Stability constants of metal complexes of bithionol, fenticlor and hexachlorophene

Fogg, Arnold G.; Gray, Andrew; Burns, D. Thorburn

doi:10.1016/s0003-2670(01)95715-0

Cited by 4 publications

(3 citation statements)

References 8 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Based on our binding affinities for Mg 2+ and Ca 2+ as well as published metal affinities for hexachlorophene and bithionol, inhibitors that chelate metal ions (discussed below; ref. 42), enough metal ions remained in the assay buffer for full ATX activity. Thus, metal chelation is not the cause of the observed inhibition.…”

mentioning

confidence: 99%

Identification of small-molecule inhibitors of autotaxin that inhibit melanoma cell migration and invasion

Saunders

Ouellette

Bandle

et al. 2008

Molecular Cancer Therapeutics

View full text Add to dashboard Cite

Autotaxin (ATX) is a prometastatic enzyme initially isolated from the conditioned medium of human melanoma cells that stimulates a myriad of biological activities, including angiogenesis and the promotion of cell growth, survival, and differentiation through the production of lysophosphatidic acid (LPA). ATX increases the aggressiveness and invasiveness of transformed cells, and ATX levels directly correlate with tumor stage and grade in several human malignancies. To study the role of ATX in the pathogenesis of malignant melanoma, we developed antibodies and small-molecule inhibitors against recombinant human protein. Immunohistochemistry of paraffinembedded human tissue shows that ATX levels are markedly increased in human primary and metastatic melanoma relative to benign nevi. Chemical screens identified several small-molecule inhibitors with binding constants ranging from nanomolar to low micromolar. Cell migration and invasion assays with melanoma cell lines show that ATX markedly stimulates melanoma cell migration and invasion, an effect suppressed by ATX inhibitors. The migratory phenotype can be rescued by the addition of the enzymatic product of ATX, LPA, confirming that the observed inhibition is linked to suppression of LPA production by ATX. Chemical analogues of the inhibitors show structure-activity relationships important for ATX inhibition and indicate pathways for their optimization. These studies suggest that ATX is an approachable molecular target for the rational design of chemotherapeutic agents directed against malignant melanoma. [Mol Cancer Ther 2008;7(10):3352 -62]

show abstract

mentioning

confidence: 99%

Identification of small-molecule inhibitors of autotaxin that inhibit melanoma cell migration and invasion

Saunders

Ouellette

Bandle

et al. 2008

Molecular Cancer Therapeutics

View full text Add to dashboard Cite

show abstract

“…Another ATX inhibitor is bithionol ( 24 , Table ), , a known metal ion chelating molecule like l -histidine and EDTA . The latter two inhibit ATX by scavenging metal ions in solution, which are required for ATX activity.…”

Section: Small Molecule Inhibitors Of Atxmentioning

confidence: 99%

“…77 Another ATX inhibitor is bithionol (24, Table 3), 73,74 a known metal ion chelating molecule like L-histidine and EDTA. 78 The latter two inhibit ATX by scavenging metal ions in solution, which are required for ATX activity. However, inhibitor 24 appears to act directly on ATX and not via metal chelation, since the K i value of 24 for ATX is 2 orders of magnitude lower than the used metal ion concentration.…”

Section: Small Molecule Inhibitors Of Atxmentioning

confidence: 99%