ML-109 | CAS#1186649-91-1 | TSHR agonist

MedKoo Cat#: 555782 | Name: ML109

Description:

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

ML-109, also known as CID-25246343 and (S)-(+)-NCGC00161870, is a potent and full thyroid stimulating hormone receptor (TSHR) agonist. ML109 is the first selective and orally available small-molecule TSHR agonist, and the probe will be a useful pharmacological tool to study TSHR biology in thyroidal and extrathyroidal tissues

Chemical Structure

ML109

CAS#1186649-91-1 (free base)

Theoretical Analysis

MedKoo Cat#: 555782

Name: ML109

CAS#: 1186649-91-1 (free base)

Chemical Formula: C31H29N3O5

Exact Mass: 523.2107

Molecular Weight: 523.59

Elemental Analysis: C, 71.11; H, 5.58; N, 8.03; O, 15.28

Price and Availability

Size	Price	Availability
10mg	USD 150.00	Ready to ship
25mg	USD 250.00	Ready to ship
50mg	USD 450.00	Ready to ship
100mg	USD 750.00	Ready to ship
200mg	USD 1,350.00	Ready to ship
500mg	USD 2,950.00	Ready to ship

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Related CAS #

ML109 HCl 1186649-91-1 (free base)

Synonym

ML-109; ML 109; ML109; CID-25246343; CID 25246343; CID25246343; (S)-(+)-NCGC00161870; NCGC-00161870; NCGC 00161870;

IUPAC/Chemical Name

N-(4-((5-(3-benzyl-5-hydroxy-4-oxo-1,2,3,4-tetrahydroquinazolin-2-yl)-2-methoxybenzyl)oxy)phenyl)acetamide

InChi Key

JRVXFGNCHKHBPA-UHFFFAOYSA-N

InChi Code

InChI=1S/C31H29N3O5/c1-20(35)32-24-12-14-25(15-13-24)39-19-23-17-22(11-16-28(23)38-2)30-33-26-9-6-10-27(36)29(26)31(37)34(30)18-21-7-4-3-5-8-21/h3-17,30,33,36H,18-19H2,1-2H3,(H,32,35)

SMILES Code

CC(NC1=CC=C(OCC2=CC(C(N3CC4=CC=CC=C4)NC5=C(C(O)=CC=C5)C3=O)=CC=C2OC)C=C1)=O

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

2934.99.9001

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 increase in cyclic adenosine 3′, 5′ monophosphate (cAMP).

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#T21D06P19

QC Data

View QC data: current batch, Lot#T21D06P19

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

ML-109 is a potent and full thyroid stimulating hormone receptor (TSHR) agonist with an EC50 of 40 nM

In vitro activity:

The effects of CID-25246343/ML109 or TSH on cAMP accumulation in cells expressing TSHR, TSHR-KFLR in which the large amino-terminal ectodomain to which TSH binds, is deleted, or N5.47A in which Asn at position-5.47 was mutated to Ala. Docking of CID-25246343/ML109 into the homology model of TSHR predicts CID-25246343/ML109 binds within the transmembrane helical bundlen (left panel). Enlargement of the boxed region in the left panel (right panel) shows an interaction of CID-25246343/ML109 with an Asn in TMH5 (N5.47). CID-25246343/ML109 activates TSHR by binding to the transmembrane helical bundle. Reference: National Center for Biotechnology Information (US); 2010. https://pubmed.ncbi.nlm.nih.gov/21735603/

In vivo activity:

Vehicle (PEG 300, control) or CID-25246343/ML109 (2.5 mg) was given by esophageal gavage and serum T4 was measured 2 hr later. Vehicle (control) or CID-25246343/ML109 (2.5 mg) was given by esophageal gavage on days 1 and 2. On the morning of the 3rd day, Na125I (20 μCi) was administered by esophageal gavage and the mice were sacrificed 2 hr later. The thyroid glands and small pieces of liver were excised and counted for 125I radioactivity. These in vivo studies (Figure 6) showed that CID25246343/ML109 could increase secretion of T4 and thyroidal iodide uptake in mice after administration by esophageal gavage, suggesting CID-25246343/ML109 is an orally available small molecule that can stimulate thyroid gland function1. Reference: National Center for Biotechnology Information (US); 2010. https://pubmed.ncbi.nlm.nih.gov/21735603/

	Solvent	mg/mL	mM	comments
Solubility
	DMSO	83.0	158.50

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 523.59 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. Titus S, Huang W, Marugan J, Southall N, Inglese J, Austin C, Zheng W, Englund E, Neumann S, Gershengorn M. Identification of Potent and Selective Thyroid Stimulating Hormone Receptor Agonists. 2009 Sep 1 [updated 2011 Mar 25]. In: Probe Reports from the NIH Molecular Libraries Program [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2010–. PMID: 21735603.

In vitro protocol:

In vivo protocol:

Titus S, Huang W, Marugan J, et al. Identification of Potent and Selective Thyroid Stimulating Hormone Receptor Agonists. In: Probe Reports from the NIH Molecular Libraries Program. Bethesda (MD): National Center for Biotechnology Information (US); 2010.