Elesclomol

Elesclomol

Clinical data
ATC code	none
Identifiers
IUPAC name N′1,N′3-dimethyl-N′1,N′3- bis(phenylcarbonothioyl)propanedihydrazide
CAS Number	488832-69-5 Y
PubChem CID	300471
DrugBank	DB05719 Y
ChemSpider	265501 Y
UNII	6UK191M53P
KEGG	D08909
ChEBI	CHEBI:79369 Y
ChEMBL	ChEMBL1972860 Y
E number	{{#property:P628}}
CompTox Dashboard (EPA)	{{#property:P3117}}
ECHA InfoCard	{{#property:P2566}}
Chemical and physical data
Formula	C19H20N4O2S2
Molar mass	400.52 g·mol−1
InChI InChI=1S/C19H20N4O2S2/c1-22(18(26)14-9-5-3-6-10-14)20-16(24)13-17(25)21-23(2)19(27)15-11-7-4-8-12-15/h3-12H,13H2,1-2H3,(H,20,24)(H,21,25) Y Key:BKJIXTWSNXCKJH-UHFFFAOYSA-N Y
NY (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. Synta Pharmaceuticals announced on February 26, 2009 the suspension of all clinical trials involving Elesclomol due to safety concerns. 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.

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).

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.

Studies in preclinical models suggested that Elesclomol may be effective in Ewing sarcoma cells with elevated levels of cellular oxidative stress.

Mechanism of action

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

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.”