Tacrolimus

FK506Prograftacrolimus binding protein 1atacrolimus binding proteinsFK 506FK-506Protopictacrolimus (FK506)tacrolism
Tacrolimus, also known as fujimycin or FK506, is an immunosuppressive drug used mainly after allogeneic organ transplant to lower the risk of organ rejection.wikipedia
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Streptomyces tsukubaensis

Chemically it is a 23-membered macrolide lactone that was first discovered in 1987 from the fermentation broth of a Japanese soil sample that contained the bacterium Streptomyces tsukubaensis.
It produces the immunosuppressive drug tacrolimus.

Transplant rejection

rejectiongraft rejectionorgan rejection
Tacrolimus, also known as fujimycin or FK506, is an immunosuppressive drug used mainly after allogeneic organ transplant to lower the risk of organ rejection.

Nephrotoxicity

nephrotoxicnephrotoxinKidney damage
Side effects can be severe and include infection, cardiac damage, hypertension, blurred vision, liver and kidney problems (tacrolimus nephrotoxicity), hyperkalemia, hypomagnesemia, hyperglycemia, diabetes mellitus, itching, lung damage (sirolimus also causes lung damage), and various neuropsychiatric problems such as loss of appetite, insomnia, posterior reversible encephalopathy syndrome, confusion, weakness, depression, vivid nightmares, cramps, neuropathy, seizures, tremors, and catatonia.

Vitiligo

leucodermaleukodermaTrichrome vitiligo
(for which it is applied to the skin in a medicated ointment), severe refractory uveitis after bone marrow transplants, exacerbations of minimal change disease, Kimura's disease, and the skin condition vitiligo.
Topical preparations of immune suppressing medications including glucocorticoids (such as 0.05% clobetasol or 0.10% betamethasone) and calcineurin inhibitors (such as tacrolimus or pimecrolimus) are considered to be first-line vitiligo treatments.

Atopic dermatitis

atopic eczemaatopiceczema
Tacrolimus is also used in the treatment of other T cell-mediated diseases such as eczema and psoriasis. As an ointment, tacrolimus is used in the treatment of eczema, in particular atopic dermatitis.
If topical corticosteroids and moisturisers fail, short-term treatment with topical calcineurin inhibitors like tacrolimus or pimecrolimus may be tried, although their use is controversial as some studies indicate that they increase the risk of developing skin cancer or lymphoma.

Hyperkalemia

high blood potassiumhyperkalaemiahigh blood potassium levels
Side effects can be severe and include infection, cardiac damage, hypertension, blurred vision, liver and kidney problems (tacrolimus nephrotoxicity), hyperkalemia, hypomagnesemia, hyperglycemia, diabetes mellitus, itching, lung damage (sirolimus also causes lung damage), and various neuropsychiatric problems such as loss of appetite, insomnia, posterior reversible encephalopathy syndrome, confusion, weakness, depression, vivid nightmares, cramps, neuropathy, seizures, tremors, and catatonia.
Examples of medications that can cause hyperkalemia include ACE inhibitors, angiotensin receptor blockers, beta blockers, and calcineurin inhibitor immunosuppressants such as ciclosporin and tacrolimus.

Macrolide

macrolidesmacrolide antibioticmacrolide antibiotics
Chemically it is a 23-membered macrolide lactone that was first discovered in 1987 from the fermentation broth of a Japanese soil sample that contained the bacterium Streptomyces tsukubaensis.
The drugs tacrolimus, pimecrolimus, and sirolimus, which are used as immunosuppressants or immunomodulators, are also macrolides.

Kimura's disease

Kimura disease
(for which it is applied to the skin in a medicated ointment), severe refractory uveitis after bone marrow transplants, exacerbations of minimal change disease, Kimura's disease, and the skin condition vitiligo.
Tacrolimus (FK-506) was administered at an initial dosage of 1 mg every 12 hours, and FK-506 concentration in the blood was monitored monthly.

Mycophenolic acid

mycophenolate mofetilmycophenolateCellcept
Tacrolimus is normally prescribed as part of a post-transplant cocktail including steroids, mycophenolate, and IL-2 receptor inhibitors such as basiliximab.
It is usually used as part of a three-compound regimen of immunosuppressants, also including a calcineurin inhibitor (ciclosporin or tacrolimus) and a glucocorticoid (e.g decadron or prednisone).

Minimal change disease

lipoid nephrosisMinimal change lesionminimal change nephropathy
(for which it is applied to the skin in a medicated ointment), severe refractory uveitis after bone marrow transplants, exacerbations of minimal change disease, Kimura's disease, and the skin condition vitiligo.
Data in adults is less complete in comparison to children but relapses are also fairly frequent with 56-76% of patients relapsing and need further treatment with immunosuppressants, such as ciclosporin, tacrolimus, mycophenolate, and rituximab.

Calcineurin

Calcineurin APPP3
In T-cells, activation of the T-cell receptor normally increases intracellular calcium, which acts via calmodulin to activate calcineurin.
Calcineurin is the target of a class of drugs called calcineurin inhibitors, which include ciclosporin, voclosporin, pimecrolimus and tacrolimus.

Dermatitis

eczemaallergic dermatitischronic eczema
As an ointment, tacrolimus is used in the treatment of eczema, in particular atopic dermatitis.
Topical immunosuppressants like pimecrolimus and tacrolimus may be better in the short term and appear equal to steroids after a year of use.

FKBP1A

FKBP12FK binding protein-12FKBPP12
In detail, tacrolimus reduces peptidylprolyl isomerase activity by binding to the immunophilin FKBP12 (FK506 binding protein), creating a new complex.
This encoded protein is a cis-trans prolyl isomerase that binds the immunosuppressants FK506 (tacrolimus) and rapamycin (sirolimus).

Sirolimus

rapamycinRapamune
Side effects can be severe and include infection, cardiac damage, hypertension, blurred vision, liver and kidney problems (tacrolimus nephrotoxicity), hyperkalemia, hypomagnesemia, hyperglycemia, diabetes mellitus, itching, lung damage (sirolimus also causes lung damage), and various neuropsychiatric problems such as loss of appetite, insomnia, posterior reversible encephalopathy syndrome, confusion, weakness, depression, vivid nightmares, cramps, neuropathy, seizures, tremors, and catatonia.
Sirolimus can also be used alone, or in conjunction with a calcineurin inhibitor (such as tacrolimus), and/or mycophenolate mofetil, to provide steroid-free immunosuppression regimens.

Pimecrolimus

Elidel
Tacrolimus and a related drug for eczema (pimecrolimus) were suspected of carrying a cancer risk, though the matter is still a subject of controversy.
In January 2006, the United States Food and Drug Administration (FDA) announced that Elidel packaging would be required to carry a black box warning regarding the potential increased risk of lymph node or skin cancer, as for the similar drug tacrolimus.

Immunosuppressive drug

immunosuppressantcalcineurin inhibitorimmunosuppressive drugs
Tacrolimus, also known as fujimycin or FK506, is an immunosuppressive drug used mainly after allogeneic organ transplant to lower the risk of organ rejection.
Like tacrolimus, ciclosporin (Novartis' Sandimmune) is a calcineurin inhibitor (CNI).

Liver transplantation

liver transplanttransplantliver
Tacrolimus was first approved by the Food and Drug Administration in 1994 for use in liver transplantation; this has been extended to include kidney, heart, small bowel, pancreas, lung, trachea, skin, cornea, bone marrow, and limb transplants.
Most liver transplant recipients receive corticosteroids plus a calcineurin inhibitor such as tacrolimus or ciclosporin, (also spelled cyclosporine and cyclosporin) plus a purine antagonist such as mycophenolate mofetil.

FK1012

FK1012, a derivative of tacrolimus, is used as a research tool in chemically induced dimerization applications.

Stuart Schreiber

Stuart L. SchreiberSchreiber
Notable accomplishments include the total syntheses of complex natural products such as talaromycin B, asteltoxin, avenaciolide, gloeosporone, hikizimicin, mycoticin A, epoxydictymene and the immunosuppressant FK-506.

Astellas Pharma

AstellasYamanouchi PharmaceuticalAstellas Pharma Inc.
The branded version of the drug is owned by Astellas Pharma, and is sold under the trade name Prograf, given twice daily.

Voriconazole

Vfendvoriconaozle
Macrolide antibiotics including erythromycin and clarithromycin, as well as several of the newer classes of antifungals, especially of the azole class (fluconazole, voriconazole), increase tacrolimus levels by competing for cytochrome enzymes.
Voriconazole should not be used in conjunction with many drugs including sirolimus, rifampicin, rifabutin, carbamazepine, quinidine and ergot alkaloids) and dose adjustments and/or monitoring when coadministered with others (including fluconazole, warfarin, ciclosporin, tacrolimus, omeprazole, and phenytoin).

NFAT

Nuclear factor of activated T-cellsNF-ATnuclear factor of activated T cells
Calcineurin then dephosphorylates the transcription factor nuclear factor of activated T-cells (NF-AT), which moves to the nucleus of the T-cell and increases the activity of genes coding for IL-2 and related cytokines.
CN inhibitors, which prevent the activation of NFAT, including cyclosporine (CsA) and tacrolimus (FK506), are used in the treatment of rheumatoid arthritis, multiple sclerosis, Crohn's disease, and ulcerative colitis and to prevent the rejection of organ transplants.

Tohru Kino

Tohru Kino is a Japanese chemist and pharmacologist, best known for his discovery of tacrolimus.