Tacrolimus is a powerful immuno-suppressant drug. It is a macrolide produced by Streptomyces species through fermentation path way. Tacrolimus (FK 506), a hydrophobic lactone, macrolide antibiotic, is a potent immunosuppressive agent classified as an anticalcineurin drug. Tacrolimus binds to a family of proteins termed FK 506 binding proteins (FKBPs).
Tacrolimus has been demonstrated to suppress humoral immunity and to a greater extent cell mediated reactions such as allograft rejection, delayed hypersensitivity, collagen induced arthritis, experimental allergic encephalomyelitis and used as dermatological preparations to treat Atopic dermatitis etc.
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Mode of action
Tacrolimus reduces peptidyl-prolyl isomerase activity by binding to the immunophilin FKBP-12 (FK506 binding protein) creating a new complex. This FKBP12-FK506 complex interacts with and inhibits calcineurin thus inhibiting both T-lymphocyte signal transduction and IL-2 transcription. The action of transcription factors requiring dephosphorylation is thus inhibited, leading to the blockade of interleukin-2 gene transcription, an early event in the immunological cascade.
Tacrolimus is also known to suppress the early stage T-cell activation by inhibiting the transcription for genes which encode IL-3, IL-4, IL-5, GM-CSF, and TNF.
Although this immuno-suppressant activity is similar to cyclosporine, studies have shown that the incidence of acute rejection during organ transplants is reduced by Tacrolimus use over cyclosporine.
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Uses
Tacrolimus is widely used in organ transplantation, to prevent graft rejection. It is used in case of Liver, Kidney, Heart or any such organ transplants to prevent the rejection by the recipient body’s immunological system.
It is also used as a topical preparation in the treatment of severe Atopic dermatitis and in cases of resistant Psoriasis.
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Tacrolimus, a powerful immuno-suppressant drug is produced from the fungal cultures, Streptomyces tukkugudaensis. S. tukkugudaensis. is a culture that has been identified in a remote village of India and carefully cultivated through years of hard work at the R&D department. The drug has gone through series quality control assays prior to reaching a stage of commercial production.
This drug is produced in a series of large fermentors under the strict cGMP conditions. The raw bulk produced from the fermentation process is processed employing various purification steps and the final purified bulk drug emerges in dry crystalline form.
Quality Control Department at Transgene undertakes the rigorous assay procedures at each step of the production and purification process and finally, prior to dispatch of each consignment. Every gram of Tacrolimus at Transgene conforms to a detailed and specified series of quality control assays.
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INTRODUCTION
Tacrolimus is a macrolide immunosuppressant produced by Streptomyces species through fermentation path way. It is an 822 D immunosuppressant of the macrolide family. It appears as a white crystal powder with the molecular formula C44H69NO12. Tacrolimus has been demonstrated to suppress humoral immunity and to a greater extent cell mediated reactions such as allograft rejection, delayed hypersensitivity, collagen induced arthritis, experimental allergic encephalomyelitis, and graft versus host disease.
INTENDED USES:
- Tacrolimus is widely used in organ transplantation, to prevent graft rejection. It is indicated for the prophylaxis of organ rejection in patients receiving allogeneic liver or kidney transplants.
- Used in a topical preparation in the treatment of severe atopic dermatitis and Psoriasis.
- Used after bone marrow transplants and for severe refractory uveitis.
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MODE OF ACTION
Tacrolimus is a macrolide and it acts by binding to an intracellular protein, immunophilin FKBP-12 through reduction of peptidyl-prolyl isomerase activity and forming a new complex of Tacrolimus-FKBP-12, calcium, calmodulin, and calcineurin. This complex inhibits the phosphatase activity of calcineurinand prevents the dephosphorylation and translocation of nuclear factor of activated T-cells (NF-AT), a nuclear component thought to initiate gene transcription for the formation of lymphokines.
Tacrolimus is also known to suppress the early stage T-cell activation by inhibiting the transcription for genes which encode IL-3, IL-4, IL-5, GM-CSF, and TNF.
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Additionally, Tacrolimus has been shown to inhibit the release of pre-formed mast cells and basophills, and to down-regulate the expression of FceRI on Langerhans cells.
SUMMARY
Tacrolimus reduces the activity of patient’s immune system and in doing so, reduces the risk of rejection during various organ transplants such as kidney, heart, skin, cornea, and limb transplants. It has also been used in a topical preparation in the treatment of severe atopic dermatitis and Psoriasis.
Tacrolimus at Transgene has been the result of an extensive research spanning over several years. The drug is produced by fungus, Streptomyces tukkugudaensis, isolated at a remote area in India. Tacrolimus is now ready to be produced in Kilogram quantities at cGMP compliant facilities.
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