Ko-143 - BCRP 抑制劑 - 生命科學(xué)試劑 - MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEKo 143Cat. No.: HY-10010CAS No.: 461054-93-3分式: CHNO分量: 469.57作靶點: BCRP作通路: Membrane Transporter/Ion Channel儲存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性數(shù)據(jù)體外實驗 DMSO : 50 mg/mL (106.48 mM)H2O : 40% PEG

2、300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (5.32 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 (5.32 mM); Suspended solution; Need ultrasonic and warming and heat to 50C1/3 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 o

3、ilSolubility: 2.5 mg/mL (5.32 mM); Clear solutionBIOLOGICAL ACTIVITY物活性 Ko 143是有效且選擇性的ATP結(jié)合盒亞家族G成員2 (ABCG2) 抑制劑。IC50 & Target EC90: 26 nM (BCRP)體外研究 Ko143 (10 nM) significantly decreases (2.5-fold) the IC50 of MTX for HEK G2 cells and mouse G2 cells.Ko143 (1-100 M) metabolite does not inhibit the fu

4、nction of ABC Transporters 1. Reversal of drugresistance in topotecan-selected mouse MEF3.8/T6400 cells and human IGROV1/T8 cells by FTC analogueKo143. Ko143 is applied at zero, one, or eight times the EC90 concentration of 25 nM 2. Ko143 inhibitsBCRP-mediated transport of rosuvastatin in Madin-Darb

5、y Canine Kidney (MDCK) 2-BCRP421CC (wild type)cells and MDCK2-BCRP421AA (mutant type) cells 3.體內(nèi)研究 Ko143 (10 mg/kg, p.o.) increases the oral availability of topotecan in mice 2. Ko143 significantly affects thepharmacokinetics of rosuvastatin in rats 3.PROTOCOLCell Assay 2 cells are plated at 400 or

6、1000/well in 96-well plates the night before addition of drugs. A concentration seriesof drug is applied along one plate axis and left for the duration of the assay. Plates are harvested after 4-5days while untreated wells are still subconfluent. Relative cell proliferation is quantified with CyQuan

7、t or SybrGreen I fluorescent nucleic acid stains. Assays with human cell lines are performed in the presence of 0.1 m PSC833 to inhibit confounding P-gp activity.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Oral toxicity of FTC analogues in mi

8、ce is tested by mixing 50 mg/mL stocks in DMSO 1:1 with Tween 80Administration 2 (polyoxyethylene sorbitan mono-oleate) and diluting with 5% w/v glucose such that the final volumeadministered by oral gavage is 10 L/g of body weight. Pairs of mice are administered oral doses of 50mg/kg Ko132, Ko134,

9、Ko143, or vehicle under light methoxyflurane anesthesia. Final tests of 50 mg/kgKo134 or Ko143 are performed on additional pairs of unanesthetized animals to observe any behavioraleffects. Further, another pair of mice receive the higher dose of 100 mg/kg Ko134. For i.p. toxicity tests, theFTC analo

10、gue stocks in DMSO are dispersed in at least 10 volumes of sterile corn oil such that the injectedvolume is 5 L/g of body weight. After pilot tests at lower doses show no adverse effects, mice (4 per group)are administered vehicle or 10 mg/kg i.p. of Ko132, Ko134, or Ko143. The mice are observed con

11、tinuouslyduring the first hour after administration and then at increasing intervals for 2 weeks, after which they aresacrificed for histological examination of major organs and structures including brain, salivary glands, heart,lungs, liver, adrenal glands, kidneys, urinary tract, spleen, thymus, b

12、one marrow, pancreas, stomach,intestines, cecum, colon, testes, epididymus, skin, head, trunk, and limbs.MCE has not independently confirmed the accuracy of these methods. They are for reference only.2/3 Master of Small Molecules 您邊的抑制劑師www.MedChemE戶使本產(chǎn)品發(fā)表的科研獻 Proc Natl Acad Sci U S A. 2019 Jun 10.

13、Arch Toxicol. 2018 Jun;92(6):2027-2042. Drug Deliv. 2017 Nov;24(1):1453-1459. Drug Metab Dispos. 2019 Mar 28. J Drug Target. 2016;24(5):441-9.See more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Weidner LD, et al. The Inhibitor Ko143 Is Not Specific for ABCG2. J Pharmacol Exp Ther.

14、2015 Sep;354(3):384-93.2. JD Allen et al. Potent and Specific Inhibition of the Breast Cancer Resistance Protein Multidrug Transporter in Vitro and in MouseIntestine by a Novel Analogue of Fumitremorgin C. Mol. Cancer Ther. 2002, 1, 417-425.3. Wen JH, et al. Effect of Ursolic Acid on Breast Cancer R

15、esistance Protein-mediated Transport of Rosuvastatin In Vivo and Vitro. ChinMed Sci J. 2015 Dec;30(4):218-25.4. Hou J, et al. Quantitative determination and pharmacokinetic study of the novel anti-Parkinsons disease candidate drug FLZ in rat brainby high performance liquid chromatography-tandem mass spectrometry. J Pharm Biomed Anal. 2012 Jul;66:232-9.5. Liu K, et al. Metabolism of KO143, an ABCG2 inhibitor. Drug Metab Pharmac