NCIt definition : An orally available curaxin-based agent targeting the Facilitates Chromatin Transcription
(FACT) complex, with potential antineoplastic activity. Upon administration, CBL0137
binds to FACT and sequesters the FACT complex on chromatin, which inhibits its activity.
This prevents transcription of certain genes involved in cancer-associated signaling
pathways; it specifically inhibits the transcription of both NF-kappa B and heat shock
transcription factor 1 (HSF1) and simultaneously activates p53. This causes an increase
in tumor cell apoptosis and a decrease in tumor cell proliferation, in FACT-positive
cancers. In addition, this agent is able to sensitize FACT-positive tumor cells to
the cytotoxic effects of other chemotherapeutic agents. FACT, a transcription and
replication factor composed of the Structure Specific Recognition Protein (SSRP1)
and suppressor of Ty 16 (Spt16) proteins, is expressed in a variety of tumor cells
while almost absent in normal cells; its expression is associated with increased tumor
aggressiveness and poor prognosis.;
Semantic type(s)