他克莫司作用機(jī)制 - Medchemexpress - MCE中國(guó)

1、Product Data SheetTacrolimusCat. No.: HY-13756CAS No.: 104987-11-3分式: CHNO分量: 804.02作靶點(diǎn): Phosphatase; FKBP; Bacterial; Autophagy作通路: Metabolic Enzyme/Protease; Apoptosis; Autophagy; Immunology/Inflammation;Anti-infection儲(chǔ)存式: 4C, protect 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(shí)驗(yàn) DMSO : 28 mg/mL (3

2、4.83 mM)H2O : 0.1 mg/mL (insoluble)* means soluble, but saturation unknown.SolventMass1 mg 5 mg 10 mgConcentration制備儲(chǔ)備液1 mM 1.2438 mL 6.2188 mL 12.4375 mL5 mM 0.2488 mL 1.2438 mL 2.4875 mL10 mM 0.1244 mL 0.6219 mL 1.2438 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；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.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?/p>

3、。以下溶解案都請(qǐng)先按照 In Vitro 式配制澄清的儲(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，澄 的儲(chǔ)備液可以根據(jù)儲(chǔ)存條件，適當(dāng)保存；體內(nèi)實(shí)驗(yàn)的作液，建議您現(xiàn)現(xiàn)配，當(dāng)天使； 以下溶劑前顯的百分 指該溶劑在您配制終溶液中的體積占；如在配制過程中出現(xiàn)沉淀、析出現(xiàn)象，可以通過加熱和/或超聲的式助溶1. 請(qǐng)依序添加每種溶劑： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (3.11 mM); Clear solution此案可獲得 2.5 mg/mL (3.11 mM，飽和度未知) 的澄清溶液。以 1 mL 作

4、液為例，取 100 L 25.0 mg/mL 的澄 DMSO 儲(chǔ)備液加到 400 L PEG300 中，混合均勻；向上述體系中加50 L Tween-80，混合均勻；然后繼續(xù)加 450 L 理鹽定容 1 mL。2. 請(qǐng)依序添加每種溶劑： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.5 mg/mL (3.11 mM); Suspended solution; Need ultrasonic此案可獲得 2.5 mg/mL (3.11 mM) 的均勻懸濁液，懸濁液可于服和腹腔注射。Page 1 of 2 www.MedChemE以 1 mL 作液

5、為例，取 100 L 25.0 mg/mL 的澄均勻。DMSO 儲(chǔ)備液加到 900 L 20% 的 SBE-CD 理鹽溶液中，混合3. 請(qǐng)依序添加每種溶劑： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (3.11 mM); Clear solution此案可獲得 2.5 mg/mL (3.11 mM，飽和度未知) 的澄 溶液，此案不適于實(shí)驗(yàn)周 期在半個(gè)以上的實(shí)驗(yàn)。以 1 mL 作液為例，取 100 L 25.0 mg/mL 的澄 DMSO 儲(chǔ)備液加到 900 L 油中，混合均勻。BIOLOGICAL ACTIVITY物活性 Tacrolimus (FK

6、506)，環(huán)內(nèi)酯類，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)，從抑制 T 淋巴細(xì)胞信號(hào)轉(zhuǎn)導(dǎo)和 IL-2 轉(zhuǎn)錄。具有強(qiáng)免疫抑制特性。IC & Target PP2B (calcineurin phosphatase)1Autophagy inducer2體外研究 Tacrolimus (FK506) inhibits calcium-dependent events, such as IL-2 gene transcription, NO synthase activation, celldegranulatio

7、n, and apoptosis. Tacrolimus also potentiates the actions of glucocorticoids and progesterone by bindingto FKBPs contained within the hormone receptor complex, preventing degradation. The agent may enhanceexpression of the TGF-1 gene in a fashion analogous to that demonstrated for CsA. T cell prolif

8、eration in response toligation of the T cell receptor is inhibited by Tacrolimus1. Treatment with a low concentration of Tacrolimus(FK506,10 g/L) does not significantly affect the proliferation of MH3924A cells (P=0.135). Upon treatment withhigher concentrations of Tacrolimus (100-1,000 g/L), the pr

9、oliferation of MH3924A cells is significantly enhanced(P0.05). However, when different concentrations of AMD3100 are combined with 100 g/L Tacrolimus,the in vitro proliferation of MH3924A cells is increased (P0.01)3.體內(nèi)研究 The therapeutic effect of Tacrolimus is investigated on progression and perpetu

10、ation of colitis by administeringTacrolimus to Dextran sulfate sodium (DSS)-treated mice from Days 10 to 16 or to 23. At Days 17 and 24, colon length is significantly shortened, and colon weight is significantly higher in DSS-treated control animals than innormal animals. In addition, colon weight p

11、er unit length in the control group is more than twice that in the normalgroup. While both 7 and 14 d treatment with Tacrolimus significantly suppresses increases in colon weight per unitlength in DSS-treated animals compared with the control group, this treatment does not actually restore the colon

12、shortening. In addition, this inhibitory effect of Tacrolimus on increases in colon weight per unit length is morepronounced with 14-d than 7-d treatment, as shown by the inhibitory percentages (59% vs. 28%)4.PROTOCOLCell Assay 3 Tumor cell proliferation is determined by the MTT assay. Briefly, afte

13、r MH3924A cells have reached the logarithmicgrowth phase, a 0.2-mL cell suspension at 1104 cells/mL is added into each well of a 96-well plate and cultured inDMEM for 24 h. When adherent growth is established, different concentrations of Tacrolimus (10, 100 and 1,000 g/L) , AMD3100 (10, 50 and 100 g

14、/L) and Tacrolimus (0 and 100 g/L)+AMD3100 (0, 10, 50 and 100 g/L) areadded into the plates. Untreated cells cultured in medium alone are used as controls. After culturing for 48 h, 10 LMTT (5 g/L) are added, and each well is incubated for 6 h; next, 150 L/well DMSO are added, followed bymeasurement

15、s of the absorbance at 570 mm on a spectrophotometer reader. Each well is measured three times, andeach sample is assayed in triplicate3.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Page 2 of 3 www.MedChemEAnimal Mice4Administration 4 Six-week-old ma

16、le C57BL/6J mice are maintained in a temperature- and humidity-controlled room with a 12-h light- dark cycle. For the multiple dosing study, colitic mice (n=10) are orally administered Tacrolimus at 30 mg/kg for 7 d(Days 10 to 16) or 14 d (Days 10 to 23). Control (n=10) and normal groups (n=5) are a

17、dministered placebo using thesame regimen. Tacrolimus or placebo is administered at 10 mL/kg. Mice are euthanized by CO2 inhalation on the dayfollowing the final dosing. For the single dosing study, colitic mice are orally administered Tacrolimus at 30 mg/kg orplacebo (n=8) once on Day 7, 10, 17, or

18、 24. Normal mice (n=4) are administered placebo using the same regimen.Mice are euthanized by CO2 inhalation eight hours after dosing4.MCE has not 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. J Extracell Vesicles.

19、 2019 Dec. Cell Syst. 2018 Apr 25;6(4):424-443.e7. Nano Res. 30 June 2018. Theranostics. 2018 Jan 1;8(4):878-893.See more customer validations on HYPERLINK www.MedChemE www.MedChemEREFERENCES1. Thomson AW, et al. Mode of action of Tacrolimus (FK506): molecular and cellular mechanisms. Ther Drug Moni

20、t. 1995 Dec;17(6):584-91.2. Vogel KR, et al. mTOR inhibitors rescue premature lethality and attenuate dysregulation of GABAergic/glutamatergic transcription in murine succinatesemialdehyde dehydrogenase deficiency (SSADHD), a disorder of GABA metabolism. J Inherit Metab Dis. 2016 Nov;39(6):877-886.3. Zhu H, et al. Tacro