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MedKoo Cat#: 201360 | Name: Ezatiostat
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Description:

WARNING: This product is for research use only, not for human or veterinary use.

Ezatiostat is a liposomal small-molecule glutathione analog inhibitor of glutathione S-transferase (GST) P1-1 with hematopoiesis-stimulating activity. After intracellular de-esterification, the active form of ezatiostat binds to and inhibits GST P1-1, thereby restoring Jun kinase and MAPK pathway activities and promoting MAPK-mediated cellular proliferation and differentiation pathways. This agent promotes the proliferation and maturation of hematopoietic precursor cells, granulocytes, monocytes, erythrocytes and platelets. Check for active clinical trials or closed clinical trials using this agent. (NCI Thesaurus).

Chemical Structure

Ezatiostat
Ezatiostat
CAS#168682-53-9 (free base)

Theoretical Analysis

MedKoo Cat#: 201360

Name: Ezatiostat

CAS#: 168682-53-9 (free base)

Chemical Formula: C27H35N3O6S

Exact Mass: 529.2247

Molecular Weight: 529.65

Elemental Analysis: C, 61.23; H, 6.66; N, 7.93; O, 18.12; S, 6.05

Price and Availability

Size Price Availability Quantity
5mg USD 110.00 Ready to ship
10mg USD 180.00 Ready to ship
25mg USD 385.00 Ready to ship
50mg USD 685.00 Ready to ship
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Related CAS #
168682-53-9 (free base) 286942-97-0 (HCl)
Synonym
TLK199; TLK-199; TLK 199; Ezatiostat; Brand name: TELINTRA
IUPAC/Chemical Name
(S)-ethyl 2-amino-5-(((R)-3-(benzylthio)-1-(((S)-2-ethoxy-2-oxo-1-phenylethyl)amino)-1-oxopropan-2-yl)amino)-5-oxopentanoate
InChi Key
GWEJFLVSOGNLSS-FIXSFTCYSA-N
InChi Code
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
SMILES Code
O=C(OCC)[C@@H](N)CCC(N[C@@H](CSCC1=CC=CC=C1)C(N[C@@H](C2=CC=CC=C2)C(OCC)=O)=O)=O
Appearance
White solid powder
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO, not in water
Shelf Life
>2 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
More Info
Related CAS# 168682-53-9 (Ezatiostat); 286942-97-0 (Ezatiostat HCl salt)  
Biological target:
Ezatiostat (TER199, TLK199, Telintra), a tripeptide analog of glutathione, is a peptidomimetic inhibitor of Glutathione S-transferase P1-1 (GSTP1-1).
In vitro activity:
The IC50 values were 22 μM for TLK199 in HT29 human colon adenocarcinoma cells line that express high levels of GSTP1-1. Similar IC50 values (26–28 μM) for TLK199 were obtained with other human colon adenocarcinoma cell lines, e.g., SW620, LoVo, and Caco2. TLK199 is easily taken up by the cells, rapidly converted to phenylglycine monoethyl ester TLK236, and then gradually converted to TLK117. TLK199 undergoes deesterification to glutamyl monoethyl ester TLK235 as well, but this metabolite is only produced in very limited quantities (Figs. 1 and 2). Reference: Handb Exp Pharmacol. 2021;264:71-91. https://dx.doi.org/10.1007/164_2020_392
In vivo activity:
The absorption, distribution, metabolism, and elimination properties of TLK199 were characterized in rat and dog. The primary metabolites are TLK236 and TLK117. Unchanged TLK199 was not detected in the blood, although the metabolites TLK117 and TLK236 were, indicating that the systemic clearance of the parent compound was both rapid and extensive. TLK199 has a half-life in rodents of <1 min and in monkeys of ~15 min. Reference: Handb Exp Pharmacol. 2021;264:71-91. https://dx.doi.org/10.1007/164_2020_392
Solvent mg/mL mM
Solubility
DMSO 100.0 155.36
Ethanol 15.0 23.30
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 529.65 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol:
In vitro protocol:
1. Zhang J, Ye ZW, Janssen-Heininger Y, Townsend DM, Tew KD. Development of Telintra as an Inhibitor of Glutathione S-Transferase P. Handb Exp Pharmacol. 2021;264:71-91. doi: 10.1007/164_2020_392. PMID: 32767141. 2. Ruscoe JE, Rosario LA, Wang T, Gaté L, Arifoglu P, Wolf CR, Henderson CJ, Ronai Z, Tew KD. Pharmacologic or genetic manipulation of glutathione S-transferase P1-1 (GSTpi) influences cell proliferation pathways. J Pharmacol Exp Ther. 2001 Jul;298(1):339-45. PMID: 11408560.
In vivo protocol:
1. Zhang J, Ye ZW, Janssen-Heininger Y, Townsend DM, Tew KD. Development of Telintra as an Inhibitor of Glutathione S-Transferase P. Handb Exp Pharmacol. 2021;264:71-91. doi: 10.1007/164_2020_392. PMID: 32767141. 2. Ruscoe JE, Rosario LA, Wang T, Gaté L, Arifoglu P, Wolf CR, Henderson CJ, Ronai Z, Tew KD. Pharmacologic or genetic manipulation of glutathione S-transferase P1-1 (GSTpi) influences cell proliferation pathways. J Pharmacol Exp Ther. 2001 Jul;298(1):339-45. PMID: 11408560.
1: Mahadevan D, Sutton GR. Ezatiostat hydrochloride for the treatment of myelodysplastic syndromes. Expert Opin Investig Drugs. 2015 May;24(5):725-33. doi: 10.1517/13543784.2015.1021003. Epub 2015 Feb 27. PMID: 25724698. 2: Wang SQ, Chen JJ, Jiang Y, Lei ZN, Ruan YC, Pan Y, Yam JWP, Wong MP, Xiao ZJ. Targeting GSTP1 as Therapeutic Strategy against Lung Adenocarcinoma Stemness and Resistance to Tyrosine Kinase Inhibitors. Adv Sci (Weinh). 2023 Mar;10(7):e2205262. doi: 10.1002/advs.202205262. Epub 2023 Jan 29. PMID: 36709476; PMCID: PMC9982593. 3: Quddus F, Clima J, Seedham H, Sajjad G, Galili N, Raza A. Oral Ezatiostat HCl (TLK199) and Myelodysplastic syndrome: a case report of sustained hematologic response following an abbreviated exposure. J Hematol Oncol. 2010 Apr 23;3:16. doi: 10.1186/1756-8722-3-16. PMID: 20416051; PMCID: PMC2873355. 4: Galili N, Tamayo P, Botvinnik OB, Mesirov JP, Brooks MR, Brown G, Raza A. Prediction of response to therapy with ezatiostat in lower risk myelodysplastic syndrome. J Hematol Oncol. 2012 May 6;5:20. doi: 10.1186/1756-8722-5-20. PMID: 22559819; PMCID: PMC3407785. 5: Raza A, Galili N, Mulford D, Smith SE, Brown GL, Steensma DP, Lyons RM, Boccia R, Sekeres MA, Garcia-Manero G, Mesa RA. Phase 1 dose-ranging study of ezatiostat hydrochloride in combination with lenalidomide in patients with non- deletion (5q) low to intermediate-1 risk myelodysplastic syndrome (MDS). J Hematol Oncol. 2012 Apr 30;5:18. doi: 10.1186/1756-8722-5-18. PMID: 22546242; PMCID: PMC3416694. 6: Raza A, Galili N, Callander N, Ochoa L, Piro L, Emanuel P, Williams S, Burris H 3rd, Faderl S, Estrov Z, Curtin P, Larson RA, Keck JG, Jones M, Meng L, Brown GL. Phase 1-2a multicenter dose-escalation study of ezatiostat hydrochloride liposomes for injection (Telintra, TLK199), a novel glutathione analog prodrug in patients with myelodysplastic syndrome. J Hematol Oncol. 2009 May 13;2:20. doi: 10.1186/1756-8722-2-20. PMID: 19439093; PMCID: PMC2694211. 7: Raza A, Galili N, Smith S, Godwin J, Lancet J, Melchert M, Jones M, Keck JG, Meng L, Brown GL, List A. Phase 1 multicenter dose-escalation study of ezatiostat hydrochloride (TLK199 tablets), a novel glutathione analog prodrug, in patients with myelodysplastic syndrome. Blood. 2009 Jun 25;113(26):6533-40. doi: 10.1182/blood-2009-01-176032. Epub 2009 Apr 27. PMID: 19398716. 8: Raza A, Galili N, Smith SE, Godwin J, Boccia RV, Myint H, Mahadevan D, Mulford D, Rarick M, Brown GL, Schaar D, Faderl S, Komrokji RS, List AF, Sekeres M. A phase 2 randomized multicenter study of 2 extended dosing schedules of oral ezatiostat in low to intermediate-1 risk myelodysplastic syndrome. Cancer. 2012 Apr 15;118(8):2138-47. doi: 10.1002/cncr.26469. Epub 2011 Sep 1. PMID: 21887679. 9: Steensma DP. Novel therapies for myelodysplastic syndromes. Hematol Oncol Clin North Am. 2010 Apr;24(2):423-41. doi: 10.1016/j.hoc.2010.02.010. PMID: 20359635. 10: Lyons RM, Wilks ST, Young S, Brown GL. Oral ezatiostat HCl (Telintra®, TLK199) and idiopathic chronic neutropenia (ICN): a case report of complete response of a patient with G-CSF resistant ICN following treatment with ezatiostat, a glutathione S-transferase P1-1 (GSTP1-1) inhibitor. J Hematol Oncol. 2011 Nov 2;4:43. doi: 10.1186/1756-8722-4-43. PMID: 22047626; PMCID: PMC3235963. 11: Zhang J, Ye ZW, Janssen-Heininger Y, Townsend DM, Tew KD. Development of Telintra as an Inhibitor of Glutathione S-Transferase P. Handb Exp Pharmacol. 2021;264:71-91. doi: 10.1007/164_2020_392. PMID: 32767141; PMCID: PMC8963531. 12: D'Alò F, Greco M, Criscuolo M, Voso MT. New treatments for myelodysplastic syndromes. Mediterr J Hematol Infect Dis. 2010 Aug 11;2(2):e2010021. doi: 10.4084/MJHID.2010.021. PMID: 21415972; PMCID: PMC3033133. 13: Zhao S, Wang B, Zhong Z, Liu T, Liang T, Zhan J. Contributions of enzymes and gut microbes to biotransformation of perfluorooctane sulfonamide in earthworms (Eisenia fetida). Chemosphere. 2020 Jan;238:124619. doi: 10.1016/j.chemosphere.2019.124619. Epub 2019 Aug 19. PMID: 31450114. 14: Faccidomo S, Swaim KS, Saunders BL, Santanam TS, Taylor SM, Kim M, Reid GT, Eastman VR, Hodge CW. Mining the nucleus accumbens proteome for novel targets of alcohol self-administration in male C57BL/6J mice. Psychopharmacology (Berl). 2018 Jun;235(6):1681-1696. doi: 10.1007/s00213-018-4870-3. Epub 2018 Mar 3. PMID: 29502276; PMCID: PMC5949261. 15: Llavanera M, Mateo-Otero Y, Delgado-Bermúdez A, Recuero S, Olives S, Barranco I, Yeste M. Deactivation of the JNK Pathway by GSTP1 Is Essential to Maintain Sperm Functionality. Front Cell Dev Biol. 2021 Feb 25;9:627140. doi: 10.3389/fcell.2021.627140. PMID: 33732696; PMCID: PMC7959831.

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