| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| Other Sizes |
| Targets |
IC50: 55 nM (THR)[1]
NH-3 targets the thyroid hormone receptor (THR). As an antagonist, it inhibits the binding of thyroid hormones to their respective receptors, resulting in hindered cofactor recruitment. The compound is a derivative of the selective thyromimetic GC-1. It is valuable for studying epigenetic regulation, transcriptional control, and oncogenesis, particularly in cancers dependent on p300/CBP activity. Its potency and selectivity make it an important tool for investigating histone acetyltransferase–targeted therapeutic strategies. |
|---|---|
| ln Vitro |
In vitro, NH-3 demonstrates potent THR antagonism with an IC₅₀ of 55 nM. It effectively inhibits the binding of thyroid hormones to their receptors. The compound is used in biochemical and cell-based assays to study thyroid hormone signaling and transcriptional regulation. Its potency and selectivity make it suitable for investigating p300/CBP-dependent cancers. The compound is a click chemistry reagent, enabling bioconjugation applications.
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| ln Vivo |
Heart rate was somewhat lowered by NH3 (46.2-27, 700 nmol/kg/day; 7 days); however, the effect vanished at >2920 nmol/kg/day. At 46.2 nmol/kg/day, NH3 has no influence on T3's ability to decrease cholesterol; but, at 924 nmol/kg/day, it inhibits tachycardia and TSH inhibition [2].
In vivo, NH-3 is orally active. At doses of 46.2-27,700 nmol/kg/day over 7 days, it moderately reduces heart rate starting at 46.2 nmol/kg/day, but this effect disappears at >2,920 nmol/kg/day. NH-3 has no effect on the cholesterol-lowering action of 46.2 nmol/kg/day T3, but it inhibits tachycardia and TSH suppression up to 924 nmol/kg/day. These data demonstrate its in vivo pharmacological effects on thyroid hormone-mediated responses. |
| Enzyme Assay |
Non-cell-based enzyme/receptor binding assays for NH-3 typically involve competitive binding studies using purified thyroid hormone receptor (THR) protein. Standard protocols include incubating varying concentrations of the test compound with the THR ligand-binding domain and a radiolabeled thyroid hormone (e.g., [¹²⁵I]-T3) in appropriate buffer systems, followed by separation of bound from free ligand via filtration or charcoal adsorption. Binding affinity (IC₅₀ values) is calculated using nonlinear regression analysis. The compound shows an IC₅₀ of 55 nM. Surface plasmon resonance (SPR) may also be employed.
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| Cell Assay |
Cell-based assays for NH-3 typically utilize cell lines expressing thyroid hormone receptors (THR) and a luciferase reporter gene. Standard protocols involve culturing cells in appropriate media at 37°C in 5% CO₂, followed by treatment with varying concentrations of the compound (typically 0.01-10 μM) and thyroid hormone (T3) for 18-24 hours. Reporter gene activity is quantified by luminescence. The compound's ability to inhibit T3-induced transcriptional activation is assessed. IC₅₀ values are calculated from dose-response curves. The compound is also used in p300/CBP activity assays.
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| Animal Protocol |
In vivo animal studies for NH-3 typically involve oral administration in rodent models (mice or rats). Standard protocols include dosing at ranges of 46.2-27,700 nmol/kg/day over 7 days. Pharmacodynamic assessments may include heart rate measurement, serum cholesterol analysis, TSH levels, and monitoring of body weight and general health parameters. NH-3 moderately reduces heart rate starting at 46.2 nmol/kg/day but this effect disappears at >2,920 nmol/kg/day. It has no effect on T3-induced cholesterol lowering but inhibits tachycardia and TSH suppression up to 924 nmol/kg/day.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties for NH-3 are consistent with an orally active small molecule. The compound has a molecular weight of 473.52 g/mol and shows solubility in DMSO (95 mg/mL). For in vivo administration, formulations using 10% DMSO + 40% PEG300 + 5% Tween 80 + 45% Saline (3.3 mg/mL) are recommended. The compound should be stored at low temperature; powder at -20°C for up to 3 years or in solvent at -80°C for 1 year. Definitive PK parameters require formal studies.
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| References |
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| Additional Infomation |
Triiodothyronine inhibitor; structure described in the first article.
NH-3 is a potent, orally active, reversible thyroid hormone receptor (THR) antagonist with an IC₅₀ of 55 nM. It is a derivative of the selective thyromimetic GC-1 and inhibits thyroid hormone binding and cofactor recruitment. The compound is valuable for studying epigenetic regulation, transcriptional control, and oncogenesis, particularly in cancers dependent on p300/CBP activity. It is a click chemistry reagent. It is not an approved drug and has not undergone clinical trials. |
| Molecular Formula |
C28H27NO6
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|---|---|
| Molecular Weight |
473.52
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| Exact Mass |
473.183
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| CAS # |
447415-26-1
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| PubChem CID |
10027822
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| Appearance |
Light yellow to green yellow solid powder
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| LogP |
6.8
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
8
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| Heavy Atom Count |
35
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| Complexity |
774
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| Defined Atom Stereocenter Count |
0
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| SMILES |
OC1C(C#CC2C=CC([N+]([O-])=O)=CC=2)=CC(CC2C(C)=CC(OCC(O)=O)=CC=2C)=CC=1C(C)C
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| InChi Key |
IXMROOKFPWGDGF-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C28H27NO6/c1-17(2)25-14-21(15-26-18(3)11-24(12-19(26)4)35-16-27(30)31)13-22(28(25)32)8-5-20-6-9-23(10-7-20)29(33)34/h6-7,9-14,17,32H,15-16H2,1-4H3,(H,30,31)
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| Chemical Name |
2-[4-[[4-hydroxy-3-[2-(4-nitrophenyl)ethynyl]-5-propan-2-ylphenyl]methyl]-3,5-dimethylphenoxy]acetic acid
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO: 100 mg/mL (211.18 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.28 mM) (saturation unknown) in 10% DMSO + 40% PEG300 +5% Tween-80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 + to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1118 mL | 10.5592 mL | 21.1184 mL | |
| 5 mM | 0.4224 mL | 2.1118 mL | 4.2237 mL | |
| 10 mM | 0.2112 mL | 1.0559 mL | 2.1118 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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