TY - JOUR
T1 - (±) cis-bisamido epoxides
T2 - A novel series of potent FXIII-A inhibitors
AU - Avery, Craig A.
AU - Pease, Richard J.
AU - Smith, Kerrie
AU - Boothby, May
AU - Buckley, Helen M.
AU - Grant, Peter J.
AU - Fishwick, Colin W.G.
N1 - Publisher Copyright:
© 2015 Elsevier Masson SAS.
PY - 2015/5/26
Y1 - 2015/5/26
N2 - A novel class of potent FXIII-A inhibitors containing a (±) cis-bisamido epoxide pharmacophore is described. The compounds display highly potent inhibition of FXIII-A (IC50 Combining double low line 5-500 nM) in an in vitro assay. In contrast to other types of previously described covalent transglutaminase inhibitors, the bis-Amido epoxides exhibited no measurable reactivity with glutathione, therefore possibly rendering this class of compounds suitable for future in vivo investigations. Additionally, the compounds show selective inhibition for FXIII-A against the cysteine protease, cathepsin S although they proved to have similar potency with a closely related transglutaminase, TGII, to that observed for FXIII-A.
AB - A novel class of potent FXIII-A inhibitors containing a (±) cis-bisamido epoxide pharmacophore is described. The compounds display highly potent inhibition of FXIII-A (IC50 Combining double low line 5-500 nM) in an in vitro assay. In contrast to other types of previously described covalent transglutaminase inhibitors, the bis-Amido epoxides exhibited no measurable reactivity with glutathione, therefore possibly rendering this class of compounds suitable for future in vivo investigations. Additionally, the compounds show selective inhibition for FXIII-A against the cysteine protease, cathepsin S although they proved to have similar potency with a closely related transglutaminase, TGII, to that observed for FXIII-A.
KW - Bis-Amido epoxides molecular modelling
KW - FXIII-A
KW - Thrombosis
UR - http://www.scopus.com/inward/record.url?scp=84930224852&partnerID=8YFLogxK
U2 - 10.1016/j.ejmech.2015.05.019
DO - 10.1016/j.ejmech.2015.05.019
M3 - Article
C2 - 26005023
AN - SCOPUS:84930224852
SN - 0223-5234
VL - 98
SP - 49
EP - 53
JO - European Journal of Medicinal Chemistry
JF - European Journal of Medicinal Chemistry
ER -