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Details

Stereochemistry ABSOLUTE
Molecular Formula C23H27N3O6S
Molecular Weight 473.542
Optical Activity UNSPECIFIED
Defined Stereocenters 3 / 3
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of TLK-117

SMILES

N[C@@H](CCC(=O)N[C@@H](CSCC1=CC=CC=C1)C(=O)N[C@@H](C(O)=O)C2=CC=CC=C2)C(O)=O

InChI

InChIKey=ZPSKWMFLCHMEOY-CMKODMSKSA-N
InChI=1S/C23H27N3O6S/c24-17(22(29)30)11-12-19(27)25-18(14-33-13-15-7-3-1-4-8-15)21(28)26-20(23(31)32)16-9-5-2-6-10-16/h1-10,17-18,20H,11-14,24H2,(H,25,27)(H,26,28)(H,29,30)(H,31,32)/t17-,18-,20+/m0/s1

HIDE SMILES / InChI

Molecular Formula C23H27N3O6S
Molecular Weight 473.542
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 3 / 3
E/Z Centers 0
Optical Activity UNSPECIFIED

Ezatiostat (TLK199) [γ-glutamyl-S-(benzyl)cysteinyl-R-phenyl glycine diethyl ester] is an inhibitor of Glutathione S-transferase P1–1 (GSTπ). The drug is a peptidomimetic of GSH (glutathione), esterified to enhance cellular uptake and designed to bind to the “G-site” of GSTP1–1. Independent of catalysis inhibition, TLK199 also disrupts the protein:protein interaction site(s) between GSTP1–1 and JNK1. Telik Inc was developing TLK-199 for the potential prevention of myelosuppression in blood diseases, namely myelodysplastic syndrome.

Originator

Curator's Comment: reference retrieved from https://www.ncbi.nlm.nih.gov/pubmed/11408560

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
400.0 nM [Ki]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
Doses

Doses

DosePopulationAdverse events​
3000 mg 2 times / day multiple, oral
Highest studied dose
Dose: 3000 mg, 2 times / day
Route: oral
Route: multiple
Dose: 3000 mg, 2 times / day
Sources: Page: p.6537
unhealthy
n = 12
Health Status: unhealthy
Condition: myelodysplastic syndrome
Sex: M+F
Food Status: UNKNOWN
Population Size: 12
Sources: Page: p.6537
Disc. AE: Nausea...
AEs leading to
discontinuation/dose reduction:
Nausea (8.3%)
Sources: Page: p.6537
AEs

AEs

AESignificanceDosePopulation
Nausea 8.3%
Disc. AE
3000 mg 2 times / day multiple, oral
Highest studied dose
Dose: 3000 mg, 2 times / day
Route: oral
Route: multiple
Dose: 3000 mg, 2 times / day
Sources: Page: p.6537
unhealthy
n = 12
Health Status: unhealthy
Condition: myelodysplastic syndrome
Sex: M+F
Food Status: UNKNOWN
Population Size: 12
Sources: Page: p.6537
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
Pharmacologic or genetic manipulation of glutathione S-transferase P1-1 (GSTpi) influences cell proliferation pathways.
2001 Jul
Glutathione-S-transferase P1-1 protects aberrant crypt foci from apoptosis induced by deoxycholic acid.
2004 Aug
TLK-199 (Telik).
2005 Aug
Patents

Sample Use Guides

Phase 1 testing of ezatiostat, a glutathione S-transferase P1-1 inhibitor, for the treatment of myelodysplastic syndrome was conducted in a multidose-escalation study. Patients received 10 dose levels (200, 400, 1000, 1400, 2000, 2400, 3000, 4000, 5000, and 6000 mg) of ezatiostat tablets in divided doses on days 1 to 7 of a 21-day cycle for a maximum of 8 cycles. Ezatiostat hydrochloride liposomes for injection, a glutathione S-transferase P1-1 inhibitor, was evaluated in myelodysplastic syndrome (MDS). The objectives were to determine the safety, pharmacokinetics, and hematologic improvement (HI) rate. Phase 1-2a testing of ezatiostat for the treatment of MDS was conducted in a multidose-escalation, multicenter study. Phase 1 patients received ezatiostat at 5 dose levels (50, 100, 200, 400 and 600 mg/m2) intravenously (IV) on days 1 to 5 of a 14-day cycle until MDS progression or unacceptable toxicity. In phase 2, ezatiostat was administered on 2 dose schedules: 600 mg/m2 IV on days 1 to 5 or days 1 to 3 of a 21-day treatment cycle.
Route of Administration: Other
Wild type HL60 cells were induced to undergo apoptosis by 8- and 24-h treatments with 10 and 50 uM ezatiostat (TLK199). Additive apoptotic effects were seen when HL60 cells were co-treated with 50 uM TLK199 and UV.
Substance Class Chemical
Created
by admin
on Fri Jul 07 00:53:41 UTC 2023
Edited
by admin
on Fri Jul 07 00:53:41 UTC 2023
Record UNII
LJ5T8BSZ4G
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
TLK-117
Code English
TER-117
Code English
TER117
Code English
Glycine, L-γ-glutamyl-S-(phenylmethyl)-L-cysteinyl-2-phenyl-, (2R)-
Systematic Name English
(2R)-L-γ-Glutamyl-S-(phenylmethyl)-L-cysteinyl-2-phenylglycine
Systematic Name English
Glycine, N-[N-L-γ-glutamyl-S-(phenylmethyl)-L-cysteinyl]-D-2-phenyl-
Systematic Name English
TLK117
Code English
Code System Code Type Description
FDA UNII
LJ5T8BSZ4G
Created by admin on Fri Jul 07 00:53:41 UTC 2023 , Edited by admin on Fri Jul 07 00:53:41 UTC 2023
PRIMARY
CAS
152684-53-2
Created by admin on Fri Jul 07 00:53:41 UTC 2023 , Edited by admin on Fri Jul 07 00:53:41 UTC 2023
PRIMARY
PUBCHEM
444051
Created by admin on Fri Jul 07 00:53:41 UTC 2023 , Edited by admin on Fri Jul 07 00:53:41 UTC 2023
PRIMARY
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