1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemETLK117Cat. No.: HY-13634BCAS No.: 152684-53-2Synonyms: TER117分式: CHNOS分量: 473.54作靶點(diǎn): Gutathione S-transferase作通路: Metabolic Enzyme/Protease儲(chǔ)存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性數(shù)據(jù)體外實(shí)驗(yàn) DMSO : 15

2、0 mg/mL (316.76 mM; Need ultrasonic)Mass Solvent1 mg 5 mg 10 mg Concentration制備儲(chǔ)備液1 mM 2.1118 mL 10.5588 mL 21.1175 mL5 mM 0.4224 mL 2.1118 mL 4.2235 mL10 mM 0.2112 mL 1.0559 mL 2.1118 mL請(qǐng)根據(jù)產(chǎn)品在不同溶劑中的溶解度，選擇合適的溶劑配制儲(chǔ)備液，并請(qǐng)注意儲(chǔ)備液的保存式和期限。體內(nèi)實(shí)驗(yàn)請(qǐng)根據(jù)您的實(shí)驗(yàn)動(dòng)物和給藥式選擇適當(dāng)?shù)娜芙獍?，配制前?qǐng)先配制澄清的儲(chǔ)備液，再依次添加助溶劑(為保證實(shí)驗(yàn)結(jié)果的可靠性，體內(nèi)實(shí)驗(yàn)的作液，

3、建議您現(xiàn)現(xiàn)配，當(dāng)天使；澄清的儲(chǔ)備液可以根據(jù)儲(chǔ)存條件，適當(dāng)保存；以下溶劑前的百分 指該溶劑在您配制終溶液中的體積占)：1. 請(qǐng)依序添加每種溶劑： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (5.28 mM); Clear solution2. 請(qǐng)依序添加每種溶劑： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.5 mg/mL (5.28 mM); Clear solution3. 請(qǐng)依序添加每種溶劑： 10% DMSO 90% corn oil1/3 Mast

4、er of Small Molecules 您邊的抑制劑師www.MedChemESolubility: 2.5 mg/mL (5.28 mM); Clear solutionBIOLOGICAL ACTIVITY物活性 TLK197TLK199的活性代謝物，選擇性抑制胱肽S-轉(zhuǎn)移酶P1-1 (Glutathione S-transferase P11(GSTP1-1)，結(jié)合 GSTP的 Ki 值為0.4 M。 TLK117還競(jìng)爭(zhēng)性地抑制醛酶I (glyoxalase I)， Ki值為0.56 M。IC50 & Target Ki: 0.4 M 1, 0.56 M (glyoxalase I)

5、 2體外研究 TLK117 is the most specific GSTP inhibitor to date, with a binding affinity greater than GSH itself and aselectivity for GSTP over 50-fold greater than the GSTM and GSTA classes (Ki=0.4 M) 1. TER 117 isdeveloped as a GST P1-1 isoenzyme inhibitor to circumvent the indicated contribution of GST

6、 P1-1 to drugresistance of tumor cells. To facilitate the cellular uptake of TER 117, it is delivered as a diethyl ester (TER117 DEE, also called TER 199). TER 117 is found to be a competitive inhibitor of both GST P1-1 andglyoxalase I 2.體內(nèi)研究 Oropharyngeal administration of the GSTP inhibitor, TLK11

7、7, at a time when fibrosis is already apparent,attenuated bleomycin- and AdTGF-induced remodeling, -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

8、 about 60% for at least 24 hours 2.PROTOCOLKinase Assay 2 The potency of TER 117 in the inhibition of GST P1-1/Ile-105 and GST P1-1/Val-105 is determined by meansof GSH competition experiments using 1 M TER 117 and three different fixed concentrations of GSH: 0.2,0.6, and 2.0 mM. The concentration o

9、f the second substrate, 1-chloro-2,4-dinitrobenzene (CDNB) rangedbetween 0.15 and 1.8 mM. In addition, the inhibitor is tested at different concentrations, 0 to 8 M, at a CDNBconcentration of 1 mM and the above GSH concentrations. Initial velocities are determinedspectrophotometrically at 30C. The c

10、onjugation reaction between GSH and CDNB is monitored at 340 nm in1 mL of 0.1 M sodium phosphate, pH 7.0 2.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Mice 1Administration 1 TLK117 is administered oropharyngeally at a dose of 50 mg/kg in a 0.

11、375 M Tris-HCl solution, pH =7.4, with0.02% DMSO. This Tris-HCl/DMSO solution is used as a vehicle control. Treatments are performed onceevery 3 days from day 14 to day 26 in both bleomycin and AdTGF modelsMCE has not independently confirmed the accuracy of these methods. They are for reference only

12、.REFERENCES1. The human glutathione transferase P1-1 specific inhibitor TER 117 designed for overcomingcytostatic-drug resistance is also a strong2/3 Master of Small Molecules 您邊的抑制劑師www.MedChemEinhibitor 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 . JCI Insight. 2016Jun 2;1(8). pii: e85717.McePdfHeightCau