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
Structure for Ezatiostat (DB05460)
- 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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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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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
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- 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 by Classyfire
- Description
- This compound belongs to the class of organic compounds 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
- General References
- Hamilton D, Batist G: TLK-199 (Telik). IDrugs. 2005 Aug;8(8):662-9. [Article]
- External Links
- PubChem Compound
- 5310939
- PubChem Substance
- 175427010
- ChemSpider
- 4470493
- ChEMBL
- CHEMBL2110585
- ZINC
- ZINC000056898832
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 2 Completed Treatment Myelodysplastic Syndrome 1 2 Terminated Supportive Care Non-Small Cell Lung Cancer (NSCLC) 1 2 Terminated Treatment Myelodysplastic Syndrome 2 2 Terminated Treatment Severe Chronic Neutropenia 1 1 Completed Treatment Myelodysplastic Syndrome 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 0.00245 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 Rule 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
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 222.00343 predictedDeepCCS 1.0 (2019) [M+H]+ 223.89891 predictedDeepCCS 1.0 (2019) [M+Na]+ 229.97371 predictedDeepCCS 1.0 (2019)
Targets
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- 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
- Molecular Weight
- 23355.625 Da
References
- 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