dale1994's version from 2016-05-01 14:20
|Azathioprine||(non-specific) antimetabolite. |
A prodrug that is activated in the body, slowly converted to 6-merc by reductive cleavage of the thioether.
Mediated by glutathione in the intestinal wall, RBC and liver without enzymes.
Active metabolite is thioinosine monophosphate a purine synthesis inhibitor which works by blocking the enzyme amidophosphoribosyl transferase.
Blocks purine synthesis which hinders DNA synthesis and thus inhibits the proliferation of cells, especially fast growing cells (T & B cells)
|Cyclophosphamide||(alkylating agent:non-specifc) |
rapidly absorbed and converted in the liver by the P450 cytochrome system to active metabolites.
The main active form is aldophosphamide.
Attached alkyl group to guanine base of DNA at the number 7 nitrogen atom on the imidazole ring.
Interferes with DNA rep by forming intrastrand and interstrand crosslinks.
High toxicity, bladder cancer, teratogenic.
|Mycophenolic Acid||(Non specific) |
Mycophenolate mofetil converting to mycophenolic acid in the body.
Reversibly inhibits inosine monophophate dehydrogenase, the enzyme that controls the rate of synthesis of guanine monophosphate in the de novo pathway of purine synthesis used in T & B cell proliferation.
Usually used with a calcineurin inhibitor.
Non-competitive enzyme inhibitor & allosteric regulator of activity.
|Anti-Lymphocytic Globulin (ALG)||Infusion of animal AB against human T cells. |
Large animals IgG fraction is purified and the antigen is human lymphoid cells.
Bind to surface of Ag-recognising T cells.
Cytotoxic by serum complement with specific destruction of T cells.
Interferes with the activity and growth of T cells.
Binds in cell cytoplasm to the protein cyclophilin and the complex associates with and inhibits calcineurin, a calmodulin Ca2+-dependent phosphatase which is a key component in T cell activation.
Inhibiting calcineurin prevens the dephosphorylate of NFAT which prevents NFATs translocation to the nucleus and thus inhibits Il-2 production and
T cell cycle is inhibited in between G0 and G1.
|FK506 (Tacrolimus)||Inhibits T cell proliferation. |
Arrests cel cycle between G0 and G1.
After binding to receptor protein called FK binding protein-12 the complex binds to calcineurin and inhibits the activation.
Prevents dephosphorylation of NFAt and thus suppresses T cell activation.
|Rapamycin||Inhibits Il-2 production. |
Arrests cell cycle between G1 and S phase.
Binds to FKBP12 and inhibits action of cytoplasmic kinase mTOR/ mTOR is a key step in a series of Ca2+-independent events that transduce cell surface signals from IL-2 receptor to cell cycle regulators that promote DNA and protein synthesis.