TLK117 is an inhibitor of GSTs that reduces the severity of pulmonary fibrosis and can be used to study idiopathic pulmonary fibrosis.

aldolase I:0.56 μM (Ki), glutathione S-transferase P:0.4 μM (Ki)

TLK117 is a potent and specific glutathione S-transferase P (GSTP) inhibitor with a higher binding affinity to the target than glutathione (GSH) and more than 50-fold selectivity for GSTP compared to GSTM and GSTA classes, with a constant of inhibition (Ki) of 0.4 μM.[1]
TLK117 was developed as an inhibitor of the GST P1-1 isoenzyme to address the critical role of GST P1-1 in drug resistance in tumor cells. To enhance the cellular uptake efficiency of TLK117, the compound is delivered as a diethyl ester (TER 117 DEE, also known as TER 199).TLK117 competitively inhibits GST P1-1 and aldolase I. The inhibition constant (Ki) of TLK117 on aldolase I is 0.56 μM.[2]

In cases where fibrosis has already formed, TLK117 attenuates pathological changes by inhibiting GSTP to attenuate tissue remodeling induced by bleomycin and adenoviral TGFβ (AdTGFβ), and decreasing the levels of α-SMA, cysteine asparaginase activity, FAS S-glutathionylation, and total protein S-glutathionylation. Within 4 hours after administration of 50 mg/kg TLK117, GSTP activity was substantially reduced and maintained at approximately 60% inhibition for at least 24 hours. [2]