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Tacrolimus is a 23-membered macrolide lactone, it reduces peptidyl-prolyl isomerase activity in T cells by binding to the immunophilin creating a new complex.
Solubility: 94 mg/mL in DMSO
Insoluble in water
Targets FKBP12 (T cells)
In vitro: Tacrolimus and cyclosporin A block translocation of the cytoplasmic component without affecting synthesis of the nuclear subunit in T lymphocytes. It prevents T-cell proliferation by inhibiting a Ca(2+)-dependent event required for induction of interleukin-2 transcription. It binds to distinct families of intracellular proteins (immunophilins) termed cyclophilins and FK 506-binding proteins (FKBPs). It specifically inhibits cellular calcineurin at drug concentrations that inhibit interleukin 2 production in activated T cells. Tacrolimus and CsA exert nearly identical biological effects in cells by inhibiting the same subset of early calcium-associated events involved in lymphokine expression, apoptosis, and degranulation.
In vivo: Tacrolimus results in increase in the paw and tail withdrawal threshold as revealed by behavioral pain assessment in rats against hyperalgesic and allodynic stimuli. It also leads to a decrease in the serum nitrate and thiobarbituric acid reactive substance (TBARS) levels along with reduction in tissue myeloperoxidase (MPO) and total calcium levels, whereas, rise in tissue reduced glutathione levels in rats. It ameliorates the increase in the neuronal edema and axonal degeneration in rats with ischemia reperfusion