LSZ-102

• CAT Number: I020259
• CAS Number: 2135600-76-7
• Molecular Formula: C25H17F3O4S
• Molecular Weight: 470.46
• Purity: ≥95%
• Synonyms: (E)-3-[4-[[2-[2-(1,1-difluoroethyl)-4-fluorophenyl]-6-hydroxy-1-benzothiophen-3-yl]oxy]phenyl]prop-2-enoic acid
• InChI: InChI=1S/C25H17F3O4S/c1-25(27,28)20-12-15(26)5-9-18(20)24-23(19-10-6-16(29)13-21(19)33-24)32-17-7-2-14(3-8-17)4-11-22(30)31/h2-13,29H,1H3,(H,30,31)/b11-4+
• InChIKey: SJXNPGGVGZXKKI-NYYWCZLTSA-N
• SMILES: CC(C1=C(C=CC(=C1)F)C2=C(C3=C(S2)C=C(C=C3)O)OC4=CC=C(C=C4)C=CC(=O)O)(F)F

LSZ-102 is a potent, orally bioavailable selective estrogen receptor degrader with an IC50 of 0.2 nM.
LSZ-102 is a potent, orally bioavailable selective estrogen receptor degrader with an IC50 of 0.2 nM and currently in Phase I/Ib trials for the treatment of ERα positive breast cancer. LSZ-102 induces significant degradation of ERα after 24 h, when given as a 10 μM solution to MCF-7 cells. Robust inhibition of cell proliferation in MCF-7 cells is observed upon incubation with LSZ-102 with a half inhibitory concentration of 1.7 nM. Results demonstrate that LSZ-102 effectively inhibits the estrogen-induced activation of the ERE-luciferase reporter using charcoal-stripped serum treated with E2 with IC50 of 0.3 nM[1].
Treatment of the mice with LSZ-102 once daily at 20 mg/kg results in significant tumor growth inhibition as compare to the control group treated with vehicle alone, resulting in tumor stasis (mean change in tumor volume of LSZ-102 vs control=%ΔT/ΔC of 2.4% on day 48, p<0.05). Dosing of 3 mg/kg solution of LSZ-102 in male Sprague-Dawley rats results in 33% bioavailability and a dose-normalized exposure of 620 nM•h[1].

Reference

[1]. Tria GS, et al. Discovery of LSZ102, a Potent, Orally Bioavailable Selective Estrogen Receptor Degrader (SERD) for the Treatment of Estrogen Receptor Positive Breast Cancer. J Med Chem. 2018 Apr 12;61(7):2837-2864.
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