For research use only. Not for therapeutic Use.
TLK117, the active metabolite of TLK199, selective inhibits Glutathione S-transferase P1–1 (GSTP1-1) with a Ki of 0.4 μM for GSTP. TLK117 also competitively inhibits glyoxalase I with a Ki of 0.56 μM.
TLK117 is the most specific GSTP inhibitor to date, with a binding affinity greater than GSH itself and a selectivity for GSTP over 50-fold greater than the GSTM and GSTA classes (Ki=0.4 μM)[1]. TER 117 is developed as a GST P1-1 isoenzyme inhibitor to circumvent the indicated contribution of GST P1-1 to drug resistance of tumor cells. To facilitate the cellular uptake of TER 117, it is delivered as a diethyl ester (TER 117 DEE, also called TER 199). TER 117 is found to be a competitive inhibitor of both GST P1-1 and glyoxalase I[2].
Oropharyngeal administration of the GSTP inhibitor, TLK117, at a time when fibrosis is already apparent, attenuated bleomycin- and AdTGFβ-induced remodeling, α-SMA, caspase activation, FAS S-glutathionylation, and total protein S-glutathionylation. Four hours after administration of 50 mg/kg TLK117, GSTP activity is strongly decreased and remains decreased by about 60% for at least 24 hours[2].
| Catalog Number | I020227 |
| CAS Number | 152684-53-2 |
| Synonyms | (2S)-2-amino-5-[[(2R)-3-benzylsulfanyl-1-[[(R)-carboxy(phenyl)methyl]amino]-1-oxopropan-2-yl]amino]-5-oxopentanoic acid |
| Molecular Formula | C23H27N3O6S |
| Purity | ≥95% |
| InChI | 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 |
| InChIKey | ZPSKWMFLCHMEOY-CMKODMSKSA-N |
| SMILES | C1=CC=C(C=C1)CSCC(C(=O)NC(C2=CC=CC=C2)C(=O)O)NC(=O)CCC(C(=O)O)N |
| Reference | [1]. The human glutathione transferase P1-1 specific inhibitor TER 117 designed for overcomingcytostatic-drug resistance is also a strong inhibitor of glyoxalase I. Mol Pharmacol. 2000 Mar;57(3):619-24. [2]. McMillan DH, et al. Attenuation of lung fibrosis in mice with a clinically relevant inhibitor of glutathione-S-transferase π. JCI Insight. 2016 Jun 2;1(8). pii: e85717. |
