Design and synthesis of tag-free photoprobes for the identification of the molecular target for CCG-1423, a novel inhibitor of the Rho/MKL1/SRF signaling pathway

• Jessica L. Bell,
• Andrew J. Haak,
• Susan M. Wade,
• Yihan Sun,
• Richard R. Neubig and
• Scott D. Larsen

Beilstein J. Org. Chem. 2013, 9, 966–973, doi:10.3762/bjoc.9.111

• , University of Michigan, Ann Arbor, MI 48109, USA College of Pharmacy, University of Michigan, Ann Arbor, MI 48109, USA 10.3762/bjoc.9.111 Abstract CCG-1423 and related analogues represent a new class of inhibitors of Rho/MKL1/SRF-mediated gene transcription, a pathway that has been implicated in both cancer

• , click ligation of a fluorescent dye, and gel electrophoresis revealed specific labeling of a single 24 kDa band that could be blocked with an active competitor. Future work will focus on identifying the labeled protein(s). Keywords: CCG-1423; click ligation; photoaffinity labeling; Rho pathway

• that inhibit gene expression mediated by this Rho/MKL1/SRF signaling pathway [8]. The lead CCG-1423 (1, Figure 1) was identified in a cell-based high-throughput screen as an inhibitor of expression of a luciferase reporter gene driven by the serum response element promoter (SRE-Luc) [9]. Analysis of