NAV

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
 3D
Similar Structures
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行为通过小说的行动机制n. 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/ADRsBrowse all" title="" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
Not Available

Interactions

Drug InteractionsLearn More" title="" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
这些信息不应该被解释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 byClassyfire
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 TrialsLearn More" title="" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count
3 Terminated Treatment Melanoma 1
2 Completed Treatment Brenner Tumor/Clear Cell Adenocarcinoma of the Fallopian Tubes/Endometrioid Adenocarcinoma of the Fallopian Tubes/Fallopian Tube Serous Adenocarcinoma/Fallopian Tube Transitional Cell Carcinoma/Mucinous Adenocarcinoma of the Fallopian Tubes/Ovarian Clear Cell Adenocarcinoma/Ovarian Endometrioid Adenocarcinoma/卵巢粘液腺癌/Ovarian Seromucinous Carcinoma/Ovarian Transitional Cell Tumor/Primary Peritoneal Serous Adenocarcinoma/Recurrent Fallopian Tube Carcinoma/Recurrent Ovarian Carcinoma/Recurrent Primary Peritoneal Carcinoma/Serous Adenocarcinoma of Ovary/Undifferentiated Fallopian Tube Carcinoma/Undifferentiated Ovarian Carcinoma 1
2 Completed Treatment Soft Tissue Sarcoma 1
1 Completed Treatment Neoplasm 1
1, 2 Completed Treatment Melanoma 1
1, 2 Completed Treatment Stage IIIB Non-Small Cell Lung Cancer/Stage IV Non-small Cell Lung Cancer (NSCLC) 1

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
Property Value Source
Water Solubility 0.00282 mg/mL ALOGPS
logP 2.34 ALOGPS
logP 2.81 Chemaxon
logS -5.2 ALOGPS
pKa (Strongest Acidic) 10.9 Chemaxon
pKa (Strongest Basic) -8.4 Chemaxon
Physiological Charge 0 Chemaxon
Hydrogen Acceptor Count 2 Chemaxon
Hydrogen Donor Count 2 Chemaxon
Polar Surface Area 64.68 Å2 Chemaxon
Rotatable Bond Count 6 Chemaxon
Refractivity 115.48 m3·mol-1 Chemaxon
Polarizability 41.29 Å3 Chemaxon
Number of Rings 2 Chemaxon
Bioavailability 1 Chemaxon
Rule of Five Yes Chemaxon
Ghose Filter Yes Chemaxon
Veber's Rule No Chemaxon
MDDR-like Rule No Chemaxon
Predicted ADMET Features
Property Value Probability
Human Intestinal Absorption + 0.7792
Blood Brain Barrier + 0.9556
Caco-2 permeable - 0.5273
P-glycoprotein substrate Non-substrate 0.8186
P-glycoprotein inhibitor I Non-inhibitor 0.6672
P-glycoprotein inhibitor II Non-inhibitor 0.9597
Renal organic cation transporter Non-inhibitor 0.9014
CYP450 2C9 substrate Non-substrate 0.6508
CYP450 2D6 substrate Non-substrate 0.8242
CYP450 3A4 substrate Non-substrate 0.5524
CYP450 1A2 substrate Non-inhibitor 0.6271
CYP450 2C9 inhibitor Non-inhibitor 0.601
CYP450 2D6 inhibitor Non-inhibitor 0.9158
CYP450 2C19 inhibitor Non-inhibitor 0.6511
CYP450 3A4 inhibitor Non-inhibitor 0.5964
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.6067
Ames test Non AMES toxic 0.6926
Carcinogenicity Non-carcinogens 0.5242
Biodegradation Not ready biodegradable 1.0
Rat acute toxicity 2.3817 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.9753
hERG inhibition (predictor II) Non-inhibitor 0.7308
ADMET data is predicted usingadmetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
Spectrum Spectrum Type Splash Key
Predicted GC-MS Spectrum - GC-MS Predicted GC-MS Not Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS Not Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS Not Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS Not Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS Not Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS Not Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS Not Available

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