ML-109 (CID-25246343) is a novel, potent and full thyroid stimulating hormone receptor (TSHR) agonist with an EC50 of 40 nM. This small-molecule TSHR agonist is the first to be available orally, and as such, it will serve as a valuable pharmacological tool for researching the biology of TSHR in thyroid and extrathyroidal tissues.

Physicochemical Properties

Molecular Formula	C31H29N3O5
Molecular Weight	523.57906794548
Exact Mass	523.21
Elemental Analysis	C, 71.11; H, 5.58; N, 8.03; O, 15.28
CAS #	1186649-91-1
Related CAS #	ML109 HCl; 1186649-91-1
PubChem CID	25246343
Appearance	White to light yellow solid powder
LogP	5.1
Hydrogen Bond Donor Count	3
Hydrogen Bond Acceptor Count	6
Rotatable Bond Count	8
Heavy Atom Count	39
Complexity	812
Defined Atom Stereocenter Count	0
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)
Chemical Name	N-[4-[[5-(3-benzyl-5-hydroxy-4-oxo-1,2-dihydroquinazolin-2-yl)-2-methoxyphenyl]methoxy]phenyl]acetamide
Synonyms	ML-109; ML 109; ML109; CID-25246343; CID 25246343; CID25246343
HS Tariff Code	2934.99.9001
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)

Biological Activity

Targets	TSHR ( EC50 = 40 nM )
ln Vitro	ML-109 (Compound 2) exhibits no activity at FSHR or LHCGR, similar to compound 1, and is a full agonist at TSHR with an EC50 of 40 nM. There is a functional group in ML-109 called an aminal that can be broken down by hydrolysis or other processes. It has been observed that ML-109 degrades at low pH (t1/2 of ~3 h), but it is surprisingly stable at neutral and basic conditions (t1/2 of ~16 h)[1].
References	[1]. Small-molecule agonists for the thyrotropin receptor stimulate thyroid function in human thyrocytes and mice. Proc Natl Acad Sci U S A. 2009 Jul 28;106(30):12471-6.
Additional Infomation	N-[4-[[5-[5-hydroxy-4-oxo-3-(phenylmethyl)-1,2-dihydroquinazolin-2-yl]-2-methoxyphenyl]methoxy]phenyl]acetamide is a member of quinazolines.

Solubility Data

Solubility (In Vitro)

DMSO: ~83.3 mg/mL (~159.2 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.17 mg/mL (4.14 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 21.7 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: ≥ 2.17 mg/mL (4.14 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in 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 21.7 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 3: ≥ 2.17 mg/mL (4.14 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 21.7 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	1.9099 mL	9.5496 mL	19.0993 mL
	5 mM	0.3820 mL	1.9099 mL	3.8199 mL
	10 mM	0.1910 mL	0.9550 mL	1.9099 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.