Chiral inversion of the second generation IMiD™ CC-4047 (ACTIMID™) in human plasma and phosphate-buffered saline

• Published in: Chirality (New York, N.Y.) Vol. 15; no. 4; pp. 348 - 351
• Main Authors: Teo, Steve K., Chen, Yong, Muller, George W., Chen, Roger S., D. Thomas, Steve, Stirling, David I., Chandula, Reddy S.
• Format: Journal Article
• Language: English
• Published: New York Wiley Subscription Services, Inc., A Wiley Company 2003
• Subjects: ACTIMID; Adjuvants, Immunologic - blood; Adjuvants, Immunologic - chemistry; Adjuvants, Immunologic - pharmacokinetics; Antineoplastic Agents - blood; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacokinetics; CC-4047; chiral inversion; Humans; IMiD; In Vitro Techniques; isomers; Neoplasms - drug therapy; plasma; racemization; Sodium Chloride; Stereoisomerism; thalidomide; Thalidomide - analogs & derivatives; Thalidomide - blood; Thalidomide - chemistry; Thalidomide - pharmacokinetics
• ISSN: 0899-0042; 1520-636X
• DOI: 10.1002/chir.10221

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‐α, interleukin (IL‐10), and interferon (IFN‐γ). 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. Chirality 15:348–351, 2003. © 2003 Wiley‐Liss, Inc.