Elesclomol (
INN, codenamed STA-4783) is a drug that triggers
apoptosis (programmed cell death) in
cancer cells. It is being developed by
Synta Pharmaceuticals and
GlaxoSmithKline as a
chemotherapy adjuvant, and has received both
fast track and
orphan drug status from the
U.S. Food and Drug Administration for the treatment of
metastaticmelanoma.[1] Synta Pharmaceuticals announced on February 26, 2009 the suspension of all clinical trials involving Elesclomol due to safety concerns.[2] In March 2010, Synta announced that the FDA had approved resuming clinical development of elesclomol, and that they expected to initiate one or more clinical trials for elesclomol in the second half of the year.[3]
Results from a phase III trial were announced in March 2013. The study was halted when it was determined that addition of elesclomol to paclitaxel didn't significantly increase progression-free survival.[6]
Studies in preclinical models suggested that Elesclomol may be effective in Ewing sarcoma cells with elevated levels of cellular oxidative stress.[7]
Mechanism of action
Elesclomol induces
oxidative stress by provoking a buildup of
reactive oxygen species within cancer cells.[8] Elesclomol requires a redox active metal ion to function. The Cu(II) complex is 34 times more potent than the Ni(II) complex and 1040-fold more potent than the Pt(II) complex.[9]
Discovery
Elesclomol was first synthesized at Shinogi BioResearch in Lexington, MA. Its efficacy against cancer was discovered by scientists at Shionogi BioResearch. “It was pure chemist’s joy,” Synta's Chen said. “Homemade, random, and clearly made for no particular purpose. It was the only one that worked on everything we tried.”[10]
^Qu Y, Wang J, Sim MS, Liu B, Giuliano A, Barsoum J, Cui X (June 2010). "Elesclomol, counteracted by Akt survival signaling, enhances the apoptotic effect of chemotherapy drugs in breast cancer cells". Breast Cancer Research and Treatment. 121 (2): 311–21.
doi:
10.1007/s10549-009-0470-6.
PMID19609669.
S2CID1312270.
^Yadav AA, Patel D, Wu X, Hasinoff BB (September 2013). "Molecular mechanisms of the biological activity of the anticancer drug elesclomol and its complexes with Cu(II), Ni(II) and Pt(II)". Journal of Inorganic Biochemistry. 126: 1–6.
doi:
10.1016/j.jinorgbio.2013.04.013.
PMID23707906.
S2CID20624982.