Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019204 (hepatocellular carcinoma)
 71,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Helicobacter hepaticus, a causal agent of hepatocarcinoma in mice, exhibits a cytolethal distending toxin activity. The three subunits of this holotoxin, CdtA, CdtB, and CdtC, and three CdtB mutants were produced as recombinant histidine-tagged proteins by using an in vitro cell-free protein expression system. We found that the presence of the three H. hepaticus Cdt subunits is required for cellular toxicity and that only a C-terminal CdtB mutation abolishes the activity of the complex. In vitro, H. hepaticus CdtB exhibits a DNase activity which is also abolished by this C-terminal CdtB mutation. These results suggest that the effect of H. hepaticus CDT probably involves the DNase activity of CdtB.
 ...
PMID:Expression and activity of the cytolethal distending toxin of Helicobacter hepaticus. 1514 1

Cantharidin (CTD), a natural toxin, can inhibit a variety of tumor cell lines, especially hepatocellular carcinoma cells. It is a strong inhibitor of protein phosphatase type 1 (PP1) and type 2A (PP2A). Because of the cytotoxicity, the clinical application of CDT is limited. Here, we review the structure-activity relationships of CDT analogues, including norcantharidin (NCTD), cantharimides and related derivatives of CTDs, which have more powerful antitumor activity but less cytotoxicity than CDT itself. Important advances in the design of the CTD-based inhibitors achieved recently are outlined here in order to establish principles for synthesis, screening, and the applications of promising anti-cancer drug candidates. In addition, efforts to ameliorate the intrinsic cytotoxicity through the use of drug carriers are also discussed. It is conceivable that rational design of the protein phosphatase inhibitors based on cantharidin analogues can be facilitated by studies of mechanism of the protein-inhibitor interactions and the related structural biology in the future.
 ...
PMID:Exploiting protein phosphatase inhibitors based on cantharidin analogues for cancer drug discovery. 2337 56