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Identification
NameTLK-199
Accession NumberDB05460
TypeSmall Molecule
GroupsInvestigational
Description

TLK-199 is investigated in clinical trials for treating myelodysplastic syndrome. TLK-199 is a solid. 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. TLK-199 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. TLK-199 has myelostimulant activity in preclinical rodent models and human bone marrow cultures, and differentiates granulocytes and monocytes in HL60 cells. TLK-199 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.

Structure
Thumb
SynonymsNot Available
External Identifiers Not Available
Approved Prescription ProductsNot Available
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
TelintraNot Available
Brand mixturesNot Available
SaltsNot Available
CategoriesNot Available
UNIINot Available
CAS numberNot Available
WeightAverage: 529.648
Monoisotopic: 529.224656557
Chemical FormulaC27H35N3O6S
InChI KeyInChIKey=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
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as 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.
KingdomOrganic compounds
Super ClassOrganic acids and derivatives
ClassCarboxylic acids and derivatives
Sub ClassAmino acids, peptides, and analogues
Direct ParentPeptides
Alternative Parents
Substituents
  • Alpha peptide
  • N-acyl-alpha amino acid or derivatives
  • Alpha-amino acid ester
  • Alpha-amino acid amide
  • Phenylacetate
  • Alpha-amino acid or derivatives
  • N-substituted-alpha-amino acid
  • Fatty acid ester
  • Fatty acyl
  • Benzenoid
  • N-acyl-amine
  • Fatty amide
  • Dicarboxylic acid or derivatives
  • Monocyclic benzene moiety
  • Secondary carboxylic acid amide
  • Carboxylic acid ester
  • Carboxamide group
  • Dialkylthioether
  • Sulfenyl compound
  • Thioether
  • Carboxylic acid amide
  • Hydrocarbon derivative
  • Primary amine
  • Organosulfur compound
  • Organooxygen compound
  • Organonitrogen compound
  • Primary aliphatic amine
  • Carbonyl group
  • Amine
  • Aromatic homomonocyclic compound
Molecular FrameworkAromatic homomonocyclic compounds
External DescriptorsNot Available
Pharmacology
IndicationInvestigated for use/treatment in myelodysplastic syndrome.
PharmacodynamicsNot Available
Mechanism of actionNot Available
Related Articles
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingNot Available
MetabolismNot Available
Route of eliminationNot Available
Half lifeNot Available
ClearanceNot Available
ToxicityNot Available
Affected organismsNot Available
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.932
Blood Brain Barrier+0.5139
Caco-2 permeable-0.7903
P-glycoprotein substrateSubstrate0.7299
P-glycoprotein inhibitor IInhibitor0.5322
P-glycoprotein inhibitor IINon-inhibitor0.9937
Renal organic cation transporterNon-inhibitor0.8903
CYP450 2C9 substrateNon-substrate0.8782
CYP450 2D6 substrateNon-substrate0.8538
CYP450 3A4 substrateNon-substrate0.5726
CYP450 1A2 substrateNon-inhibitor0.9101
CYP450 2C9 inhibitorNon-inhibitor0.8228
CYP450 2D6 inhibitorNon-inhibitor0.766
CYP450 2C19 inhibitorNon-inhibitor0.6553
CYP450 3A4 inhibitorInhibitor0.5834
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.704
Ames testNon AMES toxic0.778
CarcinogenicityNon-carcinogens0.8939
BiodegradationNot ready biodegradable0.9409
Rat acute toxicity2.2434 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9864
hERG inhibition (predictor II)Non-inhibitor0.7148
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
StateSolid
Experimental PropertiesNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.00245 mg/mLALOGPS
logP2.39ALOGPS
logP2.42ChemAxon
logS-5.3ALOGPS
pKa (Strongest Acidic)11.8ChemAxon
pKa (Strongest Basic)7.18ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area136.82 Å2ChemAxon
Rotatable Bond Count17ChemAxon
Refractivity141.82 m3·mol-1ChemAxon
Polarizability57.5 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability0ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis ReferenceNot Available
General References
  1. Hamilton D, Batist G: TLK-199 (Telik). IDrugs. 2005 Aug;8(8):662-9. [PubMed:16044376 ]
External Links
ATC CodesNot Available
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Human
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
Molecular Weight:
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. [PubMed:10592235 ]
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Drug created on November 18, 2007 11:25 / Updated on September 23, 2014 14:10