ML224 | CAS#1338824-21-7 | TSH-stimulated cAMP inhibitor

MedKoo Cat#: 555345 | Name: ML224

Description:

WARNING: This product is for research use only, not for human or veterinary use.

ML224, also known as NCGC00242364 and ANTAG3, is a selective TSHR inverse agonist; inhibits TSH-stimulated cAMP production with an IC50 = 2.3 μM. ML224 could be a useful tool for studying TSHR functions; it could also be a potential lead for development of drugs to treat TSHR-mediated hyperthyroidism caused by constitutively activating mutations or stimulating auto-antibodies associated with Graves’ disease.

Chemical Structure

ML224

CAS#1338824-21-7

Theoretical Analysis

MedKoo Cat#: 555345

Name: ML224

CAS#: 1338824-21-7

Chemical Formula: C31H31N3O5

Exact Mass: 525.2264

Molecular Weight: 525.61

Elemental Analysis: C, 70.84; H, 5.95; N, 7.99; O, 15.22

Price and Availability

Size	Price	Availability
5mg	USD 150.00	Ready to ship
10mg	USD 250.00	Ready to ship
25mg	USD 450.00	Ready to ship
50mg	USD 750.00	Ready to ship
100mg	USD 1,150.00	Ready to ship
200mg	USD 1,950.00	2 Weeks

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Synonym

ML224; ML-224; ML 224; NCGC00242364; NCGC-00242364; NCGC 00242364; ANTAG3; ANTAG-3; ANTAG 3;

IUPAC/Chemical Name

N-(4-((5-(3-(furan-2-ylmethyl)-4-oxo-1,2,3,4-tetrahydroquinazolin-2-yl)-2-methoxybenzyl)oxy)-3,5-dimethylphenyl)acetamide

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)

SMILES Code

COC(C(COC1=C(C)C=C(NC(C)=O)C=C1C)=C2)=CC=C2C(NC3=C4C=CC=C3)N(C4=O)CC5=CC=CO5

Appearance

Solid powder

Purity

>98% (or refer to the Certificate of Analysis)

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

Soluble in DMSO

Shelf Life

>3 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.03.00

More Info

Thyroid Stimulating Hormone (TSH) is a heterodimeric glycoprotein hormone that regulates thyroid homeostasis upon interaction with the TSH receptor (TSHR). TSH binds to the TSH receptor, which couples preferentially to the G-alpha (s) (Gs) protein, resulting in activation of adenylate cyclase and an increase in cyclic adenosine 3′, 5′ monophosphate (cAMP).

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#A23T05K29

QC Data

View QC data: current batch, Lot#A23T05K29

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

ML224 (NCGC00242364) is a selective TSHR antagonist with an IC50 value of 2.1 µM.

In vitro activity:

TSH and IGF-1 receptor antagonists were used to probe TSH/IGF-1 receptor crosstalk in primary cultures of Graves' orbital fibroblasts (GOFs) following activation with monoclonal TSH receptor antibody, M22. Inhibition of HA secretion following TSH receptor stimulation was measured by modified HA elisa. TSH receptor antagonist, ANTAG3 (NCGC00242364), inhibited both IGF-1 receptor -dependent and -independent pathways at all doses of M22; whereas IGF-1 receptor antagonists linsitinib and 1H7 (inhibitory antibody) lost efficacy at high M22 doses. Reference: Br J Pharmacol. 2017 Feb;174(4):328-340. https://pubmed.ncbi.nlm.nih.gov/27987211/

In vivo activity:

This study tested the in vivo activity of ANTAG3 by measuring its effects to lower serum free T4 and thyroid gene expression in female BALB/c mice continuously treated with ANTAG3 for 3 days and given low doses of TRH continuously or stimulated by a single administration of a monoclonal thyroid-stimulating antibody M22. ANTAG3 was selective for TSHR inhibition; half-maximal inhibitory doses were 2.1 μM for TSHR and greater than 30 μM for LH and FSH receptors. In mice treated with TRH, ANTAG3 lowered serum free T4 by 44% and lowered mRNAs for sodium-iodide cotransporter and thyroperoxidase by 75% and 83%, respectively. In mice given M22, ANTAG3 lowered serum free T4 by 38% and lowered mRNAs for sodium-iodide cotransporter and thyroperoxidase by 73% and 40%, respectively. Reference: Endocrinology. 2014 Jan;155(1):310-4. https://pubmed.ncbi.nlm.nih.gov/24169564/

	Solvent	mg/mL	mM	comments
Solubility
	DMSO	100.0	190.26

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 525.61 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

1. Place RF, Krieger CC, Neumann S, Gershengorn MC. Inhibiting thyrotropin/insulin-like growth factor 1 receptor crosstalk to treat Graves' ophthalmopathy: studies in orbital fibroblasts in vitro. Br J Pharmacol. 2017 Feb;174(4):328-340. doi: 10.1111/bph.13693. Epub 2017 Jan 27. PMID: 27987211; PMCID: PMC5289943. 2. Neumann S, Nir EA, Eliseeva E, Huang W, Marugan J, Xiao J, Dulcey AE, Gershengorn MC. A selective TSH receptor antagonist inhibits stimulation of thyroid function in female mice. Endocrinology. 2014 Jan;155(1):310-4. doi: 10.1210/en.2013-1835. Epub 2013 Dec 4. PMID: 24169564; PMCID: PMC3868809.

In vitro protocol:

In vivo protocol:

1. Neumann S, Nir EA, Eliseeva E, Huang W, Marugan J, Xiao J, Dulcey AE, Gershengorn MC. A selective TSH receptor antagonist inhibits stimulation of thyroid function in female mice. Endocrinology. 2014 Jan;155(1):310-4. doi: 10.1210/en.2013-1835. Epub 2013 Dec 4. PMID: 24169564; PMCID: PMC3868809.

1: Gong S, Zeng Y, Wang Z, Li Y, Wu R, Li L, Hu H, Qin P, Yu Z, Huang X, Guo P, Yang H, He Y, Zhao Z, Xiao W, Zhao X, Gao L, Cai S, Zeng Z. Intestinal deguelin drives resistance to acetaminophen-induced hepatotoxicity in female mice. Gut Microbes. 2024 Jan-Dec;16(1):2404138. doi: 10.1080/19490976.2024.2404138. Epub 2024 Sep 21. PMID: 39305468; PMCID: PMC11418218. 2: Huang W, Englund E, Titus S, Southall N, Zheng W, Ferrer M, Marugan J, Neumann S, Gershengorn M. Identification of Thyroid Stimulating Hormone Receptor Inverse Agonists. 2011 Mar 31 [updated 2013 Feb 28]. In: Probe Reports from the NIH Molecular Libraries Program [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2010–. PMID: 23658967. 3: Bartko PE, Heitzinger G, Spinka G, Pavo N, Prausmüller S, Kastl S, Winter MP, Arfsten H, Tan TC, Gebhard C, Mascherbauer J, Hengstenberg C, Strunk G, Hülsmann M, Goliasch G. Principal Morphomic and Functional Components of Secondary Mitral Regurgitation. JACC Cardiovasc Imaging. 2021 Dec;14(12):2288-2300. doi: 10.1016/j.jcmg.2021.05.020. Epub 2021 Jul 14. PMID: 34274262.