Details
Stereochemistry | ACHIRAL |
Molecular Formula | C19H20N4O2S2 |
Molecular Weight | 400.518 |
Optical Activity | NONE |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
CN(NC(=O)CC(=O)NN(C)C(=S)C1=CC=CC=C1)C(=S)C2=CC=CC=C2
InChI
InChIKey=BKJIXTWSNXCKJH-UHFFFAOYSA-N
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)
DescriptionSources: http://bpsbioscience.com/elesclomol-sta-4783Curator's Comment: Description was created based on several sources, including
https://www.ncbi.nlm.nih.gov/pubmed/18723479
http://adisinsight.springer.com/drugs/800018097
Sources: http://bpsbioscience.com/elesclomol-sta-4783
Curator's Comment: Description was created based on several sources, including
https://www.ncbi.nlm.nih.gov/pubmed/18723479
http://adisinsight.springer.com/drugs/800018097
Elesclomol (also known as STA-4783), originally identified in a cell-based phenotypic screen for pro-apoptotic 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 antitumor activity against a broad spectrum of types of cancer cell in human tumour xenograft models due to its excessive ROS production and elevated levels of oxidative stress leading to the death of cancer cells. Elesclomol is currently being studied as novel cancer therapeutic, in which it has demonstrated the ability to prolong progression-free survival in study subjects. 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. Elesclomol is an HSP-90 Inhibitor with pro-apoptotic and potential antineoplastic activities. Elesclomol induces oxidative stress and triggers mitochondrial-induced apoptosis in cancer cells. Elesclomol 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).
Originator
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL3232688 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18723479 |
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Target ID: CHEMBL614922 Sources: https://www.ncbi.nlm.nih.gov/pubmed/20345134 |
110.0 nM [IC50] | ||
Target ID: CHEMBL383 Sources: https://www.ncbi.nlm.nih.gov/pubmed/20345134 |
9.0 nM [IC50] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
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Primary | Unknown Approved UseUnknown |
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Primary | Unknown Approved UseUnknown |
PubMed
Title | Date | PubMed |
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Drug evaluation: STA-4783--enhancing taxane efficacy by induction of Hsp70. | 2006 Jun |
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Phase I clinical trial of STA-4783 in combination with paclitaxel in patients with refractory solid tumors. | 2007 Jan 15 |
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Elesclomol induces cancer cell apoptosis through oxidative stress. | 2008 Aug |
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Phase II, randomized, controlled, double-blinded trial of weekly elesclomol plus paclitaxel versus paclitaxel alone for stage IV metastatic melanoma. | 2009 Nov 10 |
Patents
Sample Use Guides
In Vivo Use Guide
Sources: https://clinicaltrials.gov/ct2/show/NCT00522834
213 mg/m2 Elesclomol (STA-4783) plus 80 mg/m2 paclitaxel administered intravenously once a week for the first 3 weeks of a 4 week cycle.
Route of Administration:
Intravenous
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/18723479
Elesclomol (100 nM) rapidly induces Hsp70 RNA levels with a 4.8-fold increase at 1 hour and a 160-fold increase at 6 hours in Ramos Burkitt's lymphoma B cells in consistent with the intracellular ROS content which increases by 20% as early as 0.5 hour and 385% at 6 hours
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Classification Tree | Code System | Code | ||
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FDA ORPHAN DRUG |
243607
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NCI_THESAURUS |
C274
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CHEMBL1972860
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ELESCLOMOL
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488832-69-5
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m4866
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6UK191M53P
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100000127739
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DB05719
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DTXSID2042642
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C75291
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RR-128
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300471
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SUB33932
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C512195
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79369
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ACTIVE MOIETY
SALT/SOLVATE (PARENT)