WARNING: This product is for research use only, not for human or veterinary use.
Hodoodo CAT#: H100795
CAS#: 104987-11-3 (anhydrous)
Description: Tacrolimus, also known as FK-506, is an immunosuppressive drug used mainly after allogeneic organ transplant to reduce the activity of the patient's immune system and to lower the risk of organ rejection. It is also used in a topical preparation in the treatment of atopic dermatitis (eczema), severe refractory uveitis after bone marrow transplants, exacerbations of minimal change disease, TH2-mediated diseases such as Kimura's disease, and the skin condition vitiligo. FK-506 is a macrolide isolated from the fungus Streptomyces tsukubaensis. Note: this product is replaced by tacrolimus hydrate (CAT#592996)
Hodoodo Cat#: H100795
Name: Tacrolimus anhydrous
CAS#: 104987-11-3 (anhydrous)
Chemical Formula: C44H69NO12
Exact Mass: 803.48
Molecular Weight: 804.020
Elemental Analysis: C, 65.73; H, 8.65; N, 1.74; O, 23.88
Related CAS #: 109581-93-3 (hydrate) 104987-11-3 (anhydrous)
Synonym: FK 506, FK-506, FK506, fujimycin, fujimycin, Prograf, Protopic, Advagraf; Astagraf XL;
IUPAC/Chemical Name: [3S [3R*[E(1S*,3S*,4S*)], 4S*,5R*,8S*,9E,12R*,14R*,15S*,16R*,18S*,19S*,26aR*]] -5,6,8,11,12,13,14,15,16,17,18,19,24,25,26,26a-hexadecahydro-5,19-dihydroxy-3-[2-(4-hydroxy-3-methoxycyclohexyl)-1-methylethenyl]-14,16-dimethoxy-4,10,12,18-tetramethyl-8-(2-propenyl)-15,19-epoxy-3H-pyrido[2,1-c][1,4] oxaazacyclotricosine-1,7,20,21(4H,23H)-tetrone
InChi Key: QJJXYPPXXYFBGM-GANIDMSDSA-N
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
SMILES Code: 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]4CC(OC)C(O)CC4)[C@H](C)[C@@H](O)CC3=O
Appearance: White solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO, not in water
Shelf Life: >2 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
More Info:
| Biological target: | Forms a complex (Ki = 0.2 nM) with FK-506 binding protein 12 (FKBP12). |
| In vitro activity: | The effect of tacrolimus on endoplasmic reticulum stress-mediated osteoclastogenesis was evaluated using mouse bone marrow cells that were cultured with or without tacrolimus to induce osteoclast differentiation. In vitro, tacrolimus inhibited receptor activator of nuclear factor-κB ligand-mediated osteoclast formation. Furthermore, tacrolimus inhibited glucose-regulated protein (GRP78), protein kinase R-like endoplasmic reticulum kinase, inositol-requiring enzyme 1 (IRE 1), and activating transcription factor 6 (ATF6). Reference: Cell Biol Int. 2018 Apr;42(4):393-402. https://onlinelibrary.wiley.com/doi/abs/10.1002/cbin.10861 |
| In vivo activity: | A mouse model of arthritis was established by immunizing mice with bovine type II collagen. Tacrolimus was orally administered to mice from day 20 to 45 following the initial immunization, and histopathological changes and expression of specific biomarkers of endoplasmic reticulum stress-mediated inflammatory signaling pathways were examined. Tacrolimus significantly ameliorated osteolysis and endoplasmic reticulum stress intensity in mice. These findings suggest that tacrolimus exhibits an anti-inflammation effect in rheumatoid arthritis and might inhibit joint damage progression by inhibiting endoplasmic reticulum stress. Reference: Cell Biol Int. 2018 Apr;42(4):393-402. https://onlinelibrary.wiley.com/doi/abs/10.1002/cbin.10861 |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 87.6 | 108.95 | |
| DMF | 30.0 | 37.31 | |
| Ethanol | 70.1 | 87.22 | |
| Ethanol:PBS (pH 7.2) (1:5) | 0.2 | 0.19 |
The following data is based on the product molecular weight 804.02 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|---|---|---|
| 1 mM | 1.15 mL | 5.76 mL | 11.51 mL |
| 5 mM | 0.23 mL | 1.15 mL | 2.3 mL |
| 10 mM | 0.12 mL | 0.58 mL | 1.15 mL |
| 50 mM | 0.02 mL | 0.12 mL | 0.23 mL |
| Formulation protocol: | 1. Lee WS, Jeong JH, Lee EG, Choi Y, Kim JH, Kim HR, Yoo WH. Tacrolimus regulates endoplasmic reticulum stress-mediated osteoclastogenesis and inflammation: In vitro and collagen-induced arthritis mouse model. Cell Biol Int. 2018 Apr;42(4):393-402. doi: 10.1002/cbin.10861. Epub 2018 Jan 24. PMID: 28833755. 2. DU C, Wang X, Zhao L, Dai K. [In vitro effects of tacrolimus on platelet function]. Zhonghua Xue Ye Xue Za Zhi. 2014 Oct;35(10):905-8. Chinese. doi: 10.3760/cma.j.issn.0253-2727.2014.10.007. PMID: 25339327. 3. Muhedier M, Li J, Liu H, Ma G, Amahong K, Lin R, Lü G. Tacrolimus, a rapamycin target protein inhibitor, exerts anti-cystic echinococcosis effects both in vitro and in vivo. Acta Trop. 2020 Dec;212:105708. doi: 10.1016/j.actatropica.2020.105708. Epub 2020 Sep 18. PMID: 32956634. |
| In vitro protocol: | 1. Lee WS, Jeong JH, Lee EG, Choi Y, Kim JH, Kim HR, Yoo WH. Tacrolimus regulates endoplasmic reticulum stress-mediated osteoclastogenesis and inflammation: In vitro and collagen-induced arthritis mouse model. Cell Biol Int. 2018 Apr;42(4):393-402. doi: 10.1002/cbin.10861. Epub 2018 Jan 24. PMID: 28833755. 2. DU C, Wang X, Zhao L, Dai K. [In vitro effects of tacrolimus on platelet function]. Zhonghua Xue Ye Xue Za Zhi. 2014 Oct;35(10):905-8. Chinese. doi: 10.3760/cma.j.issn.0253-2727.2014.10.007. PMID: 25339327. |
| In vivo protocol: | 1. Lee WS, Jeong JH, Lee EG, Choi Y, Kim JH, Kim HR, Yoo WH. Tacrolimus regulates endoplasmic reticulum stress-mediated osteoclastogenesis and inflammation: In vitro and collagen-induced arthritis mouse model. Cell Biol Int. 2018 Apr;42(4):393-402. doi: 10.1002/cbin.10861. Epub 2018 Jan 24. PMID: 28833755. 2. Muhedier M, Li J, Liu H, Ma G, Amahong K, Lin R, Lü G. Tacrolimus, a rapamycin target protein inhibitor, exerts anti-cystic echinococcosis effects both in vitro and in vivo. Acta Trop. 2020 Dec;212:105708. doi: 10.1016/j.actatropica.2020.105708. Epub 2020 Sep 18. PMID: 32956634. |
1: Penninga L, Penninga EI, Møller CH, Iversen M, Steinbrüchel DA, Gluud C. Tacrolimus versus cyclosporin as primary immunosuppression for lung transplant recipients. Cochrane Database Syst Rev. 2013 May 31;5:CD008817. doi: 10.1002/14651858.CD008817.pub2. Review. PubMed PMID: 23728681.
2: Sekiguchi Y, Shimada A, Imai H, Wakabayashi M, Sugimoto K, Nakamura N, Sawada T, Komatsu N, Noguchi M. Epstein-Barr virus-negative, CD5-positive diffuse large B-cell lymphoma developing after treatment with oral tacrolimus for mixed connective tissue disease : a case report and review of the literature. J Clin Exp Hematop. 2012;52(3):211-8. Review. PubMed PMID: 23269082.
3: Remitz A, Reitamo S. Long-term safety of tacrolimus ointment in atopic dermatitis. Expert Opin Drug Saf. 2009 Jul;8(4):501-6. doi: 10.1517/14740330902969441 . Review. PubMed PMID: 19435404.
4: Sánchez-Pérez J. [Safety information for tacrolimus: present and future]. Actas Dermosifiliogr. 2008 Feb;99 Suppl 2:19-25. Review. Spanish. PubMed PMID: 18346426.
5: Torrelo A. [Topical tacrolimus in atopic dermatitis in children]. Actas Dermosifiliogr. 2008 Feb;99 Suppl 2:14-8. Review. Spanish. PubMed PMID: 18346425.
6: Ortiz de Frutos FJ. [Atopic dermatitis and tacrolimus in adults]. Actas Dermosifiliogr. 2008 Feb;99 Suppl 2:8-13. Review. Spanish. PubMed PMID: 18346424.
7: Rustin MH. The safety of tacrolimus ointment for the treatment of atopic dermatitis: a review. Br J Dermatol. 2007 Nov;157(5):861-73. Epub 2007 Sep 13. Review. PubMed PMID: 17854353.
8: Sánchez-Pérez J. [Topical pimecrolimus and tacrolimus and the risk of cancer]. Actas Dermosifiliogr. 2007 Jun;98(5):312-7. Review. Spanish. PubMed PMID: 17555673.
9: van Dieren JM, Kuipers EJ, Samsom JN, Nieuwenhuis EE, van der Woude CJ. Revisiting the immunomodulators tacrolimus, methotrexate, and mycophenolate mofetil: their mechanisms of action and role in the treatment of IBD. Inflamm Bowel Dis. 2006 Apr;12(4):311-27. Review. PubMed PMID: 16633053.
10: Ormerod AD. Topical tacrolimus and pimecrolimus and the risk of cancer: how much cause for concern? Br J Dermatol. 2005 Oct;153(4):701-5. Review. PubMed PMID: 16181449.
11: Dé Tran QH, Guay E, Chartier S, Tousignant J. Tacrolimus in dermatology. J Cutan Med Surg. 2001 Jul-Aug;5(4):329-35. Epub 2001 May 2. Review. PubMed PMID: 11907845.
12: Nghiem P, Pearson G, Langley RG. Tacrolimus and pimecrolimus: from clever prokaryotes to inhibiting calcineurin and treating atopic dermatitis. J Am Acad Dermatol. 2002 Feb;46(2):228-41. Review. PubMed PMID: 11807435.
13: Woo M, Przepiorka D, Ippoliti C, Warkentin D, Khouri I, Fritsche H, Körbling M. Toxicities of tacrolimus and cyclosporin A after allogeneic blood stem cell transplantation. Bone Marrow Transplant. 1997 Dec;20(12):1095-8. Review. PubMed PMID: 9466284.
Anna Roszkowska, Natalia Treder, Alina Plenis, Natalia Miękus, Ilona Olędzka, Piotr Kowalski, Tomasz Bączek, Optimization and comparison of two microsampling approaches for LC-MS/MS analysis of a panel of immunosuppressants in blood samples, Sustainable Chemistry and Pharmacy, Volume 21, 2021, 100433, ISSN 2352-5541, https://doi.org/10.1016/j.scp.2021.100433. (https://www.sciencedirect.com/science/article/pii/S2352554121000607)
