Chiral inversion of the second generation IMiD CC-4047 (ACTIMID ) in human plasma and phosphate-buffered saline.
CC-4047 is a racemic second-generation immunomodulatory drug currently in clinical development for various oncologic indications. It has potent effects on key cytokines including tumor necrosis factor-alpha, interleukin (IL-10), and interferon (IFN-gamma). The S-isomer of CC-4047 has been reported to be the more potent enantiomer of the racemate. In this article we report on the rapid racemization of the S-isomer of CC-4047 in human plasma and phosphate-buffered saline. These results support the further development of the racemate instead of the S-isomer.
Teo
Steve K
SK
Celgene Corp., Warren, New Jersey 07059, USA. steo@celgene.com
Chen
Yong
Y
Muller
George W
GW
Chen
Roger S
RS
Thomas
Steve D
SD
Stirling
David I
DI
Chandula
Reddy S
RS
D000276:Adjuvants, Immunologic / Q000097:blood* / Q000737:chemistry* / Q000493:pharmacokinetics; D000970:Antineoplastic Agents / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D006801:Humans; D066298:In Vitro Techniques; D009369:Neoplasms / Q000188:drug therapy; D012965:Sodium Chloride; D013237:Stereoisomerism; D013792:Thalidomide / Q000031:analogs & derivatives / Q000097:blood* / Q000737:chemistry* / Q000493:pharmacokinetics
D000276:Adjuvants, Immunologic; D000970:Antineoplastic Agents; D012965:Sodium Chloride; D013792:Thalidomide; C467566:pomalidomide