NAV

Ezatiostat

Identification

Generic Name
Ezatiostat
DrugBank Accession Number
DB05460
Background

Ezatiostat is investigated in clinical trials for treating myelodysplastic syndrome. This compound belongs to the peptides. These are compounds containing an amide derived from two or more amino carboxylic acid molecules (the same or different) by formation of a covalent bond from the carbonyl carbon of one to the nitrogen atom of another. This medication is known to target Glutathione S-transferase P. Ezatiostat is a small molecule drug that is an analog inhibitor of glutathione S-transferase P1-1. It acts intracellularly on the MAPK signaling pathway by activating ERK2. Ezatiostat has myelostimulant activity in preclinical rodent models and human bone marrow cultures, and differentiates granulocytes and monocytes in HL60 cells. Ezatiostat is a candidate designed to stimulate the formation of bone marrow cells that are precursors to granulocytes and monocytes (white blood cells), erythrocytes (red blood cells) and platelets. Many conditions are characterized by depleted bone marrow, including myelodysplastic syndrome (MDS), a form of pre-leukemia in which the bone marrow produces insufficient levels of one or more of the 3 major blood elements (white blood cells, red blood cells and platelets). It might also be relevant as an adjunct therapy since a reduction in blood cell levels is also a common, toxic effect of many standard chemotherapeutic drugs.

Type
Small Molecule
Groups
Investigational
Structure
MOL SDF PDB SMILES InChI
Similar Structures
Weight
Average: 529.648
Monoisotopic: 529.224656557
Chemical Formula
C27H35N3O6S
Synonyms
  • Ezatiostat
  • gamma-Glutamyl-S-(benzyl)-cysteinyl-R(-)-phenylglycine diethyl ester
External IDs
  • TER 199
  • Ter-199
  • Terrapin 199
  • TLK-199
  • TLK199

Pharmacology

Indication

Investigated for use/treatment in myelodysplastic syndrome.

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Pharmacodynamics

Not Available

Mechanism of action
Target Actions Organism
UGlutathione S-transferase P Not Available Humans
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);">
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

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Product Ingredients
Ingredient UNII CAS InChI Key
Ezatiostat hydrochloride D59N834676 286942-97-0 XJDYQYNYISTAMO-GFDYFVENSA-N
International/Other Brands
Telintra

Categories

Drug Categories
Chemical TaxonomyProvided byClassyfire
Description
这种化合物属于类的有机排版ounds known as oligopeptides. These are organic compounds containing a sequence of between three and ten alpha-amino acids joined by peptide bonds.
Kingdom
Organic compounds
Super Class
Organic acids and derivatives
Class
Carboxylic acids and derivatives
Sub Class
Amino acids, peptides, and analogues
Direct Parent
Oligopeptides
Alternative Parents
Glutamine and derivatives/Alpha amino acid esters/N-acyl-alpha amino acids and derivatives/Alpha amino acid amides/Cysteine and derivatives/Fatty acid esters/N-acyl amines/Dicarboxylic acids and derivatives/Benzene and substituted derivatives/Carboxylic acid esters
show 8 more
Substituents
Alpha-amino acid amide/Alpha-amino acid ester/Alpha-amino acid or derivatives/Alpha-oligopeptide/Amine/Amino acid or derivatives/Aromatic homomonocyclic compound/Benzenoid/Carbonyl group/Carboxamide group
show 25 more
Molecular Framework
Aromatic homomonocyclic compounds
External Descriptors
Not Available
Affected organisms
Not Available

Chemical Identifiers

UNII
057D10I8S8
CAS number
168682-53-9
InChI Key
GWEJFLVSOGNLSS-WPFOTENUSA-N
InChI
InChI=1S/C27H35N3O6S/c1-3-35-26(33)21(28)15-16-23(31)29-22(18-37-17-19-11-7-5-8-12-19)25(32)30-24(27(34)36-4-2)20-13-9-6-10-14-20/h5-14,21-22,24H,3-4,15-18,28H2,1-2H3,(H,29,31)(H,30,32)/t21-,22-,24+/m0/s1
IUPAC Name
ethyl (2S)-2-amino-4-{[(1R)-2-(benzylsulfanyl)-1-{[(1R)-2-ethoxy-2-oxo-1-phenylethyl]carbamoyl}ethyl]carbamoyl}butanoate
SMILES
CCOC(=O)[C@@H](N)CCC(=O)N[C@@H](CSCC1=CC=CC=C1)C(=O)N[C@@H](C(=O)OCC)C1=CC=CC=C1

References

一般引用
  1. Hamilton D, Batist G: TLK-199 (Telik). IDrugs. 2005 Aug;8(8):662-9. [Article]
PubChem Compound
5310939
PubChem Substance
175427010
ChemSpider
4470493
ChEMBL
CHEMBL2110585
ZINC
ZINC000056898832

Clinical Trials

Clinical TrialsLearn More" title="" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count
2 Completed Treatment Myelodysplastic Syndrome (MDS) 1
2 Terminated Supportive Care Lung Cancer Non-Small Cell Cancer (NSCLC) 1
2 Terminated Treatment Myelodysplastic Syndrome (MDS) 2
2 Terminated Treatment Neutropenia, Severe Chronic 1
1 Completed Treatment Myelodysplastic Syndrome (MDS) 1
1, 2 Completed Treatment Myelodysplastic Syndrome (MDS) 2

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 0.00245 mg/mL ALOGPS
logP 2.39 ALOGPS
logP 2.42 Chemaxon
logS -5.3 ALOGPS
pKa (Strongest Acidic) 11.75 Chemaxon
pKa (Strongest Basic) 7.18 Chemaxon
Physiological Charge 1 Chemaxon
Hydrogen Acceptor Count 5 Chemaxon
Hydrogen Donor Count 3 Chemaxon
Polar Surface Area 136.82 Å2 Chemaxon
Rotatable Bond Count 17 Chemaxon
Refractivity 141.82 m3·mol-1 Chemaxon
Polarizability 57.51 Å3 Chemaxon
Number of Rings 2 Chemaxon
Bioavailability 0 Chemaxon
Rule of Five No Chemaxon
Ghose Filter No Chemaxon
Veber's Rule No Chemaxon
MDDR-like规则 No Chemaxon
Predicted ADMET Features
Property Value Probability
Human Intestinal Absorption + 0.932
Blood Brain Barrier + 0.5139
Caco-2 permeable - 0.7903
P-glycoprotein substrate Substrate 0.7299
P-glycoprotein inhibitor I Inhibitor 0.5322
P-glycoprotein inhibitor II Non-inhibitor 0.9937
Renal organic cation transporter Non-inhibitor 0.8903
CYP450 2C9 substrate Non-substrate 0.8782
CYP450 2D6 substrate Non-substrate 0.8538
CYP450 3A4 substrate Non-substrate 0.5726
CYP450 1A2 substrate Non-inhibitor 0.9101
CYP450 2C9 inhibitor Non-inhibitor 0.8228
CYP450 2D6 inhibitor Non-inhibitor 0.766
CYP450 2C19 inhibitor Non-inhibitor 0.6553
CYP450 3A4 inhibitor Inhibitor 0.5834
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.704
Ames test Non AMES toxic 0.778
Carcinogenicity Non-carcinogens 0.8939
Biodegradation Not ready biodegradable 0.9409
Rat acute toxicity 2.2434 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.9864
hERG inhibition (predictor II) Non-inhibitor 0.7148
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 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

Targets

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Details 1.Glutathione S-transferase P
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
S-nitrosoglutathione binding
Specific Function
Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles. Regulates negatively CDK5 activity via p25/p35 translocation to prevent neurodegeneration.
Gene Name
GSTP1
Uniprot ID
P09211
Uniprot Name
Glutathione S-transferase P
分子量
23355.625 Da
References
  1. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [Article]

Drug created at November 18, 2007 18:25 / Updated at December 13, 2022 10:46