TLK197 is the bioactive metabolite of TLK199, selectively inhibits glutathione S-transferase P1-1 (GSTP1-1), and binds GSTP with a Ki of 0.4 μM. TLK117 also competitively inhibits glyoxalase I with a Ki of 0.56 μM.

Physicochemical Properties

Molecular Formula	C23H27N3O6S
Molecular Weight	473.541984796524
Exact Mass	473.162
CAS #	152684-53-2
Related CAS #	Ezatiostat;168682-53-9
PubChem CID	444051
Appearance	White to off-white solid powder
LogP	-0.9
Hydrogen Bond Donor Count	5
Hydrogen Bond Acceptor Count	8
Rotatable Bond Count	13
Heavy Atom Count	33
Complexity	665
Defined Atom Stereocenter Count	3
SMILES	[C@@H](C1C=CC=CC=1)(C(=O)O)NC(=O)[C@H](CSCC1C=CC=CC=1)NC(=O)CC[C@H](N)C(=O)O
InChi Key	ZPSKWMFLCHMEOY-CMKODMSKSA-N
InChi Code	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
Chemical Name	(2S)-2-amino-5-[[(2R)-3-benzylsulfanyl-1-[[(R)-carboxy(phenyl)methyl]amino]-1-oxopropan-2-yl]amino]-5-oxopentanoic acid
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

Targets	Ki: 0.4 μM[1], 0.56 μM (glyoxalase I)[2]
ln Vitro	With a binding affinity greater than GSH and a selectivity for GSTP that is over 50 times greater than that of the GSTM and GSTA classes (Ki=0.4 μM), TLK117 is the most specific GSTP inhibitor found to date[1]. TER 117 is a GST P1-1 isoenzyme inhibitor designed to avoid the known role of GST P1-1 in tumor cells' resistance to drugs. TER 117 is administered as a diethyl ester (TER 117 DEE, also known as TER 199) to aid in its cellular uptake. It has been discovered that TER 117 is a competitive inhibitor of glyoxalase I and GST P1-1[2].
ln Vivo	When the GSTP inhibitor TLK117 is administered orally during the pharyngeal stage of fibrosis, it reduces the amount of remodeling caused by bleomycin and AdTGFβ, α-SMA, caspase activation, FAS S-glutathionylation, and total protein S-glutathionylation. GSTP activity is significantly reduced four hours after the administration of 50 mg/kg TLK117, and it stays reduced by roughly 60% for at least twenty-four hours[2].
References	[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]. 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.
Additional Infomation	See also: ... View More ...

Solubility Data

Solubility (In Vitro)

DMSO: 150 mg/mL (316.76 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (5.28 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (5.28 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 3: ≥ 2.5 mg/mL (5.28 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.1118 mL	10.5588 mL	21.1175 mL
	5 mM	0.4224 mL	2.1118 mL	4.2235 mL
	10 mM	0.2112 mL	1.0559 mL	2.1118 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.