FK-506 (also Tacrolimus or fujimycin) is a potent calcineurin (protein phosphatase 2B) inhibitor that requires FK 506-binding protein 12 (FKBP12) for activity (IC50 = 3 nM). FK-506 inhibits secretion of IL-1, IL-2 (IC50 = 1 nM), IL-3, IL-4, IL-6 (IC50 = 35 nM), GM-CSF, TNFα (IC50 = 10 nM), IFNγ and Myc from activated T-cells in vitro. FK-506 exhibits potent immunosuppressive, neuroprotective and anticonvulsant activity in vivo. The physiological effects of FK-506 also include regulation of nitric oxide neurotoxicity, neurotransmitter release, and regulation of Ca2+ release via the ryanodine and inositol-(1,4,5)-trisphosphate (IP3) receptors. Furthermore, it has become clear that, predominantly as a result of CaN inhibition, FK506 alters multiple biochemical processes in a variety of cells besides lymphocytes. FK506 and ascomycin inhibit signaling pathways in astrocytes and change the pattern of cytokine and neurotrophin gene expression.
*The compound is unstable in solutions, freshly prepared is recommended
Neural Plast. 2022 Feb 7;2022:2900875.
Presynaptic NMDA Receptors Influence Ca2+ Dynamics by Interacting with Voltage-Dependent Calcium Channels during the Induction of Long-Term Depression
Tacrolimus (FK506) purchased from AbMole
BMC Biol. 2021 May 20;19(1):108.
Very long intergenic non-coding (vlinc) RNAs directly regulate multiple genes in cis and trans
Tacrolimus (FK506) purchased from AbMole
_J-Neurosci_2015-Jan-7.jpg)
J Neurosci. 2015 Jan 7;35(1):64-73.
Sleep slow wave-related homo and heterosynaptic LTD of intrathalamic GABAAergic synapses: involvement of T-type Ca2+ channels and metabotropic glutamate receptors.
Tacrolimus (FK506) purchased from AbMole
 |
Source | Univerrsite Pierre et Marie Curi (2015). Figure 4. FK-506 (Abmole Bioscience) |
| Method | Electrophysiology | |
| Cell Lines | whole-cell | |
| Concentrations | 50 μM | |
| Incubation Time | 1 h | |
| Results | As shown in figure 4D, no plasticity could be induced in the 8 neurons challenged by the induction protocol in this condition (post-protocol IPSCs amplitude: 99 ± 11% of baseline, p>0.05). |
.jpg) |
Source | The Journal of Neuroscience (2015). Figure 4.FK-506 from AbMole. |
| Method | Electrophysiology patch-clamp technique | |
| Cell Lines | neuron | |
| Concentrations | incubated for 1 h in FK-506 (at 25 and 50 µM) and then perfused with 20 µM FK-506. | |
| Incubation Time | 1 h | |
| Results | "No plasticity could be induced in the eight neurons challenged by the induction protocol in this condition (postprotocol IPSC amplitude: 99 ± 4% of baseline, p>0.05)." |
|
Source | The Journal of Neuroscience (2015). Figure 4.FK-506 from AbMole. |
| Method | Electrophysiology patch-clamp technique | |
| Cell Lines | neuron | |
| Concentrations | incubated for 1 h in FK-506 (at 25 and 50 µM) and then perfused with 20 µM FK-506. | |
| Incubation Time | 1 h | |
| Results | "No plasticity could be induced in the eight neurons challenged by the induction protocol in this condition (postprotocol IPSC amplitude: 99 ± 4% of baseline, p>0.05)." |
| Cell Experiment | |
|---|---|
| Cell lines | PMoH |
| Preparation method | PMoH (2.5 x 105 cells/well) were seeded in 12-well plates and treated with various concentrations of the immunosuppressants. At 24, 48 and 72 hr post-treatment, wells were washed twice with sterile PBS and cells were fixed and stained with 0.1% crystal violet in 1M citric acid containing 20% methanol for 20 minutes at room temperature. Wells were washed thoroughly with sterile PBS to remove excess crystal violet and then air-dried. Bound dye was solubilized with 100 μl 100% DMSO for 20 minutes and the absorbance of the supernatants was measured at 544 nm using the FluoStar Optima (BMG LabTech) plate reader. |
| Concentrations | 0.005 µg/ml |
| Incubation time | 24, 48, 72 h |
| Animal Experiment | |
|---|---|
| Animal models | BDF1 mice |
| Formulation | Solubilized in DMSO and diluted with PBS containing 10% dimethylacetamide (Sigma-Aldrich) and 6% Solutol (Sigma-Aldrich). |
| Dosages | twice daily at 3.2, 10, 32 or 100 mg/kg for 5 days |
| Administration | oral gavage |
| Molecular Weight | 804.02 |
| Formula | C44H69NO12 |
| CAS Number | 104987-11-3 |
| Solubility (25°C) | DMSO 90 mg/mL Ethanol 80 mg/mL |
| Storage | 2-8°C, protect from light |
| Species | Mouse | Rat | Rabbit | Guinea pig | Hamster | Dog |
| Weight (kg) | 0.02 | 0.15 | 1.8 | 0.4 | 0.08 | 10 |
| Body Surface Area (m2) | 0.007 | 0.025 | 0.15 | 0.05 | 0.02 | 0.5 |
| Km factor | 3 | 6 | 12 | 8 | 5 | 20 |
| Animal A (mg/kg) = Animal B (mg/kg) multiplied by | Animal B Km |
| Animal A Km |
For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.
[4] Dumont FJ. Curr Med Chem. FK506, an immunosuppressant targeting calcineurin function.
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