| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 2mg |
|
||
| 5mg |
|
||
| 10mg |
|
||
| 25mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| Other Sizes |
|
Purity: ≥98%
ML224, also known as NCGC00242364 and ANTAG3, is a selective and inverse agonist of Thyroid Stimulating Hormone Receptor(TSHR). It suppresses the synthesis of cAMP stimulated by TSH with an IC50 of 2.3 μM. With a half-maximum inhibitory dose of 2.1 μM for TSHR and more than 30 μM for LH and FSH receptors, ANTAG3 was selectively inhibiting TSHR. ANTAG3 reduced sodium-iodide cotransporter and thyroperoxidase mRNAs by 75% and 83%, respectively, and serum free T4 by 44% in mice receiving TRH treatment. ANTAG3 reduced serum free T4 by 38% and thyroperoxidase and sodium-iodide cotransporter mRNAs by 73% and 40%, respectively, in mice administered M22. We have, in summary, created a selective TSHR antagonist that works well in vivo in mice. This could result in the development of a medication to treat Graves' disease, as it is the first report of a small-molecule TSHR antagonist that is active in vivo. Additionally, ML224 may provide a path for the creation of medications to treat TSHR-mediated hyperthyroidism, which is brought on by constitutively activating mutations or inducing auto-antibodies linked to Graves' disease.
| Targets |
TSHR ( IC50 = 2.1 μM ); LHR ( IC50 ＞ 30 μM ); FSHR ( IC50 ＞ 30 μM )
|
|
|---|---|---|
| ln Vitro |
|
|
| ln Vivo |
|
|
| Enzyme Assay |
ML224, also known as NCGC00242364 and ANTAG3, is a selective and inverse agonist of Thyroid Stimulating Hormone Receptor(TSH)R). With an IC50 of 2.3 μM, it suppresses the production of cAMP stimulated by TSH. TSHR inhibition was the only pathway that ANTAG3 was selective for, with half-maximum inhibitory doses for TSHR being 2.1 μM and for LH and FSH receptors being greater than 30 μM.
|
|
| Cell Assay |
Cell Line: Human embryonic kidney 293 cells (stably expressing TSHRs, LHRs, or FSHRs)
Concentration: 0.001-100 µM Incubation Time: 20 min Result: Showed the IC50 for stimulation by bovine TSH (1.8 nM) was 2.1 µM. Showed inhibition of LH and FSH stimulation was less than 15% for LH (1 nM) and less than 30% for FSH (1 nM) at 30 µM. |
|
| Animal Protocol |
Female BALB/c mice (8 to 13-week-old; ~18.7 g)
Dosage: 2 mg/mice Intraperitoneal injection via osmotic pump; single daily for 3 days |
|
| References | ||
| Additional Infomation |
N-[4-[[5-[3-(2-furanylmethyl)-4-oxo-1,2-dihydroquinazolin-2-yl]-2-methoxyphenyl]methoxy]-3,5-dimethylphenyl]acetamide is a member of quinazolines.
|
| Molecular Formula |
C31H31N3O5
|
|
|---|---|---|
| Molecular Weight |
525.59
|
|
| Exact Mass |
525.226
|
|
| Elemental Analysis |
C, 70.84; H, 5.95; N, 7.99; O, 15.22
|
|
| CAS # |
1338824-21-7
|
|
| Related CAS # |
|
|
| PubChem CID |
50897809
|
|
| Appearance |
White to off-white solid powder
|
|
| Density |
1.3±0.1 g/cm3
|
|
| Boiling Point |
752.3±60.0 °C at 760 mmHg
|
|
| Flash Point |
408.8±32.9 °C
|
|
| Vapour Pressure |
0.0±2.5 mmHg at 25°C
|
|
| Index of Refraction |
1.626
|
|
| LogP |
2.92
|
|
| Hydrogen Bond Donor Count |
2
|
|
| Hydrogen Bond Acceptor Count |
6
|
|
| Rotatable Bond Count |
8
|
|
| Heavy Atom Count |
39
|
|
| Complexity |
829
|
|
| Defined Atom Stereocenter Count |
0
|
|
| SMILES |
CC(NC1=CC(C)=C(OCC2=CC(C(N3CC4=CC=CO4)NC5=C(C=CC=C5)C3=O)=CC=C2OC)C(C)=C1)=O
|
|
| InChi Key |
BFTSWGYWHRJVNI-UHFFFAOYSA-N
|
|
| InChi Code |
InChI=1S/C31H31N3O5/c1-19-14-24(32-21(3)35)15-20(2)29(19)39-18-23-16-22(11-12-28(23)37-4)30-33-27-10-6-5-9-26(27)31(36)34(30)17-25-8-7-13-38-25/h5-16,30,33H,17-18H2,1-4H3,(H,32,35)
|
|
| Chemical Name |
N-[4-[[5-[3-(furan-2-ylmethyl)-4-oxo-1,2-dihydroquinazolin-2-yl]-2-methoxyphenyl]methoxy]-3,5-dimethylphenyl]acetamide
|
|
| Synonyms |
|
|
| HS Tariff Code |
2934.99.03.00
|
|
| 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)
|
| Solubility (In Vitro) |
|
|||
|---|---|---|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.76 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 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. Solubility in Formulation 2: ≥ 2.5 mg/mL (4.76 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 | 1.9026 mL | 9.5131 mL | 19.0262 mL | |
| 5 mM | 0.3805 mL | 1.9026 mL | 3.8052 mL | |
| 10 mM | 0.1903 mL | 0.9513 mL | 1.9026 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.
ANTAG3 structure and selectivity.Endocrinology.2014 Jan;155(1):310-4. |
|---|
 ANTAG3 lowers serum FT4 levels and thyroidal mRNAs for TPO and NIS in mice continuously stimulated by TRH. A, TRH (2.4 μg/d for 3 d) was administered ip via osmotic pump with or without ANTAG3 (2 mg/d). The animals were euthanized on day 4. B, Serum FT4 levels. C, mRNA levels of TPO and NIS in thyroid gland lysates.Endocrinology.2014 Jan;155(1):310-4. |
 ANTAG3 lowers serum FT4 levels and thyroidal mRNAs for TPO and NIS in mice stimulated by a single injection of M22. A, T3(5 μg/d for 4 d) was administered by daily ip injection, and ANTAG3 was given for 3 days (2 mg/d) via an osmotic pump. On day 4, the animals were given an ip injection of vehicle or ANTAG3 (2 mg) and 4 hours later an ip injection of M22 (0.5 μg) or vehicle.Endocrinology.2014 Jan;155(1):310-4. |
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
COA
