WAY-204688 explained

WAY-204688, also known as SIM-688, is a synthetic nonsteroidal estrogen and nuclear factor κB (NF-κB) inhibitor which was originated by ArQule and Wyeth and was under development by Wyeth for the treatment of rheumatoid arthritis, non-specific inflammation, and sepsis but was never marketed.^{[1] [2] [3]} It is a "pathway-selective" estrogen receptor (ER) ligand which inhibits NF-κB with an of 122 nM and with maximal inhibition relative to estradiol of 94%.^[4] Inhibition of NF-κB by WAY-204688 appears to be dependent on agonism of the ERα, as it is reversed by the ERα antagonist fulvestrant, but is not dependent on the ERβ. In contrast to the case of NF-κB inhibition, WAY-204688 produces only slight elevation of creatine kinase in vitro, a measure of classical estradiol effects. It reached phase I clinical trials prior to the discontinuation of its development.

External links

• SIM-688 (WAY-204688) - AdisInsight

Notes and References

1. Web site: SIM 688 - AdisInsight.
2. Ivanenkov YA, Balakin KV, Lavrovsky Y . Small molecule inhibitors of NF-kB and JAK/STAT signal transduction pathways as promising anti-inflammatory therapeutics . Mini Reviews in Medicinal Chemistry . 11 . 1 . 55–78 . January 2011 . 21034406 . 10.2174/138955711793564079 .
3. Book: Dodge JA, Richardson TI . Annual Reports in Medicinal Chemistry Volume 42. Chapter 10 Novel Selective Estrogen Receptor Modulators (SERMs). 42. 2007. 147–160. 0065-7743. 10.1016/S0065-7743(07)42010-3. 978-0-12-373912-4.
4. Opal SM, Palardy JE, Cristofaro P, Parejo N, Jhung JW, Keith JC, Chippari S, Caggiano TJ, Steffan RJ, Chadwick CC, Harnish DC . The activity of pathway-selective estrogen receptor ligands in experimental septic shock . Shock . 24 . 6 . 535–540 . December 2005 . 16317384 . 10.1097/01.shk.0000183388.90895.cb . 12169698 . free .