Tacrolimus (FK506)
Tacrolimus (FK506, CAS 104987-11-3) is a potent, selective T-lymphocyte inhibitor and a macrolide immunosuppressant, and also an inhibitor of calcineurin[1].
In vitro, tacrolimus (FK506) inhibits the production of interleukin-2 (IL-2) and the response of mixed lymphocyte cultures. Addition of tacrolimus (FK506) to cell cultures also inhibits the reactivity of mouse or human mixed lymphocytes and the generation of cytotoxic T cells. Moreover, tacrolimus (FK506) dose-dependently inhibits the production of various cytokines induced by different stimuli, including IL-2, IL-3, IL-4, and gamma interferon. In animal transplant models, tacrolimus effectively prevents transplant rejection. In experimental liver transplantation, tacrolimus shows remarkable efficacy and hepatotropism[1].
Mechanistically, tacrolimus forms a complex with the FKBP12 protein, binds to and inhibits the phosphatase activity of calcineurin, and thereby blocks the transcription and secretion of cytokines such as IL-2, IL-3, IL-4, and gamma interferon. In cellular experiments, it inhibits IL-2 secretion with an IC50 range of 0.1-1 nM[1].
References: [1] Wallemacq PE1, Reding R. FK506 (tacrolimus), a novel immunosuppressant in organ transplantation: clinical, biomedical, and analytical aspects. Clin Chem. 1993 Nov; 39(11 Pt 1):2219-28.
- 1. Tao Liao, Xiaoyi Shi, et al. "Targeted Tacrolimus Delivery via Manganese Dioxide Nanoparticles for Mitigating Acute Allograft Rejection in Murine Cardiac Transplantation." Biomaterials. 2025 Oct 3:327:123762. PMID: 41056839
- 2. Qin Wang, Xuedan Nie, et al. "Redox nanodrugs alleviate chronic kidney disease by reducing inflammation and regulating ROS." Biomater. Sci., 2024, 12, 6403-6415. PMID: 39526526
- 3. Seyed Mojtaba Hosseini, Shiva Nemati, et al. "Astrocytes originated from neural stem cells drive the regenerative remodeling of pathologic CSPGs in spinal cord injury." Stem Cell Reports. 2024 Oct 8;19(10):1451-1473. PMID: 39303705
- 4. Wenlun Wang, Lisheng Yu, et al. "NFAT3-FasL axis synchronously regulates apoptosis and necroptosis in murine cochlear outer hair cells after noise trauma." Front Mol Neurosci. 2024 Jul 15:17:1422646. PMID: 39077755
- 5. Eun-Ji Choi, Hyun-Taek Oh, et al. "Metabolic stress induces a double-positive feedback loop between AMPK and SQSTM1/p62 conferring dual activation of AMPK and NFE2L2/NRF2 to synergize antioxidant defense." Autophagy. 2024 Nov;20(11):2490-2510. PMID: 38953310
- 6. PENGYU JIA, NAN WU, et al. "Different roles of BAG3 in cardiac physiological hypertrophy and pathological remodeling." Transl Res. 2021 Jul;233:47-61 PMID: 33578031
- 7. Carsten Deppermann, Moritz Peiseler, et al. "Tacrolimus impairs Kupffer cell capacity to control bacteremia: why transplant recipients are susceptible to infection." Hepatology. 2020 Aug 6 PMID: 32761929
- 8. Souvik Dey, Alaa Eisa, et al. "Roles of glycogen synthase kinase 3 alpha and calcineurin in regulating the ability of sperm to fertilize eggs." FASEB J. 2020;34(1):1247–1269 PMID: 31914663
- 9. Peiffer BJ, Qi L, et al. "Activation of BMP Signaling by FKBP12 Ligands Synergizes with Inhibition of CXCR4 to Accelerate Wound Healing." Cell Chem Biol. 2019 May 16;26(5):652-661.e4 PMID: 30827938
- 10. Wang Z, Wang Y, et al. "Transient receptor potential channel 1/4 reduces subarachnoid hemorrhage-induced early brain injury in rats via calcineurin-mediated NMDAR and NFAT dephosphorylation." Sci Rep. 2016 Sep 19;6:33577 PMID: 27641617
| Physical Appearance | A solid |
| Storage | Store at -20°C |
| M.Wt | 804.02 |
| Cas No. | 104987-11-3 |
| Formula | C44H69NO12 |
| Synonyms | Tacrolimus |
| Solubility | ≥26.6 mg/mL in DMSO; insoluble in H2O; ≥84.5 mg/mL in EtOH |
| 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 |
| Canonical SMILES | O=C([C@@](CCCC1)([H])N1C(C([C@@]2(O)[C@H](C)C[C@H](OC)[C@@](O2)([H])[C@@H](OC)C[C@@H](C)C/C(C)=C/[C@H]3CC=C)=O)=O)O[C@H](/C(C)=C/[C@H]4C[C@@H](OC)[C@H](O)CC4)[C@H](C)[C@@H](O)CC3=O |
| Shipping Condition | Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice. |
| General tips | We do not recommend long-term storage for the solution, please use it up soon. |
| Cell experiment: | |
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Cell lines |
Liver slices, human lung fibroblasts |
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Preparation method |
The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
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Reacting condition |
2 μM and 4 μM for 3 days |
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Applications |
FK506 reduced type I collagen synthesis in liver slices cultured in vitro [1]. Moreover, FK506 (2 μM) decreased the type I collagen protein synthesis without affecting expression of collagen mRNAs [2]. |
| Animal experiment: | |
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Animal models |
Rats model |
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Dosage form |
4 mg/kg; i.p. injections, daily dose for 4 weeks; or 1, 2 and 3 mg/kg, p.o. for 10 consecutive days |
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Applications |
FK506 (4 mg/kg) prevented early stages of ethanol induced hepatic fibrosis by targeting LARP6 dependent mechanism of collagen synthesis in rats [1]. Moreover, FK506 (2 and 3 mg/kg) treatment resulted in attenuation of arterial ischemic reperfusion (I/R) induced axonal degeneration and histopathological alterations in rats [2]. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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References: 1Manojlovic, Z., Blackmon, J. and Stefanovic, B. (2013) Tacrolimus (FK506) prevents early stages of ethanol induced hepatic fibrosis by targeting LARP6 dependent mechanism of collagen synthesis. PLoS One. 8, e65897 2Muthuraman, A. and Sood, S. (2010) Pharmacological evaluation of tacrolimus (FK-506) on ischemia reperfusion induced vasculatic neuropathic pain in rats. J Brachial Plex Peripher Nerve Inj. 5, 13 |
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| Description | FK-506, a 23-membered macrolide lactone, is an inhibitor of peptidyl-prolyl isomerase. | |||||
| Targets | peptidyl-prolyl isomerase | |||||
| IC50 | ||||||
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