1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEGSK2837808ACat. No.: HY-100681CAS No.: 1445879-21-9分式: CHFNOS分量: 649.62作靶點: Lactate Dehydrogenase作通路: Metabolic Enzyme/Protease儲存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性數據體外實驗 DMSO : 100 mg/mL (153

2、.94 mM)H2O : 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (3.85 mM); Clear solution2. 請依序添加每種溶劑： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.5 mg/mL (3.85 mM); Suspended solution; Need ultrasonic1/3 Master of Small Molecules 您邊的抑制劑師www.MedChemE3. 請依序添加每種溶劑： 10% DMSO 90% corn oilSolubi

3、lity: 2.5 mg/mL (3.85 mM); Clear solutionBIOLOGICAL ACTIVITY物活性 GSK2837808A是有效和選擇性的乳酸脫氫酶A (LDHA) 抑制劑，對LDHA 和 LDHB的 IC50 值分別為1.9 和14nM。IC50 & Target IC50: 1.9 nM (LDHA), 1.9 nM (LDHB) 1體外研究 GSK2837808A rapidly and profoundly inhibits lactate production rates in multiple cancer cell lines includinghep

4、atocellular and breast carcinomas. The potency of GSK2837808A across 30 cancer cell lines withdifferent LDHA and LDHB expression levels ranges from 400 nM to no effect (EC50 reported as 30 M).GSK2837808A potency does not correlate with LDHA, LDHB, or the total LDH expression levels.GSK2837808A inhib

5、its lactate production in hypoxia but at higher concentrations than in normoxia (EC50=10M). It also reduces ECAR with EC50=10 M. LDH inhibition by GSK2837808A alters multiple metabolicpathways in Snu398 cells 1.體內研究 Clearance following IV infusion of GSK2837808A at 0.25 mg/kg is shown to be 69 mL/mi

6、nute/kg in rats,which exceeds the animal liver blood flow. Oral dosing of GSK2837808A at 50 mg/kg in rats or 100 mg/kg inmice results in blood compound levels at or below the detection limit of 2.5 ng/mL 1.PROTOCOLCell Assay 1 Sixty thousand Snu398 cells per well are plated in 6-well tissue culture

7、plates in RPMI-1640 mediumsupplemented with 2.5% charcoal-stripped FBS. Cells are allowed to attach overnight and then DMSOcontrol or the indicated doses of LDHA inhibitor dissolved in DMSO are added directly to the wells. After 4 to8 days of incubation in the indicated oxygen conditions, adherent c

8、ells are trypsinized, counted, and had theirviability assessed by the trypan-blue exclusion method using the Vi-Cell XR Cell Viability Analyzer 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Mice: GSK2837808A is administered to male CD mice or

9、 male Sprague-Dawley rats orally or by intravenousAdministration 1 (IV) infusion over 120 minutes into a femoral vein. Arterial blood samples are collected over time andGSK2837808A concentration is determined by liquid chromatography (LC)/MS/MS analysis 1.MCE has not independently confirmed the accu

10、racy of these methods. They are for reference only.戶使本產品發表的科研獻 Nat Commun. 2019 Jun 20;10(1):2701. Cell Mol Life Sci. 2019 Apr;76(8):1579-1593.See more customer validations on HYPERLINK / www.MedChemE2/3 Master of Small Molecules 您邊的抑制劑師www.MedChemEREFERENCES1. Billiard J, et al. Quinoline 3-sulfonamides inhibit lactate dehydrogenase A and reverse aerobic glycolysis in cancer cells. Cancer Metab.2013 Sep 6;1(1):19.McePdfHeightCaution: Product has not been full