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WAY-204688

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WAY-204688
Clinical data
Drug classNonsteroidal estrogen; Nuclear factor κB inhibitor
Identifiers
  • (2S)-2-[(S)-(2-methoxyphenyl)naphthalen-1-ylmethyl]-2-methyl-3-oxo-3-[4-[3-(trifluoromethyl)phenyl]piperidin-1-yl]propanenitrile
CAS Number
PubChem CID
ChemSpider
UNII
ChEMBL
Chemical and physical data
FormulaC34H31F3N2O2
Molar mass556.629 g·mol−1
3D model (JSmol)
  • C[C@@](C#N)([C@H](C1=CC=CC=C1OC)C2=CC=CC3=CC=CC=C32)C(=O)N4CCC(CC4)C5=CC(=CC=C5)C(F)(F)F
  • 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
  • Key:JZPONCMNBSEYQW-CQTOTRCISA-N

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 IC50Tooltip half-maximal inhibitory concentration of 122 nM and with maximal inhibition relative to estradiol of 94%.[3][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.[3][4] 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.[3][4] It reached phase I clinical trials prior to the discontinuation of its development.[1]

References

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  1. ^ a b "SIM 688 - AdisInsight".
  2. ^ Ivanenkov YA, Balakin KV, Lavrovsky Y (January 2011). "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. doi:10.2174/138955711793564079. PMID 21034406.
  3. ^ a b c d Dodge JA, Richardson TI (2007). "Chapter 10 Novel Selective Estrogen Receptor Modulators (SERMs)". Annual Reports in Medicinal Chemistry Volume 42. Vol. 42. pp. 147–160. doi:10.1016/S0065-7743(07)42010-3. ISBN 978-0-12-373912-4. ISSN 0065-7743.
  4. ^ a b c Opal SM, Palardy JE, Cristofaro P, Parejo N, Jhung JW, Keith JC, et al. (December 2005). "The activity of pathway-selective estrogen receptor ligands in experimental septic shock". Shock. 24 (6): 535–540. doi:10.1097/01.shk.0000183388.90895.cb. PMID 16317384. S2CID 12169698.
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