• Dust control: If finely powdered, consider anti-static measures and weigh in a balance enclosure.

Solvent Selection

Item-specific solubility/solvent data: Not specified for this item; refer to CoA/Spec Sheet.

General solvent strategy for THR-β ligands (literature/general):

• Primary stock solvent: Anhydrous DMSO is the default due to broad solvency for lipophilic, aromatic agonists and excellent miscibility with aqueous buffers at low final %.
• Alternative stock solvents: DMF or ethanol can be used when DMSO is undesirable, noting different cytotoxicity thresholds in cell systems (e.g., keep DMF ≲0.5% v/v, ethanol ≲0.5–1% v/v as tolerated by specific cells).
• Aqueous delivery: Dilute DMSO stocks into pre-warmed assay buffer/media with vigorous mixing to a final DMSO concentration typically ≤0.1–0.5% v/v (literature guidance). Include matched vehicle controls.
• Surfactants: If precipitation occurs on dilution, 0.01–0.05% nonionic surfactant (e.g., Pluronic F-68) may aid solubilization in cell culture (check system compatibility).

Comparison (general considerations):

• DMSO: Highest solvency; can affect membrane properties and gene expression at >0.5–1%.
• Ethanol: Volatile; may perturb cells at modest %; generally less solvating for highly lipophilic chemotypes.
• PEG400: Useful for in vitro biochemical assays; viscosity complicates pipetting; may interfere with some readouts.

Practical tips:

• Pre-screen solubility at intended concentrations by visual inspection and light scattering if available.
• Use low-retention tips and glass vials for concentrated stocks to minimize adsorption.
• Filter through 0.22 μm PTFE if particulate is observed.

Storage and Reconstitution

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

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

Additional item-specific details (appearance, stabilizers, solvent, exact reconstitution): Not specified for this item; refer to CoA/Spec Sheet.

General reconstitution guidance for small-molecule THR-β agonists (literature/general):

• Upon receipt, allow the sealed container to equilibrate to room temperature before opening to prevent condensation.
• For solids: Dissolve in anhydrous DMSO to prepare a concentrated stock (e.g., 10–50 mM). For solutions: Confirm concentration and solvent on the label/CoA.
• Aliquot into low-bind, amber vials or microtubes to minimize freeze–thaw cycles and light exposure. Purge headspace with inert gas if long-term storage is anticipated.
• Storage of stocks: -20°C (or per CoA) is typical for DMSO stocks. Avoid repeated freeze–thaw; thaw only what is needed.
• Stability: If long-term studies are planned, establish in-house stability by LC–MS/HPLC after defined storage intervals and after multiple freeze–thaw cycles.

Working solution handling:

• Prepare fresh dilutions in assay buffer/media immediately before use.
• Maintain final DMSO within assay-acceptable limits and include vehicle controls.
• Discard any solutions showing precipitation, discoloration, or unexpected odor.

Disposal: Follow institutional guidelines for organic/chemical hazardous waste. Avoid release into drains.

Structure and Identity

Overview: THR-β agonist 1 is a small-molecule life-science research tool designed to activate the thyroid hormone receptor beta (THR-β; NR1A2), a ligand-activated nuclear transcription factor.

Item-specific identifiers (from Product Data):

• SKU: T1454532
• Product Name: THR-β agonist 1
• CAS: 2648403-17-0
• Storage Conditions: Store at -20°C
• Shipped In: Ice chest + Ice pads

Item-specific structure data: 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.
• SMILES: Not specified for this item; refer to CoA/Spec Sheet.
• InChIKey: Not specified for this item; refer to CoA/Spec Sheet.

General structural context (literature/general):

• THR ligands are commonly lipophilic, aromatic small molecules featuring iodine-free scaffolds in modern β-selective chemotypes, often incorporating heteroaromatics and H-bond acceptors/donors tuned for THR ligand-binding pocket interactions.
• Functional groups frequently include phenoxy/aryloxy motifs, amide/ether linkers, and polar end-groups to balance potency and permeability.

2D structural description (general):

• Typical THR-β agonists present a polyaromatic core with one or more heteroatoms positioned to engage the canonical THR binding cavity via hydrophobic contacts and a polar interaction network. Substitution patterns modulate β- versus α-subtype selectivity. Exact ring system(s) and stereochemistry for this item are not specified; consult CoA/Spec Sheet if required for structure-based work.

Synthetic Utility

Not typically applicable. THR-β agonist 1 is intended as a bioactive probe for receptor pharmacology rather than as a building block or reagent in organic synthesis.

General note (literature/general):

• If structural modification or derivatization is desired for SAR or probe development, medicinal chemistry teams commonly use parallel synthesis to explore substitutions on the aromatic/heteroaromatic scaffold, followed by biological profiling. However, the specific functional handles available on this item are not specified; consult CoA/Spec Sheet or request structural information to plan derivatizations.

For synthetic chemistry content relevant to this catalog entry, please refer instead to the “Biological Roles,” “Target Specificity,” and “Application Protocols” tabs, which better align with the intended use of this product.

Target Specificity

Item-specific target data (affinity, selectivity, EC50/IC50): Not specified for this item; refer to CoA/Spec Sheet or primary literature associated with the exact CAS (2648403-17-0) if available.

General target background (literature/general):

• Primary target: Thyroid hormone receptor beta (THR-β, NR1A2), a ligand-activated transcription factor that forms heterodimers with RXR and binds thyroid hormone response elements (TREs) to regulate transcription.
• Selectivity rationale: β-selective agonists are designed to preferentially activate THR-β over THR-α (NR1A1) by leveraging subtle differences in the ligand-binding pocket. Selectivity reduces confounding α-mediated responses in experimental systems.
• Readouts of specificity: Comparative reporter assays in cells expressing THR-α vs THR-β; coactivator recruitment profiles; binding studies with isolated LBDs; gene expression panels enriched for β-responsive transcripts.
• Off-target assessment: Nuclear receptor panel screens (e.g., PPARs, LXR, FXR, ERs) and broad binding assays help exclude cross-reactivity. Such profiling is assay- and scaffold-dependent.

Recommendations:

• Include THR-α counter-screens and vehicle controls in all studies.
• Establish concentration–response curves with at least 8–12 points across 3–4 logs of concentration.
• Report and compare Emax relative to a reference agonist (e.g., T3) within the same assay system.

Note: Without item-specific data, end-users should verify potency and selectivity under their experimental conditions.