WAY-204688

Names

[ CAS No. ]:
796854-35-8

[ Name ]:
WAY-204688

[Synonym ]:
1-Piperidinepropanenitrile, α-[(S)-(2-methoxyphenyl)-1-naphthalenylmethyl]-α-methyl-β-oxo-4-[3-(trifluoromethyl)phenyl]-, (αS)-
(2S,3S)-3-(2-Methoxyphenyl)-2-methyl-3-(1-naphthyl)-2-({4-[3-(trifluoromethyl)phenyl]-1-piperidinyl}carbonyl)propanenitrile
(2S,3S)-3-(2-methoxyphenyl)-2-methyl-3-(naphthalen-1-yl)-2-({4-[3-(trifluoromethyl)phenyl]piperidin-1-yl}carbonyl)propanenitrile

Biological Activity

[Description]:

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.

[Related Catalog]:

Research Areas >> Inflammation/Immunology

[Target]

NF-κB-luc:122 nM (IC50, in HAECT-1 cell)

NF-κB


[In Vitro]

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].

[In Vivo]

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].

[References]

[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.


[Related Small Molecules]

BAY 11-7082 | Ammonium 1-pyrrolidinedithiocarbamate | SN50 | Triptolide | JSH-23 | Shikonine | Bay 11-7085 | Rocaglamide | (-)-DHMEQ | Dihydroartemisinin | Tomatidine | QNZ (EVP4593) | Baicalin | Laquinimod | Parthenolide

Chemical & Physical Properties

[ Density]:
1.2±0.1 g/cm3

[ Boiling Point ]:
708.7±60.0 °C at 760 mmHg

[ Molecular Formula ]:
C34H31F3N2O2

[ Molecular Weight ]:
556.617

[ Flash Point ]:
382.4±32.9 °C

[ Exact Mass ]:
556.233765

[ LogP ]:
7.99

[ Vapour Pressure ]:
0.0±2.3 mmHg at 25°C

[ Index of Refraction ]:
1.589

[ Storage condition ]:
2-8℃

Related Compounds