WAY-204688

• CAT Number: I013513
• CAS Number: 796854-35-8
• Molecular Formula: C34H31F3N2O2
• Molecular Weight: 556.62
• Purity: ≥95%
• Synonyms: (2S)-2-[(S)-(2-methoxyphenyl)-naphthalen-1-ylmethyl]-2-methyl-3-oxo-3-[4-[3-(trifluoromethyl)phenyl]piperidin-1-yl]propanenitrile
• InChI: InChI=1S/C34H31F3N2O2/c1-33(22-38,32(40)39-19-17-23(18-20-39)25-11-7-12-26(21-25)34(35,36)37)31(29-14-5-6-16-30(29)41-2)28-15-8-10-24-9-3-4-13-27(24)28/h3-16,21,23,31H,17-20H2,1-2H3/t31-,33+/m0/s1
• InChIKey: JZPONCMNBSEYQW-CQTOTRCISA-N
• SMILES: CC(C#N)(C(C1=CC=CC=C1OC)C2=CC=CC3=CC=CC=C32)C(=O)N4CCC(CC4)C5=CC(=CC=C5)C(F)(F)F

WAY-204688 is an estrogen receptor (ER-α) selective, orally active inhibitor of NF-κB transcriptional activity with an IC50 of 122 ± 30 nM for NF-κB-luciferase (NF-κB-luc) in HAECT-1 cells.
WAY-204688 is ER-dependenrt (activity seen only when hER is coexpressed with NF-κB-luciferase in human aortic endothelial cell lines (HAECT-1) cells). The interaction of WAY-204688 with ERα and ERβ is examined in vitro. WAY-204688 displaces [3H]E2 from the ERα ligand binding domain protein (LBD) with IC50=2.43 μM and from the ERβ ligand binding domain protein (LBD) with IC50=1.5 μM[1].
WAY-204688 (5 mg/kg per day, po daily for 5 weeks) is evaluated in vivo for the ability to inhibit four proinflammatory genes (MHC, invariant chain (MHI), VCAM-1, RANTES, and TNF-α). The effect of WAY-204688 on induction of the gene products and on uterine wet weight is compared to that of 17α-ethinyl 17β-estradiol (EE at 10 μg/kg per day) in the same paradigm. Further characterization of WAY-204688 is carried out in several preclinical models of inflammatory disease. In the Lewis rat adjuvant-induced arthritis model (AIA), WAY-204688 is active at a dose of 0.3 mg/kg per day, po[1].

Reference

[1]. Caggiano TJ, et al. Estrogen receptor dependent inhibitors of NF-kappaB transcriptional activation-1 synthesis and biological evaluation of substituted 2-cyanopropanoic acid derivatives: pathway selective inhibitors of NF-kappaB, a potential treatment for rheumatoid arthritis. J Med Chem. 2007 Nov 1;50(22):5245-8.
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