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Usage

Uses

Used in Pharmaceutical Industry:
Elesclomol is used as an anticancer agent for its potential to target and disrupt cancer cells. It has been shown to modulate various signaling pathways and cellular processes that contribute to cancer progression, making it a promising candidate for cancer treatment.
Used in Drug Delivery Systems:
Elesclomol is also used in the development of novel drug delivery systems to improve its bioavailability, delivery, and therapeutic outcomes. These systems may include organic and metallic nanoparticles as carriers, which can enhance the efficacy of Elesclomol in treating cancer cells.

Biological Activity

elesclomol (also known as sta-4783), originally identified in a cell-based phenotypic screen for proapoptotic activity, is a novel small-molecule that potently induces apoptosis of cancer cells through the rapid generation of reactive oxygen species (ros) and the induction of unmanageable levels of oxidative stress. elesclomol exhibits autitumor activity against a broad spectrum of types of cancer cell in human tumor xengograft models due to its excessive ros production and elevated levels of oxidative stress leading to the death of cancer cells. elesclomol is currently being studies as a novel cancer therapeutic, in which it has demonstrated ability to prolong progression-free survival in study subjects.ronald k. blackman, kahlin cheung-ong, marinella gebbia, david a. proia, suqin he, jane kepros, aurelie jonneaux, philippe marchetti, jerome kluza, patricia e. rao, yumiko wada, guri giaever, corey nislow. mitochondrial electron transport is the cellular target of the oncology drug elesclomol. plos one 2012; 7(1): e29798jessica r. kirshner, suqin he, vishwasenani balasubramanyam, jane kepros, chin-yu yang, mei zhang, zhenjian du, james barsoum, and john bertin. elesclomol induces cancer cell apoptosis through oxidative stress. mol cancer ther 2008; 7:2319-2327

InChI:InChI=1/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)

Upstream product

• 21048-05-5 N-methylbenzothiohydrazide 
• 1663-67-8 malonoyl dichloride 
• 141-82-2 malonic acid 
• 15563-40-3 N-thiobenzoylpiperidine 
• 98-88-4 benzoyl chloride 
• 100-52-7 benzaldehyde 
• 1483-24-5 1-methyl-1-benzoylhydrazine 
• 942-91-6 Carboxymethyl dithiobenzoate 
• 100-58-3 phenylmagnesium bromide 

Downstream Products

• 1224195-72-5 Cu(II)-elesclomol 
• 1224195-73-6 Ni(II)-elesclomol 
• 1183894-81-6 2-(hydroxyimino)-N'1,N'3-dimethyl-N'1,N'3-di(phenylcarbonothioyl)malonohydrazide 
• 1183894-59-8 C₂₂H₂₅N₅O₂S₂ 
• 1080475-35-9 N'1,N'3-bis((E)-(methoxyimino)(phenyl)methyl)-N'1,N'3-dimethylmalonohydrazide 
• 874477-61-9 lithium 2-(N'-methyl-N'-thiobenzoyl-hydrazinocarbonyl)-1-(methyl-thiobenzoyl-hydrazono)-ethanolate 
• 874477-60-8 sodim 2-(N'-methyl-N'-thiobenzoyl-hydrazinocarbonyl)-1-(methyl-thiobenzoyl-hydrazono)-ethanolate 
• 874477-63-1 monopotassium; 2-(N'-methyl-N'-thiobenzoyl-hydrazinocarbonyl)-1-(methyl-thiobenzoyl-hydrazono)-ethanolate 

Relevant academic research and scientific papers

Facile and convenient synthesis of N ′1, N ′3-dialkyl- N ′1, N ′3-bis(arylcarbonothioyl)malonohydrazides via propylphosphonic anhydride coupling

A facile and convenient synthetic method for the anticancer agent elesclomol and its analogues, N′1,N′3-dialkyl-N′1,N′3-bis(arylcarbonothioyl)malonohydrazides, by the direct coupling of N-alkyl-N-(substituted)be

Synthesis, crystallographic characterization and electrochemical property of a copper(II) complex of the anticancer agent elesclomol

Elesclomol is a novel anticancer agent that has been evaluated in a number of late stage clinical trials. A new and convenient synthesis of elesclomol and its copper complex is described. X-ray crystallographic characterization and the electrochemical properties of the elesclomol copper(II) complex are discussed. The copper(II) cation is coordinated in a highly distorted square-planar geometry to each of the sulphur and amide nitrogen atoms of elesclomol. Electrochemical measurements demonstrate that the complex undergoes a reversible one-electron reduction at biologically accessible potentials. In contrast the free elesclomol is found electrochemically inactive. This evidence is in strong support of the mechanism of action we proposed for the anticancer activity of elesclomol.

Syntheses and antitumor activities of N′1, N′3-dialkyl-N′1,N′3-di- (alkylcarbonothioyl) malonohydrazide: The discovery of elesclomol

A series of N′1,N′3-dialkyl- N′1,N′3-di(alkylcarbonothioyl) malonohydrazides have been designed and synthesized as anticancer agents by targeting oxidative stress and Hsp70 induction. Structure-activity relationship (SAR) studies lead to the discovery of STA-4783 (elesclomol), a novel small molecule that has been evaluated in a number of clinical trials as an anticancer agent in combination with Taxol.

Molecular mechanisms of the biological activity of the anticancer drug elesclomol and its complexes with Cu(II), Ni(II) and Pt(II)

The bis(thiohydrazide) amide elesclomol has extremely potent antiproliferative activity and is currently in clinical trials as an anticancer agent. Elesclomol strongly binds copper and may be exerting its cell growth inhibitory effects by generating copper-mediated oxidative stress. Nickel(II) and platinum(II) complexes of elesclomol were synthesized and characterized in order to investigate if these biologically redox inactive metal complexes could also inhibit cell growth. The nickel(II)-elesclomol and platinum(II) elesclomol complexes were 34- and 1040-fold less potent than the copper(II)-elesclomol complex towards human leukemia K562 cells. These results support the conclusion that a redox active metal is required for elesclomol to exert its cell growth inhibitory activity. Copper(II)-elesclomol was also shownto efficiently oxidize ascorbic acid at physiological ascorbic acid concentrations. Reoxidation of the copper(I) thus produced would lead to production of damaging reactive oxygen species. An X-ray crystallographic structure determination of copper(II)-elesclomol showed that it formed a 1:1 neutral complex with a distorted square planar structure. The kinetics and equilibria of the competition reaction of the strong copper(II) chelator TRIEN with copper(II)-elesclomol were studied spectrophotometrically under physiological conditions. These results showed elesclomol bound copper(II) with a conditional stability constant 24-fold larger than TRIEN. A log stability constant of 24.2 was thus indirectly determined for the copper(II)-elesclomol complex.

PROCESS FOR PREPARING BIS(THIOHYDRAZIDE AMIDES)

Disclosed herein are methods of preparing a bis(thio-hydrazide amides) compounds of the following structural formula (I), wherein R1., R3 and Y are defined herein.

Purification of bis (thiohydrazide amides)

Disclosed herein are methods of purifying a bis(thio-hydrazide amides) compounds of the following structural formula: wherein R1, R2, R3, R4, R7, R8, Z, and Y are defined herein.