Literature

Abstract

Conventional and novel protein kinase C (PKC) isozymes are the main targets of tumor promoters. We developed 1-hexylindolactam-V10 ( 5) as a selective activator for novel PKC isozymes that play important roles in various cellular processes related to tumor promotion, ischemia--reperfusion injury in the heart, and Alzheimer's disease. The compound existed as a mixture of three conformers. The trans-amide restricted analogues of 5 ( 14 and 15) hardly bound to PKC isozymes, suggesting that the active conformation of 5 could be that with a cis-amide. Compound 5 selectively translocated novel PKC isozymes over conventional PKC isozymes in HeLa cells at 0.1-1 microM. These results suggest that 5 could be useful for the functional analysis of novel PKC isozymes.

DOI： 10.1021/jm0706719

Synthesis, Conformational Analysis, and Biological Evaluation of 1-Hexylindolactam-V10 as a Selective Activator for Novel Protein Kinase C Isozymes

Journal of Medicinal Chemistry 2008.0

The amide hydrogen of (−)-indolactam-V and benzolactam-V8’s plays a critical role in protein kinase c binding and tumor-promoting activities

Bioorganic & Medicinal Chemistry Letters 2001.0

Synthesis and PKC isozyme surrogate binding of indothiolactam-V, a new thioamide analogue of tumor promoting indolactam-V

Bioorganic & Medicinal Chemistry Letters 2000.0

Modeling, Chemistry, and Biology of the Benzolactam Analogues of Indolactam V (ILV). 2. Identification of the Binding Site of the Benzolactams in the CRD2 Activator-Binding Domain of PKCδ and Discovery of an ILV Analogue of Improved Isozyme Selectivity

Journal of Medicinal Chemistry 1997.0

Novel conformationally constrained analogues of diacylglycerol. Protein kinase C binding affinity of simplified compounds based on a 6-membered lactam moiety

Bioorganic & Medicinal Chemistry Letters 1997.0

Synthesis of the benzofuran analogue of ILV, a new protein kinase C (PKC) activator