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10mg |
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50mg |
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100mg |
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250mg |
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500mg |
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1g |
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2g |
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Other Sizes |
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Purity: ≥98%
Tacrolimus (FK506, Fujimycin, FR-900506, Prograf), a natural macrocyclic lactone isolated from the fungus Streptomyces tsukubaensis, is an effective immunosuppressive drug that works in conjunction with other drugs to prevent organ transplant rejection (kidney, heart, liver). It works by attaching to the FK506 binding protein (FKBP) and inhibiting calcineurin phosphatase, which prevents the signaling of T lymphocytes and the transcription of IL-2. Tacrolimus can lower the risk of organ rejection by reducing the patient's immune system's activity. Additionally, atopic dermatitis (eczema), severe refractory uveitis following bone marrow transplants, exacerbations of minimal change disease, TH2-mediated illnesses like Kimura's disease, and the skin condition vitiligo are all treated with it topically.
Targets |
FKBP12; calcineurin
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ln Vitro |
FK-506 and cyclosporin A block translocation of the cytoplasmic component without affecting synthesis of the nuclear subunit in T lymphocytes.[1] K-506 inhibits a Ca(2+)-dependent process necessary for the induction of interleukin-2 transcription, which stops T-cell proliferation. [2] Cyclophilins and FK 506-binding proteins (FKBPs) are two different families of intracellular proteins (immunophilins) that FK 506 binds to. At drug concentrations that prevent activated T cells from producing interleukin 2, FK-506 specifically inhibits cellular calcineurin. [3] By blocking the same subset of early calcium-associated events involved in lymphokine expression, apoptosis, and degranulation, FK-506 and CsA have nearly identical biological effects on cells. The FK-506 binding proteins (FKBPs), a family of intracellular receptors, are where FK-506 binds. [4]
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ln Vivo |
FK-506 results in increase in the paw and tail withdrawal threshold as revealed by behavioral pain assessment in rats against hyperalgesic and allodynic stimuli. Additionally, FK-506 lowers serum nitrate and thiobarbituric acid reactive substance (TBARS) levels. It also lowers tissue myeloperoxidase (MPO) and total calcium levels, while raising tissue reduced glutathione levels in rats. In rats with ischemia reperfusion (I/R), FK-506 reduces the progression of neuronal edema and axonal degeneration. [5]
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Enzyme Assay |
Tacrolimus (FK506) inhibits calcium-dependent events, such as IL-2 gene transcription, NO synthase activation, cell degranulation, and apoptosis. Tacrolimus also potentiates the actions of glucocorticoids and progesterone by binding to FKBPs contained within the hormone receptor complex, preventing degradation. The agent may enhance expression of the TGFβ-1 gene in a fashion analogous to that demonstrated for CsA. T cell proliferation in response to ligation of the T cell receptor is inhibited by Tacrolimus. Treatment with a low concentration of Tacrolimus (FK506,10 μg/L) does not significantly affect the proliferation of MH3924A cells (P=0.135). Upon treatment with higher concentrations of Tacrolimus (100-1,000 μg/L), the proliferation of MH3924A cells is significantly enhanced (P<0.01). However, when different concentrations of AMD3100 are combined with 100 μg/L Tacrolimus, the in vitro proliferation of MH3924A cells is increased (P<0.01).
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Cell Assay |
Cells were cultured in the presence of 10 nM FK 506 for 1 hr and washed, and phosphatase activity was measured in lysates.
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Animal Protocol |
Mice; Six-week-old male C57BL/6J mice are maintained in a temperature- and humidity-controlled room with a 12-h light-dark cycle. FTacrolimus 30 mg/kg is given orally to colitic mice (n=10) for either 7 or 14 days (Days 10 to 23) as part of the multiple dosing study. The same regimen is used to administer placebos to the control group (n = 10) and the normal group (n = 5). 10 mL/kg of placebo or tacrolimus is given. On the day after the final dose, mice are put to death by CO2 inhalation. For the single-dose study, colitic mice are given Tacrolimus or a placebo (n=8) orally once on Days 7, 10, 17, or 24. The same procedure is used to administer a placebo to normal mice (n = 4). Eight hours after dosing, mice are put to death by CO2 inhalation.
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References |
Molecular Formula |
C44H69NO12
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Molecular Weight |
804.0182
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Exact Mass |
973.29551
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Elemental Analysis |
C, 57.92; H, 5.69; Cl, 3.64; F, 5.85; N, 7.19; O, 9.85; S, 9.87
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CAS # |
104987-11-3
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Related CAS # |
Tacrolimus monohydrate;109581-93-3;Tacrolimus-13C,d2;1356841-89-8
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Appearance |
Solid powder
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SMILES |
C[C@@H]1C[C@@H]([C@@H]2[C@H](C[C@H]([C@@](O2)(C(=O)C(=O)N3CCCC[C@H]3C(=O)O[C@@H]([C@@H]([C@H](CC(=O)[C@@H](/C=C(/C1)\C)CC=C)O)C)/C(=C/[C@@H]4CC[C@H]([C@@H](C4)OC)O)/C)O)C)OC)OC
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InChi Key |
QJJXYPPXXYFBGM-LFZNUXCKSA-N
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InChi Code |
InChI=1S/C44H69NO12/c1-10-13-31-19-25(2)18-26(3)20-37(54-8)40-38(55-9)22-28(5)44(52,57-40)41(49)42(50)45-17-12-11-14-32(45)43(51)56-39(29(6)34(47)24-35(31)48)27(4)21-30-15-16-33(46)36(23-30)53-7/h10,19,21,26,28-34,36-40,46-47,52H,1,11-18,20,22-24H2,2-9H3/b25-19+,27-21+/t26-,28+,29+,30-,31+,32-,33+,34-,36+,37-,38-,39+,40+,44+/m0/s1
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Chemical Name |
(1R,9S,12S,13R,14S,17R,18E,21S,23S,24R,25S,27R)-1,14-dihydroxy-12-[(E)-1-[(1R,3R,4R)-4-hydroxy-3-methoxycyclohexyl]prop-1-en-2-yl]-23,25-dimethoxy-13,19,21,27-tetramethyl-17-prop-2-enyl-11,28-dioxa-4-azatricyclo[22.3.1.04,9]octacos-18-ene-2,3,10,16-tetrone
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Synonyms |
FR900506;FR 900506; FR-900506; FK 506; FK-506; FK506; fujimycin; Prograf; Protopic; Advagraf; Astagraf XL
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HS Tariff Code |
2934.99.9001
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Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: This product requires protection from light (avoid light exposure) during transportation and storage. |
Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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Solubility (In Vitro) |
DMSO: ~94 mg/mL (~116.9 mM)
Water: <1 mg/mL Ethanol: ~83 mg/mL (~103.2 mM) |
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Solubility (In Vivo) |
Solubility in Formulation 1: 2.75 mg/mL (3.42 mM) in 5% DMSO + 40% PEG300 + 5% Tween80 + 50% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (3.11 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. View More
Solubility in Formulation 3: 2.5 mg/mL (3.11 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. Solubility in Formulation 4: ≥ 2.5 mg/mL (3.11 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL corn oil and mix evenly. Solubility in Formulation 5: 5% DMSO+corn oil: 15mg/mL |
Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
1 mM | 1.2438 mL | 6.2188 mL | 12.4375 mL | |
5 mM | 0.2488 mL | 1.2438 mL | 2.4875 mL | |
10 mM | 0.1244 mL | 0.6219 mL | 1.2438 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration: mg/mL;
Method for preparing DMSO stock solution: mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation::Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O,mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
NCT Number | Status | Interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
NCT04645667 | Recruiting | Drug: Tacrolimus | Acute GVHD | UNC Lineberger Comprehensive Cancer Center |
February 1, 2021 | |
NCT05744635 | Recruiting | Drug: Tacrolimus | Liver Failure | Chiesi Hungary Ltd. | May 10, 2023 | |
NCT03760263 | Recruiting | Drug: Tacrolimus | Transplant;Failure,Kidney | Sentara Norfolk General Hospital |
January 16, 2020 | Phase 4 |
NCT04380311 | Recruiting | Device: Tacrolimus Dosing Support Tool |
Heart Transplant Failure and Rejection |
University of Utah | May 1, 2020 | |
NCT03438773 | Recruiting | Drug: Envarsus Drug: Tacrolimus |
Kidney Transplant Failure and Rejection |
California Institute of Renal Research |
July 11, 2018 | Phase 1 |
Failure of the increase of autophagic flux. PLoS One. 2012; 7(8): e43418. td> |
Inhibition of starvation-induced autophagic flux by MHY1485. td> |
Activation of mTOR by MHY1485. td> |