From Tyrian Purple to Kinase Modulators: Naturally Halogenated Indirubins and Synthetic Analogues

Abstract

Indirubin l " indigo l " Tyrian purple l " Hexaplex trunculus l " Bolinus brandaris l " Muricidae l " protein kinases l " CDKs l " GSK-3β l " stem cells

6BIO Enhances Oligonucleotide Activity in Cells: A Potential Combinatorial Anti-androgen Receptor Therapy in Prostate Cancer Cells

“…These include the CDK family members CDK1, CDK2, and CDK5, in addition to PDK1, JAK/STAT3, and GSK-3a/b. 22,26,40,[43][44][45] GSK-3a/b is a ubiquitously expressed serine-threonine kinase encoded by distinct genes. 47 The two isoforms share 97% sequence homology within their catalytic domains but differ in their C and N termini.…”

“…This is likely due to the inhibition of GSK-3b activity by 6BIO. 40 GSK-3b is known to phosphorylate the b-catenin protein and to enhance its degradation. 41 Blocking the activity of GSK-3b will thus elevate levels of b-catenin.…”

“…Among the reported targets of 6BIO is the GSK-3 kinase, 22,26,40,[43][44][45] which consists of two distinct isoforms, GSK-3a and GSK-3b, and which has been implicated in multiple cellular processes and in prostate cancer pathogenesis. 46,47 To understand the mechanism of action of 6BIO, we used another GSK-3a/b inhibitor, CHIR99021, to determine whether it had similar effects as 6BIO on ASO activity and AR regulation.…”

An evaluation of indirubin analogues as phosphorylase kinase inhibitors

“…Although kinase inhibitors have been discovered from various sources [12][13][14][15], the major obstacle to kinase-directed drugs is the cross-inhibition linked to their highly homologous ATPbinding sites [12]. Staurosporine, although too toxic for clinical use, is a potent inhibitor of PhK (Ki = 0.37 nM) [5].…”

Indirubin 3′-(O-oxiran-2-ylmethyl)oxime: A novel anticancer agent

“…A number of indirubin derivatives have been synthesized and characterized with respect to kinase inhibition and anticancer properties. [5][6][7][8][9][10][11] We reported that 5 0 -methoxyindirubin, but not by indirubin itself, was highly cytotoxic against neuroblastoma cells in comparison with normal cells, human umbilical vein endothelial cells (HUVEC) and normal human dermal fibroblasts (NHDF). 12 More recently, we determined that three of these derivatives, 5-methoxyindirubin, indirubin 3 0 -oxime and 7-methoxyindirubin 3 0 -oxime, suppressed multi-drug resistant gene 1 (MDR1) expression by interaction with a transcription factor, NF-Y, in a tumor cell-type specific manner.…”