Target type: biologicalprocess
Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a tacrolimus stimulus. [GOC:TermGenie]
Tacrolimus, also known as FK506, is an immunosuppressant drug widely used to prevent organ transplant rejection. It exerts its effects by targeting the calcineurin signaling pathway, a key regulator of immune cell activation.
Tacrolimus binds to FK506-binding protein 12 (FKBP12), forming a complex that inhibits the phosphatase activity of calcineurin. Calcineurin, a calcium-dependent protein phosphatase, normally dephosphorylates the transcription factor NFAT (nuclear factor of activated T cells). Dephosphorylation of NFAT allows its translocation into the nucleus, where it activates the transcription of genes involved in T cell activation, cytokine production, and proliferation.
By inhibiting calcineurin, tacrolimus prevents NFAT dephosphorylation and nuclear translocation, effectively blocking T cell activation. This suppression of T cell activity prevents the immune system from recognizing and attacking the transplanted organ.
The biological process of response to tacrolimus can be summarized as follows:
1. **Binding to FKBP12:** Tacrolimus binds to FKBP12, a cytosolic protein.
2. **Inhibition of Calcineurin:** The tacrolimus-FKBP12 complex binds to and inhibits calcineurin, a calcium-dependent phosphatase.
3. **NFAT Phosphorylation:** Inhibition of calcineurin prevents the dephosphorylation of NFAT.
4. **NFAT Retention in the Cytoplasm:** NFAT remains phosphorylated and is unable to translocate into the nucleus.
5. **Suppression of T Cell Activation:** The inability of NFAT to activate target genes leads to suppression of T cell activation, proliferation, and cytokine production.
This chain of events ultimately prevents the immune system from mounting a rejection response against the transplanted organ.'
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| Protein | Definition | Taxonomy |
|---|---|---|
| C-X-C chemokine receptor type 4 | A C-X-C chemokine receptor type 4 that is encoded in the genome of human. [PRO:WCB, UniProtKB:P61073] | Homo sapiens (human) |
| Interleukin-2 | An interleukin-2 that is encoded in the genome of human. [PRO:CNA, UniProtKB:P60568] | Homo sapiens (human) |
| Compound | Definition | Classes | Roles |
|---|---|---|---|
| zalcitabine | zalcitabine : A pyrimidine 2',3'-dideoxyribonucleoside compound having cytosine as the nucleobase. Zalcitabine: A dideoxynucleoside compound in which the 3'-hydroxy group on the sugar moiety has been replaced by a hydrogen. This modification prevents the formation of phosphodiester linkages which are needed for the completion of nucleic acid chains. The compound is a potent inhibitor of HIV replication at low concentrations, acting as a chain-terminator of viral DNA by binding to reverse transcriptase. Its principal toxic side effect is axonal degeneration resulting in peripheral neuropathy. | pyrimidine 2',3'-dideoxyribonucleoside | antimetabolite; antiviral drug; HIV-1 reverse transcriptase inhibitor |
| plerixafor | plerixafor : An azamacrocycle consisting of two cyclam rings connected by a 1,4-phenylenebis(methylene) linker. It is a CXCR4 chemokine receptor antagonist and a hematopoietic stem cell mobilizer. It is used in combination with grulocyte-colony stimulating factor (G-CSF) to mobilize hematopoietic stem cells to the perpheral blood for collection and subsequent autologous transplantation in patients with non-Hodgkin's lymphoma and multiple myeloma. plerixafor: a bicyclam derivate, highly potent & selective inhibitor of HIV-1 & HIV-2 | azacycloalkane; azamacrocycle; benzenes; crown amine; secondary amino compound; tertiary amino compound | anti-HIV agent; antineoplastic agent; C-X-C chemokine receptor type 4 antagonist; immunological adjuvant |
| benzylaniline | benzylaniline: major metabolite of antazoline; RN given refers to parent cpd | ||
| terephthalamide | benzenedicarboxamide | ||
| daidzin | daidzein 7-O-beta-D-glucoside : A glycosyloxyisoflavone that is daidzein attached to a beta-D-glucopyranosyl residue at position 7 via a glycosidic linkage. It is used in the treatment of alcohol dependency (antidipsotropic). daidzin: a potent, selective, and reversible inhibitor of human mitochondrial aldehyde dehydrogenase | 7-hydroxyisoflavones 7-O-beta-D-glucoside; hydroxyisoflavone; monosaccharide derivative | plant metabolite |
| ononin | 4'-methoxyisoflavones; 7-hydroxyisoflavones 7-O-beta-D-glucoside; monosaccharide derivative | plant metabolite | |
| krh 1636 | KRH 1636: structure in first source | ||
| amd 8664 | |||
| cyclo(d-tyrosyl-arginyl-arginyl-3-(2-naphthyl)alanyl-glycyl) | oligopeptide | ||
| formononetin | 4'-methoxyisoflavones; 7-hydroxyisoflavones | phytoestrogen; plant metabolite | |
| luteolin-7-glucoside | luteolin 7-O-beta-D-glucoside : A glycosyloxyflavone that is luteolin substituted by a beta-D-glucopyranosyl moiety at position 7 via a glycosidic linkage. luteolin-7-glucoside: has both antiasthmatic and antineoplastic activities; has 3C protease inhibitory activity; isolated from Ligustrum lucidum | beta-D-glucoside; glycosyloxyflavone; monosaccharide derivative; trihydroxyflavone | antioxidant; plant metabolite |
| N(2)-carbamimidoyl-N-{2-[4-(3-{4-[(5-carboxyfuran-2-yl)methoxy]-2,3-dichlorophenyl}-1-methyl-1H-pyrazol-5-yl)piperidin-1-yl]-2-oxoethyl}-D-leucinamide | N(2)-carbamimidoyl-N-{2-[4-(3-{4-[(5-carboxyfuran-2-yl)methoxy]-2,3-dichlorophenyl}-1-methyl-1H-pyrazol-5-yl)piperidin-1-yl]-2-oxoethyl}-D-leucinamide : A leucine derivative obtained by fpormal condensation of the secondary amino group of 5-({2,3-dichloro-4-[1-methyl-5-(piperidin-4-yl)-1H-pyrazol-3-yl]phenoxy}methyl)-2-furoic acid and the carboxy group of N-amidino-L-leucylglycine | D-leucine derivative; dichlorobenzene; furoic acid; glycine derivative; guanidines; pyrazolylpiperidine | |
| calycosin-7-o-beta-d-glucopyranoside | calycosin-7-O-beta-D-glucoside : A glycosyloxyisoflavone that is calycosin substituted by a beta-D-glucopyranosyl residue at position at 7 via a glycosidic linkage. calycosin-7-O-beta-D-glucoside: from Radix Astragali | 4'-methoxyisoflavones; 7-hydroxyisoflavones 7-O-beta-D-glucoside; hydroxyisoflavone; monosaccharide derivative | |
| amd 070 | mavorixafor: a derivative of AMD3100; a CXCR4 blocker | aminoquinoline | |
| wz 811 | |||
| diosgenin glucoside | diosgenin 3-O-beta-D-glucoside : A sterol 3-beta-D-glucoside having diosgenin as the sterol component. diosgenin glucoside: RN given refers to (3beta,25R)-isomer; structure given in first source | hexacyclic triterpenoid; monosaccharide derivative; spiroketal; sterol 3-beta-D-glucoside | metabolite |
| tn14003 | TN14003: synthetic antagonist 14-mer peptide inhibiting metastasis in an animal model |