TLK117, the active metabolite of TLK199, selective inhibits Glutathione S-transferase P1–1 (GSTP1-1) with a K_i of 0.4 μM for GSTP. TLK117 also competitively inhibits glyoxalase I with a K_i of 0.56 μM.

Ki: 0.4 μM^[1], 0.56 μM (glyoxalase I)^[2]

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 (K_i=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].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

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].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

473.54

C₂₃H₂₇N₃O₆S

152684-53-2

Room temperature in continental US; may vary elsewhere.

Powder	-20°C	3 years
	4°C	2 years
In solvent	-80°C	6 months
	-20°C	1 month

In Vitro: 

DMSO : 150 mg/mL (316.76 mM; Need ultrasonic)

*

请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。
储备液的保存方式和期限：-80°C, 6 months; -20°C, 1 month。-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。

In Vivo:

请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照 In Vitro 方式配制澄清的储备液，再依次添加助溶剂：

——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用； 以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶

• 1.

  请依序添加每种溶剂： 10% DMSO    40% PEG300    5% Tween-80    45% saline

  Solubility: ≥ 2.5 mg/mL (5.28 mM); Clear solution

  此方案可获得 ≥ 2.5 mg/mL (5.28 mM，饱和度未知) 的澄清溶液。

  以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；向上述体系中加入50 μL Tween-80，混合均匀；然后继续加入 450 μL生理盐水定容至 1 mL。

  将 0.9 g 氯化钠，完全溶解于 100 mL ddH₂O 中，得到澄清透明的生理盐水溶液

• 2.

  请依序添加每种溶剂： 10% DMSO    90% (20% SBE-β-CD in saline)

  Solubility: ≥ 2.5 mg/mL (5.28 mM); Clear solution

  此方案可获得 ≥ 2.5 mg/mL (5.28 mM，饱和度未知) 的澄清溶液。

  以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL 20% 的 SBE-β-CD 生理盐水水溶液中，混合均匀。

  将 2 g 磺丁基醚 β-环糊精加入 5 mL 生理盐水中，再用生理盐水定容至 10 mL，完全溶解，澄清透明
• 3.

  请依序添加每种溶剂： 10% DMSO    90% corn oil

  Solubility: ≥ 2.5 mg/mL (5.28 mM); Clear solution

  此方案可获得 ≥ 2.5 mg/mL (5.28 mM，饱和度未知) 的澄清溶液，此方案不适用于实验周期在半个月以上的实验。

  以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。

• [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.

The potency of TER 117 in the inhibition of GST P1-1/Ile-105 and GST P1-1/Val-105 is determined by means of GSH competition experiments using 1 μM TER 117 and three different fixed concentrations of GSH: 0.2, 0.6, and 2.0 mM. The concentration of the second substrate, 1-chloro-2,4-dinitrobenzene (CDNB) ranged between 0.15 and 1.8 mM. In addition, the inhibitor is tested at different concentrations, 0 to 8 μM, at a CDNB concentration of 1 mM and the above GSH concentrations. Initial velocities are determined spectrophotometrically at 30°C. The conjugation reaction between GSH and CDNB is monitored at 340 nm in 1 mL of 0.1 M sodium phosphate, pH 7.0^[2].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

Mice^[1]

TLK117 is administered oropharyngeally at a dose of 50 mg/kg in a 0.375 M Tris-HCl solution, pH =7.4, with 0.02% DMSO. This Tris-HCl/DMSO solution is used as a vehicle control. Treatments are performed once every 3 days from day 14 to day 26 in both >bleomycin and AdTGFβ models

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

• [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.