Elesclomol

Elesclomol
Skeletal formula
Space-filling model
Systematic (IUPAC) name
N′1,N′3-dimethyl-N′1,N′3- bis(phenylcarbonothioyl)propanedihydrazide
Identifiers
CAS Number 488832-69-5 YesY
ATC code None
PubChem CID 300471
ChemSpider 265501 YesY
UNII 6UK191M53P YesY
ChEBI CHEBI:79369 N
ChEMBL CHEMBL1972860 N
Chemical data
Formula C19H20N4O2S2
Molar mass 400.518 g/mol
 NYesY (what is this?)  (verify)

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 metastatic melanoma.[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]

In a small, randomized phase II study, elesclomol was shown to significantly increase progression-free survival in people with metastatic melanoma when given in addition to paclitaxel (Taxol).[4][5]

Mechanism of action

Elesclomol induces oxidative stress by provoking a buildup of reactive oxygen species within cancer cells.[6] 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.[7]

Discovery

Elesclomol was first synthesized at Taras Shevchenko National University in Kiev, Ukraine. It's efficiency against cancer was discovered by taiwaneese cell biologist Lan Bo Chen who purchased a batch of eleschomol, among tens of thousands of other compounds, for the purpose of mass drug screening. “It was pure chemist’s joy,” Chen later said. “Homemade, random, and clearly made for no particular purpose. It was the only one that worked on everything we tried.”[8]

References

  1. ↑ "Synta And GlaxoSmithKline Announce Elesclomol Granted Orphan Drug Designation By The FDA" (Press release). Medical News Today. January 30, 2008. Retrieved November 30, 2008.
  2. ↑ "Synta Pharmaceuticals press release". February 26, 2009.
  3. ↑ "Synta Announces Elesclomol Clinical Development to Resume". March 2, 2010.
  4. ↑ "Prous Science Molecule of the Month: Elesclomol". Thomson Reuters. December 2007. Retrieved November 30, 2008.
  5. ↑ Qu Y, Wang J, Sim MS; et al. (June 2010). "Elesclomol, counteracted by Akt survival signaling, enhances the apoptotic effect of chemotherapy drugs in breast cancer cells". Breast Cancer Res. Treat. 121 (2): 311–21. doi:10.1007/s10549-009-0470-6. PMID 19609669.
  6. ↑ Kirshner JR, He S, Balasubramanyam V; et al. (August 2008). "Elesclomol induces cancer cell apoptosis through oxidative stress". Mol Cancer Ther 7 (8): 2319–27. doi:10.1158/1535-7163.MCT-08-0298. PMID 18723479.
  7. ↑ Yadav AA, Patel D, Hasinoff BB (Sep 2013). "Molecular mechanisms of the biological activity of the anticancer drug elesclomol and its complexes with Cu(II), Ni(II) and Pt(II)". J Inorg Biochem 126: 1–6. doi:10.1016/j.jinorgbio.2013.04.013. PMID 23707906.
  8. ↑ "The Treatment - Why is it so difficult to develop drugs for cancer?". The New Yorker. May 17, 2010. Retrieved September 13, 2014.


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