Protein kinase C (PKC) isozymes are widely recognized as targets for anticancer therapy, and recent investigations demonstrated that PKC activators are potential therapeutic candidates for Alzheimer's disease and acquired immune deficiency syndrome. However, concerns exist about their therapeutic uses because most PKC activators are potent tumor promoters. Bryostatin 1 (bryo-1) is a unique PKC activator with little tumor-promoting activities. Bryo-1 is currently undergoing clinical trials for the treatment of cancer. However, its limited availability from natural sources and difficulty in the synthesis hamper further studies on its mode of action and structural optimization. Although excellent practical methods for synthesizing several bryo-1-related compounds have been developed, the identification of synthetically more accessible compounds with bryo-1-like activity also provides a promising way to circumvent the problem of supply. The authors focused on the bryo-1's unique mechanism of activating PKCδ that plays a tumor suppressor role, and found that a simple and less lipophilic analogue (aplog-1) of the tumor-promoting aplysiatoxin showed PKCδ-activating behavior similar to bryo-1. Aplog-1 was easily synthesized in only 22 ...Continue Reading
Molecular cloning of the cDNA encoding a receptor tyrosine kinase-related molecule with a catalytic region homologous to c-met.
Non-promoting 12-deoxyphorbol 13-esters as potent inhibitors of phorbol 12-myristate 13-acetate-induced acute and chronic biological responses in CD-1 mouse skin
A nonpromoting phorbol from the samoan medicinal plant Homalanthus nutans inhibits cell killing by HIV-1
The large-scale isolation of bryostatin 1 from Bugula neritina following current good manufacturing practices
The metabolism of indole alkaloid tumor promoter, (-)-indolactam V, which has the fundamental structure of teleocidins, by rat liver microsomes
Bryostatin 1, an activator of protein kinase C, inhibits tumor promotion by phorbol esters in SENCAR mouse skin
Aplysiatoxin and debromoaplysiatoxin, constituents of the marine mollusk Stylocheilus longicauda (Quoy and Gaimard, 1824)
Bromine residue at hydrophilic region influences biological activity of aplysiatoxin, a tumor promoter
Crystal structure of the cys2 activator-binding domain of protein kinase C delta in complex with phorbol ester
Identification, activity, and structural studies of peptides incorporating the phorbol ester-binding domain of protein kinase C
Visualization of A beta 42(43) and A beta 40 in senile plaques with end-specific A beta monoclonals: evidence that an initially deposited species is A beta 42(43)
Non-equivalent roles for the first and second zinc fingers of protein kinase Cdelta. Effect of their mutation on phorbol ester-induced translocation in NIH 3T3 cells.
Aplysiatoxin and debromoaplysiatoxin as the causative agents of a red alga Gracilaria coronopifolia poisoning in Hawaii
Cysteine-rich regions of protein kinase Cdelta are functionally non-equivalent. Differences between cysteine-rich regions of non-calcium-dependent protein kinase Cdelta and calcium-dependent protein kinase Cgamma
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 PKCdelta and discovery of an ILV analogue of improved isozyme selectivity
Clarification of the binding mode of teleocidin and benzolactams to the Cys2 domain of protein kinase Cdelta by synthesis of hydrophobically modified, teleocidin-mimicking benzolactams and computational docking simulation
Differential localization of protein kinase C delta by phorbol esters and related compounds using a fusion protein with green fluorescent protein
The lipophilicity of phorbol esters as a critical factor in determining the pattern of translocation of protein kinase C delta fused to green fluorescent protein
Synthesis and PKC isozyme surrogate binding of indothiolactam-V, a new thioamide analogue of tumor promoting indolactam-V
Phase II trial of the use of paclitaxel and gemcitabine as a salvage treatment in metastatic breast cancer
Toward the identification of selective modulators of protein kinase C (PKC) isozymes: establishment of a binding assay for PKC isozymes using synthetic C1 peptide receptors and identification of the critical residues involved in the phorbol ester binding
Evidence for the biosynthesis of bryostatins by the bacterial symbiont "Candidatus Endobugula sertula" of the bryozoan Bugula neritina.
Prostratin: activation of latent HIV-1 expression suggests a potential inductive adjuvant therapy for HAART.
Protein kinase C: structural and spatial regulation by phosphorylation, cofactors, and macromolecular interactions
Binding selectivity of conformationally restricted analogues of (-)-indolactam-V to the C1 domains of protein kinase C isozymes
Indolactam and benzolactam compounds as new medicinal leads with binding selectivity for C1 domains of protein kinase C isozymes
bryA: an unusual modular polyketide synthase gene from the uncultivated bacterial symbiont of the marine bryozoan Bugula neritina
An in-depth comparison of latent HIV-1 reactivation in multiple cell model systems and resting CD4+ T cells from aviremic patients
Anti-Chikungunya viral activities of aplysiatoxin-related compounds from the marine cyanobacterium Trichodesmium erythraeum
Three-dimensional lung tumor microenvironment modulates therapeutic compound responsiveness in vitro--implication for drug development
Synthesis and biological activities of simplified analogs of the natural PKC ligands, bryostatin-1 and aplysiatoxin
Review of bioactive secondary metabolites from marine bryozoans in the progress of new drugs discovery
Heat shock proteins regulate activation-induced proteasomal degradation of the mature phosphorylated form of protein kinase C.
Sunitinib impedes brain tumor progression and reduces tumor-induced neurodegeneration in the microenvironment
Fluorescence resonance energy transfer-based screening for protein kinase C ligands using 6-methoxynaphthalene-labeled 1,2-diacylglycerol-lactones.
Structure-activity studies on the spiroketal moiety of a simplified analogue of debromoaplysiatoxin with antiproliferative activity
Two Marine Cyanobacterial Aplysiatoxin Polyketides, Neo-debromoaplysiatoxin A and B, with K+ Channel Inhibition Activity
Birth defects encompass structural and functional alterations that occur during embryonic or fetal development and are present since birth. The cause may be genetic, environmental or unknown and can result in physical and/or mental impairment. Here is the latest research on birth defects.