Tacrolimus monohydrate
[CAS# 109581-93-3]

Identification

• Classification: Biochemical >> Inhibitor >> Immune inhibitor
• Name: Tacrolimus monohydrate
• Synonyms: (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;hydrate
• Molecular Formula: C₄₄H₆₉NO₁₂.H₂O
• Molecular Weight: 822.03
• CAS Registry Number: 109581-93-3
• EC Number: 634-559-2
• 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.O

Safety Data

• Hazard Symbols: GHS06 Danger
• Risk Statements: H301
• Safety Statements: P264-P270-P301+P316-P321-P330-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Acute toxicity	Acute Tox.	3	H301
Specific target organ toxicity - repeated exposure	STOT RE	1	H372
Reproductive toxicity	Repr.	2	H361
Acute toxicity	Acute Tox.	3	H311
Acute toxicity	Acute Tox.	3	H331
Eye irritation	Eye Irrit.	2	H319
Specific target organ toxicity - single exposure	STOT SE	3	H335
Carcinogenicity	Carc.	2	H351
Reproductive toxicity	Repr.	1B	H360FD
Skin irritation	Skin Irrit.	2	H315

• Transport Information: UN 2811

Discovery and Applications

Tacrolimus, also known as FK506, was discovered in the 1980s by researchers at Fujisawa Pharmaceutical Co., Ltd. The discovery was serendipitous, as it was initially identified as a metabolite produced by the bacterium Streptomyces tsukubaensis during a search for novel immunosuppressive agents. Tacrolimus exhibited potent immunosuppressive properties, particularly in inhibiting T-cell activation, making it a promising candidate for the prevention of organ rejection in transplantation.

Tacrolimus monohydrate revolutionized organ transplantation by significantly improving graft survival rates. As a calcineurin inhibitor, tacrolimus inhibits T-cell activation by binding to the protein FKBP-12, thereby disrupting the signaling pathway required for T-cell activation. It is widely used in solid organ transplantation, particularly in kidney and liver transplants, to prevent acute rejection episodes and improve long-term graft survival. Tacrolimus-based immunosuppressive regimens have become standard of care in transplantation medicine. Tacrolimus has found applications beyond transplantation in the treatment of various autoimmune diseases. It is used off-label in conditions such as rheumatoid arthritis, psoriasis, and inflammatory bowel disease, where aberrant immune responses play a central role in disease pathogenesis. Tacrolimus suppresses the immune system's inflammatory response, providing symptomatic relief and improving disease outcomes in patients with autoimmune disorders. Topical formulations of tacrolimus are used in the treatment of certain dermatologic conditions, such as atopic dermatitis and psoriasis. Tacrolimus ointment acts as an immunomodulator, reducing inflammation and pruritus associated with these conditions. Its use is particularly beneficial in sensitive areas of the skin or when prolonged use of corticosteroids is not desirable. Tacrolimus is also used in the prevention and treatment of graft-versus-host disease (GVHD), a common complication of allogeneic hematopoietic stem cell transplantation. By suppressing the immune response of donor-derived T cells against recipient tissues, tacrolimus helps mitigate the risk of acute and chronic GVHD, improving outcomes in patients undergoing stem cell transplantation.

References

2014. Topical Therapy II: Retinoids, Immunomodulators, and Others. Advances in Psoriasis.
DOI: 10.1007/978-1-4471-4432-8_7

1998. Tacrolimus Eliminates Acute Rejection as a Major Complication Following Simultaneous Kidney and Pancreas Transplantation. Transplantation Proceedings.
DOI: 10.1016/s0041-1345(97)01379-1

1998. Effect of Tacrolimus Hydrate (FK506) Ointment on Spontaneous Dermatitis in NC/Nga Mice. Japanese Journal of Pharmacology.
DOI: 10.1254/jjp.76.175