Tacrolimus-FK506-DataSheet-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemETacrolimusCat. No.: HY-13756CAS No.: 104987-11-3Synonyms: FK506; Fujimycin; FR900506分式: CHNO分量: 804.02作靶點: Phosphatase; FKBP; Autophagy作通路: Metabolic Enzyme/Protease; Apoptosis; Autophagy;Immunology/Inflammation儲存式: 4C, protect

2、from light* 該產(chǎn)品在溶液狀態(tài)不穩(wěn)定，建議您現(xiàn)現(xiàn)配，即刻使。溶解性數(shù)據(jù)體外實驗 DMSO : 28 mg/mL (34.83 mM)H2O : 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (3.11 mM); Clear solution2. 請依序添加每種溶劑： 10% DMSO 90% (20% SBE-CD in saline)1/3 Master of Small Molecules 您邊的抑制劑師www.MedChemESolubility: 2.5 mg/mL (3.11 mM); Suspended so

3、lution; Need ultrasonic3. 請依序添加每種溶劑： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (3.11 mM); Clear solutionBIOLOGICAL ACTIVITY物活性 Tacrolimus (FK506; Fujimycin)種具有強效免疫抑制特性的環(huán)內(nèi)酯。 他克 司與FK506結(jié)合蛋 (FKBP)結(jié)合形成復(fù)合物并抑制鈣調(diào)神經(jīng)磷酸酶 (calcineurin phosphatase)。IC50 & Target PP2B (calcineurin phosphatase) 1Autophagy induce

4、r 2體外研究 Tacrolimus (FK506) inhibits calcium-dependent events, such as IL-2 gene transcription, NO synthaseactivation, cell degranulation, and apoptosis. Tacrolimus also potentiates the actions of glucocorticoids andprogesterone by binding to FKBPs contained within the hormone receptor complex, preve

5、nting degradation.The agent may enhance expression of the TGF-1 gene in a fashion analogous to that demonstrated forCsA. T cell proliferation in response to ligation of the T cell receptor is inhibited by Tacrolimus 1. Treatmentwith a low concentration of Tacrolimus (FK506,10 g/L) does not significa

6、ntly affect the proliferation ofMH3924A cells (P=0.135). Upon treatment with higher concentrations of Tacrolimus (100-1,000 g/L), theproliferation of MH3924A cells is significantly enhanced (P0.05). However, when different concentrations ofAMD3100 are combined with 100 g/L Tacrolimus, the in vitro p

7、roliferation of MH3924A cells is increased (P3.體內(nèi)研究 The therapeutic effect of Tacrolimus is investigated on progression and perpetuation of colitis byadministering Tacrolimus to Dextran sulfate sodium (DSS)-treated mice from Days 10 to 16 or to 23. At Days17 and 24, colon length is significantly sho

8、rtened, and colon weight is significantly higher in DSS-treatedcontrol animals than in normal animals. In addition, colon weight per unit length in the control group is morethan twice that in the normal group. While both 7 and 14 d treatment with Tacrolimus significantly suppressesincreases in colon

9、 weight per unit length in DSS-treated animals compared with the control group, thistreatment does not actually restore the colon shortening. In addition, this inhibitory effect of Tacrolimus onincreases in colon weight per unit length is more pronounced with 14-d than 7-d treatment, as shown by the

10、inhibitory percentages (59% vs. 28%) 4.PROTOCOLCell Assay 3 Tumor cell proliferation is determined by the MTT assay. Briefly, after MH3924A cells have reached thelogarithmic growth phase, a 0.2-mL cell suspension at 1104 cells/mL is added into each well of a 96-wellplate and cultured in DMEM for 24

11、h. When adherent growth is established, different concentrations ofTacrolimus (10, 100 and 1,000 g/L) , AMD3100 (10, 50 and 100 g/L) and Tacrolimus (0 and 100 g/L)+AMD3100 (0, 10, 50 and 100 g/L) are added into the plates. Untreated cells cultured in medium aloneare used as controls. After culturing

12、 for 48 h, 10 L MTT (5 g/L) are added, and each well is incubated for 6h; next, 150 L/well DMSO are added, followed by measurements of the absorbance at 570 mm on a2/3 Master of Small Molecules 您邊的抑制劑師www.MedChemEspectrophotometer reader. Each well is measured three times, and each sample is assayed

13、 in triplicate 3.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Mice 4Administration 4 Six-week-old male C57BL/6J mice are maintained in a temperature- and humidity-controlled room with a 12-h light-dark cycle. For the multiple dosing study, col

14、itic mice (n=10) are orally administered Tacrolimus at 30mg/kg for 7 d (Days 10 to 16) or 14 d (Days 10 to 23). Control (n=10) and normal groups (n=5) areadministered placebo using the same regimen. Tacrolimus or placebo is administered at 10 mL/kg. Mice areeuthanized by CO2 inhalation on the day fo

15、llowing the final dosing. For the single dosing study, colitic miceare orally administered Tacrolimus at 30 mg/kg or placebo (n=8) once on Day 7, 10, 17, or 24. Normal mice(n=4) are administered placebo using the same regimen. Mice are euthanized by CO2 inhalation eight hoursafter dosing 4.MCE has n

16、ot independently confirmed the accuracy of these methods. They are for reference only.戶使本產(chǎn)品發(fā)表的科研獻(xiàn) Nano Lett. 2019 Jan 9;19(1):124-134. Cell Syst. 2018 Apr 25;6(4):424-443.e7. Nano Res. 30 June 2018. Theranostics. 2018 Jan 1;8(4):878-893. J Cell Sci. 2019 Apr 26. pii: jcs.227777.See more customer val

17、idations on HYPERLINK / www.MedChemEREFERENCES1. Thomson AW, et al. Mode of action of Tacrolimus (FK506): molecular and cellular mechanisms. Ther Drug Monit. 1995 Dec;17(6):584-91.2. Vogel KR, et al. mTOR inhibitors rescue premature lethality and attenuate dysregulation of GABAergic/glutamatergic tr

18、anscription inmurine succinate semialdehyde dehydrogenase deficiency (SSADHD), a disorder of GABA metabolism. J Inherit Metab Dis. 2016Nov;39(6):877-886.3. Zhu H, et al. Tacrolimus promotes hepatocellular carcinoma and enhances CXCR4/SDF 1 expression in vivo. Mol Med Rep. 2014Aug;10(2):585-92.4. Okada Y, et al. Tacrolimus ameliorates dextran sulfate sodium-induced colitis in mice: implication of interleukin-1 suppression. BiolPharm Bull. 2011;34(12):1823-7.5. Yuwei He, et al. Drug targeting through platelet membrane-co