This immunosuppressive (FW = 390.08 g/mol; CAS 12244-57-4; Symbol:
AuTM), also known as sodium aurothiomalate, gold sodium thiomalate,
Myocrisin?, and sodium 2- (auriosulfanyl) -3-carboxypropanoate, is an
orally active nonsteroidal anti-inflammatory agent for treating rheumatism.
See also Auranofin Even so, the demonstrated effectiveness of low-dose
methotrexate (MTX) has led to a significant decline in using sodium
aurothiomalate. Mode of Action: AuTM markedly inhibits DNA binding
by the transcription factor AP-1, with less potent effects for AP-2, NF-1
and TFIID. In studies of the interactions of the progesterone receptor
(or PR) with its DNA response element (or PRE), AuTM was found to
regulate gene expression, again suggesting that inhibition of binding of a
transcription factor to DNA is a likely mechanism. Electrophoretic
mobility-shift assays showed that AP-1 DNA binding is inhibited by
gold (I) thiolates and selenite, with IC values occurring of 5 μM and 1
50
μM, respectively. Thiomalate was without effect in the absence of gold (I),
and other metal ions inhibited at higher concentrations, in a rank order
correlating with their thiol binding affinities. Cysteine-to-serine mutants
demonstrated that these effects of Au (I) and selenite require Cys272 and
Cys154 in the DNA-binding domains of Jun and Fos, respectively.
Gold (I) thiolates and selenite did not inhibit nonspecific protein binding to
the AP-1 site and were at least an order of magnitude less potent as
inhibitors of sequence-specific binding to the AP-2, TFIID, or NF1 sites
compared with the AP-1 site. Note: Given the chemical reactivity of
AuTM, is is likely that this agent may inhibit other thiol-dependent
processes within cells.
