TSHR antagonist S37a

• CAT Number: I017555
• CAS Number: 2143452-20-2
• Molecular Formula: C25H20N2O3S2
• Molecular Weight: 460.57
• Purity: ≥95%
• Synonyms: (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
• InChI: 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
• InChIKey: YGFJFPYQZCZNIH-HSXTZPDUSA-N
• SMILES: C1C2C3C(C1C4C2C(=O)N(C4=O)C5=CC=CC=C5)SC6=C(C3C7=CC=CC=C7)SC(=O)N6

TSHR antagonist S37a is a highly selective thyrotropin receptor (TSHR) antagonist, with potential for the treatment of Graves’ orbitopathy[1].
TSHR antagonist S37a exhibits inhibition activity for TSHR, with IC50s of 40 µM and approximately 20 µM for mTSHR and hTSHR, respectively, in HEK293 cells[1].
TSHR antagonist S37a not only inhibits the TSHR activation by thyrotropin itself but also activation by monoclonal TSAb M22 (human), KSAb1 (murine), and the allosteric small-molecule agonist C2[1].
TSHR antagonist S37a also inhibits cyclic adenosine monophosphate formation by oligoclonal TSAb, which are highly enriched in GO patients’ sera[1].
TSHR antagonist S37a (10 mg/kg ;i.g.) displays no toxicity and a remarkable 53% oral bioavailability in mice[1].

Reference

[1]. Marcinkowski P, et al. A New Highly Thyrotropin Receptor-Selective Small-Molecule Antagonist with Potential for the Treatment of Graves’ Orbitopathy. Thyroid. 2019 Jan;29(1):111-123.
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