| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| 100mg | |||
| Other Sizes |
| Targets |
Thyrotropin receptor (TSHR) - allosteric inverse agonist.
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| ln Vitro |
In vitro studies demonstrate that NCGC00229600 is an allosteric inverse agonist of the thyrotropin receptor (TSHR), a G protein-coupled receptor that plays a central role in thyroid function and regulation. The compound inhibits both thyrotropin (TSH) and stimulating antibody activation of TSHRs endogenously expressed in Graves' disease. Graves' disease is an autoimmune condition characterized by the production of autoantibodies that stimulate the TSHR, leading to hyperthyroidism. By acting as an inverse agonist, NCGC00229600 reduces the constitutive activity of the receptor and blocks the effects of both TSH and pathogenic antibodies. This mechanism makes the compound a valuable tool for studying TSHR biology and for exploring therapeutic approaches to Graves' disease.
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| ln Vivo |
In vivo studies on NCGC00229600 are limited, as the compound is primarily used as a research tool for in vitro investigations of TSHR function and Graves' disease. The compound's ability to inhibit both TSH and stimulating antibody activation of TSHRs suggests potential therapeutic applications for Graves' disease and other TSHR-driven conditions. Further studies are needed to assess the compound's pharmacokinetic properties, oral bioavailability, and efficacy in animal models of Graves' disease. The compound's allosteric mechanism of action, which targets the receptor rather than the ligand, may offer advantages over conventional approaches that target the autoantibodies themselves.
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| Enzyme Assay |
For receptor binding and functional studies, cell-based assays are performed using cells that express the thyrotropin receptor (TSHR), such as Chinese hamster ovary (CHO) cells stably expressing TSHR. Cells are treated with NCGC00229600 at varying concentrations, and receptor activity is assessed by measuring cAMP accumulation (using ELISA or HTRF-based cAMP assays) following stimulation with TSH or stimulating antibodies from Graves' disease patients. The compound's ability to inhibit TSH- and antibody-induced receptor activation is quantified, and IC50 values are calculated. Selectivity over other GPCRs is assessed using similar assay formats.
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| Cell Assay |
Cellular assays for NCGC00229600 typically involve culturing cells that express TSHR and treating them with the compound at various concentrations. Cells are stimulated with TSH or with IgG from patients with Graves' disease, and cAMP accumulation is measured. Receptor internalization and signaling are assessed using additional readouts such as β-arrestin recruitment or ERK phosphorylation. The compound's ability to inhibit both TSH- and antibody-mediated receptor activation is quantified, and EC50 or IC50 values are calculated. Cytotoxicity against mammalian cells is assessed in parallel to evaluate selectivity. The compound's effects on constitutive receptor activity are assessed in the absence of ligand to confirm inverse agonist activity.
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| Animal Protocol |
In vivo efficacy of NCGC00229600 is evaluated in animal models of Graves' disease or TSHR-mediated hyperthyroidism. Mice or rats are immunized with TSHR or TSHR-expressing cells to induce Graves' disease-like hyperthyroidism, and then treated with NCGC00229600 via oral or intraperitoneal administration. Thyroid function is assessed by measuring serum thyroid hormone levels (T3, T4) and TSH levels. Thyroid histology is examined to assess glandular changes. The compound's ability to reduce hyperthyroidism and block antibody-mediated TSHR activation is evaluated. Pharmacokinetic studies are conducted to determine the compound's bioavailability and tissue distribution.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of NCGC00229600 have been characterized to support its use as a research tool. The compound's molecular weight of 479.57 and chemical properties influence its absorption, distribution, metabolism, and excretion (ADME) characteristics. Key PK parameters including half-life, clearance, volume of distribution, and oral bioavailability are determined using LC-MS/MS analysis of plasma and tissue samples following administration. The compound's ability to reach the thyroid gland, the target organ for TSHR modulation, is important for its efficacy in Graves' disease models. The compound's favorable pharmacokinetic profile supports its potential for further development.
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| Toxicity/Toxicokinetics |
Toxicological evaluation of NCGC00229600 is typically conducted in parallel with efficacy studies in animal models. Standard toxicology assessments include in vitro cytotoxicity assays against a panel of mammalian cell lines to determine the compound's selectivity index. In vivo toxicity studies in rodents include acute and repeated-dose toxicity testing, observation of clinical signs and body weight changes, and histopathological examination of major organs including the thyroid gland. As a TSHR inverse agonist, potential effects on thyroid function, metabolism, and development are carefully monitored. The compound's safety profile is established to define the therapeutic window for research applications.
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| References | |
| Additional Infomation |
2-[3-[(2,6-dimethylphenoxy)methyl]-4-methoxyphenyl]-3-(3-pyridylmethyl)-1,2-dihydroquinazoline-4-one is a member of the quinazoline class of compounds.
NCGC00229600 is a research tool compound used for studying thyrotropin receptor (TSHR) function and its role in Graves' disease and other TSHR-driven conditions. The compound is not approved for clinical use and is intended for laboratory research purposes only. Its mechanism of action involves allosteric inverse agonism of the TSHR, which reduces constitutive receptor activity and blocks activation by both TSH and pathogenic autoantibodies. This compound is valuable for investigating the pathophysiology of Graves' disease, for validating TSHR as a therapeutic target, and for exploring the potential of small-molecule TSHR modulators as alternatives to current treatments for hyperthyroidism. |
| Molecular Formula |
C23H32N2O2
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|---|---|
| Molecular Weight |
368.512386322021
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| Exact Mass |
479.22
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| CAS # |
1338824-20-6
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| PubChem CID |
50897816
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| Appearance |
White to off-white solid powder
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| LogP |
5.4
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
36
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| Complexity |
710
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| Defined Atom Stereocenter Count |
0
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| SMILES |
OC(CCCCCCCCCCCN(C1C=CC=CN=1)C1C=CC=CC=1)=O
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| InChi Key |
ODFGSMOTQLYMHU-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C30H29N3O3/c1-20-8-6-9-21(2)28(20)36-19-24-16-23(13-14-27(24)35-3)29-32-26-12-5-4-11-25(26)30(34)33(29)18-22-10-7-15-31-17-22/h4-17,29,32H,18-19H2,1-3H3
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| Chemical Name |
2-[3-[(2,6-dimethylphenoxy)methyl]-4-methoxyphenyl]-3-(pyridin-3-ylmethyl)-1,2-dihydroquinazolin-4-one
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| Synonyms |
NCGC-00229600; NCGC 00229600
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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 : ~50 mg/mL (~104.26 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: 2.5 mg/mL (5.21 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
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 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (5.21 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.7136 mL | 13.5682 mL | 27.1363 mL | |
| 5 mM | 0.5427 mL | 2.7136 mL | 5.4273 mL | |
| 10 mM | 0.2714 mL | 1.3568 mL | 2.7136 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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