Elesclomol

Identification

Generic Name
Elesclomol
DrugBank Accession Number
DB05719
Background

Elesclomol is a novel, injectable, drug candidate that kills cancer cells by elevating oxidative stress levels beyond a breaking point, triggering programmed cell death. In preclinical models elesclomol showed potent killing of a broad range of cancer cell types at high doses, and an ability to strongly enhance the efficacy of certain chemotherapy agents, with minimal additional toxicity, at moderate doses. It is being developed by Synta Pharmaceuticals.

Type
Small Molecule
Groups
Investigational
Structure
Weight
Average: 400.518
Monoisotopic: 400.102767284
Chemical Formula
C19H20N4O2S2
Synonyms
  • 1-N'-Benzenecarbothioyl-3-(2-benzenecarbothioyl-2-methylhydrazinyl)-N'-methyl-oxopropanehydrazidide
  • Elesclomol
  • Élesclomol
  • Elesclomolum
External IDs
  • GSK-842879
  • GSK-842879A
  • STA-4783

Pharmacology

Indication

Investigated for use/treatment in melanoma.

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Contraindications & Blackbox Warnings
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Pharmacodynamics

Elesclomol is a first-in-class heat shock protein 70 (Hsp70) inducer that activates natural killer (NK) cell-mediated tumor killing.

Mechanism of action

Elesclomol acts through a novel mechanism of action. Elesclomol has been shown to rapidly cause a dramatic increase in oxidative stress (ROS) inside cancer cells. The prolonged elevation of ROS inside cancer cells induced by elesclomol causes the cell to exceed a critical breaking point and undergo apoptosis. The triggering of the mitochondrial apoptosis pathway is observed within the first six hours of applying elesclomol. Cancer cells operate at a much higher intrinsic level of ROS than normal cells, and have a greatly reduced anti-oxidant capacity compared to normal cells. This leaves them more vulnerable to an agent such as elesclomol that elevates oxidative stress. In similar experiments at similar doses, elesclomol has been found to have little to no impact on normal cells.

Absorption

Not Available

Volume of distribution

Not Available

Protein binding

Not Available

Metabolism
Not Available
Route of elimination

Not Available

Half-life

Not Available

Clearance

Not Available

Adverse Effects
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Toxicity

Not Available

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Not Available
Food Interactions
Not Available

Categories

Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as benzene and substituted derivatives. These are aromatic compounds containing one monocyclic ring system consisting of benzene.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Not Available
Direct Parent
Benzene and substituted derivatives
Alternative Parents
1,3-dicarbonyl compounds / Thioamides / Carboxylic acid hydrazides / Thiocarbonyl compounds / Organopnictogen compounds / Organonitrogen compounds / Organic oxides / Hydrocarbon derivatives
Substituents
1,3-dicarbonyl compound / Aromatic homomonocyclic compound / Carbonyl group / Carboxylic acid derivative / Carboxylic acid hydrazide / Hydrocarbon derivative / Monocyclic benzene moiety / Organic nitrogen compound / Organic oxide / Organic oxygen compound
Molecular Framework
Aromatic homomonocyclic compounds
External Descriptors
carbohydrazide, thiocarbonyl compound (CHEBI:79369)
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
6UK191M53P
CAS number
488832-69-5
InChI Key
BKJIXTWSNXCKJH-UHFFFAOYSA-N
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)
IUPAC Name
N'1,N'3-dibenzenecarbothioyl-N'1,N'3-dimethylpropanedihydrazide
SMILES
CN(NC(=O)CC(=O)NN(C)C(=S)C1=CC=CC=C1)C(=S)C1=CC=CC=C1

References

General References
  1. Gehrmann M: Drug evaluation: STA-4783--enhancing taxane efficacy by induction of Hsp70. Curr Opin Investig Drugs. 2006 Jun;7(6):574-80. [Article]
  2. Berkenblit A, Eder JP Jr, Ryan DP, Seiden MV, Tatsuta N, Sherman ML, Dahl TA, Dezube BJ, Supko JG: Phase I clinical trial of STA-4783 in combination with paclitaxel in patients with refractory solid tumors. Clin Cancer Res. 2007 Jan 15;13(2 Pt 1):584-90. [Article]
KEGG Drug
D08909
PubChem Compound
300471
PubChem Substance
175427028
ChemSpider
265501
ChEBI
79369
ChEMBL
CHEMBL1972860
ZINC
ZINC000001716098
Wikipedia
Elesclomol

Clinical Trials

Clinical Trials

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.00282 mg/mLALOGPS
logP2.34ALOGPS
logP2.81Chemaxon
logS-5.2ALOGPS
pKa (Strongest Acidic)10.9Chemaxon
pKa (Strongest Basic)-8.4Chemaxon
Physiological Charge0Chemaxon
Hydrogen Acceptor Count2Chemaxon
Hydrogen Donor Count2Chemaxon
Polar Surface Area64.68 Å2Chemaxon
Rotatable Bond Count6Chemaxon
Refractivity115.48 m3·mol-1Chemaxon
Polarizability41.29 Å3Chemaxon
Number of Rings2Chemaxon
Bioavailability1Chemaxon
Rule of FiveYesChemaxon
Ghose FilterYesChemaxon
Veber's RuleNoChemaxon
MDDR-like RuleNoChemaxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+0.7792
Blood Brain Barrier+0.9556
Caco-2 permeable-0.5273
P-glycoprotein substrateNon-substrate0.8186
P-glycoprotein inhibitor INon-inhibitor0.6672
P-glycoprotein inhibitor IINon-inhibitor0.9597
Renal organic cation transporterNon-inhibitor0.9014
CYP450 2C9 substrateNon-substrate0.6508
CYP450 2D6 substrateNon-substrate0.8242
CYP450 3A4 substrateNon-substrate0.5524
CYP450 1A2 substrateNon-inhibitor0.6271
CYP450 2C9 inhibitorNon-inhibitor0.601
CYP450 2D6 inhibitorNon-inhibitor0.9158
CYP450 2C19 inhibitorNon-inhibitor0.6511
CYP450 3A4 inhibitorNon-inhibitor0.5964
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.6067
Ames testNon AMES toxic0.6926
CarcinogenicityNon-carcinogens0.5242
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.3817 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9753
hERG inhibition (predictor II)Non-inhibitor0.7308
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSsplash10-00di-0921000000-b8ea4f073a5ad5d4a8fa
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-0uk9-0600900000-b6d9f138711aff72ffbd
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-0002-0129000000-1d159b01e434729a20e1
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-00di-0900000000-d320593c586af479e3ab
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-06fu-4921000000-7326e56933ce44927643
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-00di-1900000000-87b889a497525bc768bf
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-00di-5900000000-42babc08e2b77b90ef72
Predicted 1H NMR Spectrum1D NMRNot Applicable
Predicted 13C NMR Spectrum1D NMRNot Applicable
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-205.5750798
predicted
DarkChem Lite v0.1.0
[M-H]-181.94038
predicted
DeepCCS 1.0 (2019)
[M+H]+205.9044798
predicted
DarkChem Lite v0.1.0
[M+H]+184.29839
predicted
DeepCCS 1.0 (2019)
[M+Na]+205.2880798
predicted
DarkChem Lite v0.1.0
[M+Na]+191.31746
predicted
DeepCCS 1.0 (2019)

Drug created at November 18, 2007 18:27 / Updated at January 14, 2023 19:03