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外観
白色〜ほとんど白色, 結晶〜粉末
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溶解性
アセトニトリルに溶ける。
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用途
強 力 な 免疫抑制剤 で す。
FK506はFK506結合タンパク-12(FKBP12)
と複合体を形成し、さらにカルシニューリン
に結合し、IL-2、インターフェロンに代表さ
れる種々のサイトカインの発現を抑制しま
す。これにより細胞外性 T 細胞の分化増殖を
抑制します。
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効能
抗アレルギー薬, 免疫抑制薬, カルシニューリン阻害薬
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説明
Tacrolimus, isolated from the microorganism Streptomyces tsukubaensis, is a
macrolide immunosuppressant developed by Fujisawa for organ transplantation. It displays
similar but more potent immunosuppressive activity than cyclosporin. It inhibits both cell
mediated and humoral immune responses. In animal models of organ transplantation,
tacrolimus has been shown to prolong survival of hepatic, renal, cardiac, small intestine,
pancreatic and skin allografts and to reverse cardiac and renal allograft rejection. It has been
used effectively in humans as rescue or primary immunosuppressant therapy in liver or kidney
transplantation. Compared to cyclosporin, tacrolimus causes reduced incidence of infectious
complications and of hypertension and hypercholesterolemia for the allograft recipients. In
common with cyclosporin, tacrolimus binds with high affinity to a family of cytoplasmic
immunosuppressant binding proteins, the immunophilins. This tight complex is proposed as
the biologically active moiety that interacts with intracellular molecules involved in signal
transduction.It inhibits phosphatase activity of calcineurin, an action that may impair the
generation and/or activation of nuclear transcription factors required for lymphokine
(particularly interleukin-2) gene expression. Tacrolimus has also been reported to have
potential in multiple sclerosis, psoriasis, rheumatoid arthritis and uveitis associated with
Behcet‘s disease.
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化学的特性
White Crystalline Solid
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使用
FK-506 (Tacrolimus) is a macrolide immunosuppressive drug that is mainly used after allogeneic organ transplant to reduce the activity of the patient's immune system
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適応症
Tacrolimus is a macrolide lactone originally derived
from Streptomyces tsukubaensis. Although structurally
unrelated to cyclosporine, tacrolimus has a very similar
mechanism of action; that is, it blocks the production of
proinflammatory cytokines by T lymphocytes by inhibiting
calcineurin.Tacrolimus, however, appears to be
10 to 100 times as potent as an immunosuppressive.
Oral tacrolimus (FK506) is used for prevention of organ
rejection in recipients of renal and hepatic transplants.
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定義
ChEBI: Tacrolimus is a macrolide containing a 23-membered lactone ring, originally isolated from the fermentation broth of a Japanese soil sample that contained the bacteria Streptomyces tsukubaensis.
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一般的な説明
Immunosuppressant that blocks T-cell proliferation in vitro by inhibiting the generation of several lymphokines, especially IL-2. Shown to inhibit the activity of FK-506 Binding Protein, thereby reversing its effects on sarcoplamic reticulum Ca2+ release. Shown to inhibit the Ca2+-dependent phosphatase, Calcineurin (Cat. No. 539565), as well as Na+-K+-ATPase in nephron segments. Also shown to inhibit aldosterone-induced synthesis of Giα-3 protein.
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臨床応用
A topical formulation (Protopic) has recently been approved
for treatment of moderate to severe atopic dermatitis
in children and adults who have not responded
to other therapies. Levels of systemic absorption are
low even when applied to a relatively large body surface
area.
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副作用
Local irritant reactions (burning, stinging, erythema)
are a common side effect, but these usually resolve
within the first few days of treatment. The major
benefit of topical tacrolimus over topical corticosteroids
is that tacrolimus does not cause atrophy, striae, or
telangiectasia, even with chronic use.