TSHR antagonist S37a is a selective thyroid stimulating hormone receptor TSHR antagonist (inhibitor) with potential for studying Graves' orbitopathy.

Physicochemical Properties

Molecular Formula	C25H19N2O3S2
Molecular Weight	459.5600
Exact Mass	460.091
CAS #	2143452-20-2
Related CAS #	TSHR antagonist S37b;2143452-22-4
PubChem CID	132083268
Appearance	Off-white to light yellow solid powder
LogP	3.8
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	5
Rotatable Bond Count	2
Heavy Atom Count	32
Complexity	907
Defined Atom Stereocenter Count	7
SMILES	S1C2=C([C](C3C([H])=C([H])C([H])=C([H])C=3[H])[C@@]3([H])[C@]1([H])[C@@]1([H])C([H])([H])[C@]3([H])[C@@]3([H])C(N(C4C([H])=C([H])C([H])=C([H])C=4[H])C([C@@]13[H])=O)=O)SC(N2[H])=O |^1:3|
InChi Key	YGFJFPYQZCZNIH-HSXTZPDUSA-N
InChi Code	InChI=1S/C25H20N2O3S2/c28-23-18-14-11-15(19(18)24(29)27(23)13-9-5-2-6-10-13)20-17(14)16(12-7-3-1-4-8-12)21-22(31-20)26-25(30)32-21/h1-10,14-20H,11H2,(H,26,30)/t14-,15-,16-,17-,18+,19-,20-/m0/s1
Chemical Name	(1S,2S,9R,10S,11R,12R,16R)-9,14-diphenyl-3,7-dithia-5,14-diazapentacyclo[9.5.1.02,10.04,8.012,16]heptadec-4(8)-ene-6,13,15-trione
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

ln Vitro	TSHR is inhibited by the TSHR antagonist S37a. The half-life of mTSHR and hTSHR in HEK293 cells is 40 µM and roughly 20 µM, respectively [1]. The TSHR antagonist S37a blocks not only the thyrotropin-induced activation of TSHR but also the activation of the allosteric small molecule agonist C2, the human monoclonal TSAb M22, and the mouse monoclonal KSAb1 [1].
ln Vivo	The TSHR antagonist S37a also inhibits cyclic adenosine monophosphate production via an oligoclonal TSAb that is substantially abundant in the sera of GO patients [1]. The TSHR antagonist S37a (10 mg/kg; ig) demonstrates no toxicity in mice and has an oral bioavailability of up to 53% [1].
Animal Protocol	Animal/Disease Models: SWISS (CD1) mice (38-43 g) [1] Doses: 10 mg/kg Route of Administration: po (oral gavage) Experimental Results: Oral bioavailability is as high as 53%, and the half-life after oral administration is 2.9 hrs (hrs (hours)).
References	[1]. A New Highly Thyrotropin Receptor-Selective Small-Molecule Antagonist with Potential for the Treatment of Graves' Orbitopathy. Thyroid. 2019 Jan;29(1):111-123.

Solubility Data

Solubility (In Vitro)

DMSO : ~100 mg/mL (~217.12 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (5.43 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 (5.43 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 ultrasonication. 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 3: ≥ 2.5 mg/mL (5.43 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	2.1760 mL	10.8800 mL	21.7599 mL
	5 mM	0.4352 mL	2.1760 mL	4.3520 mL
	10 mM	0.2176 mL	1.0880 mL	2.1760 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.