<s>[INST] context: ANTIMETABOLITES These are analogues related to normal components of DNA or of coenzymes involved in nucleic acid synthesis. They competitively inhibit utilization of the normal substrate or get themselves incorporated forming dysfunctional macromolecules. Methotrexate (Mtx): It is one of the oldest and highly efficacious antineoplastic drugs; inhibits dihydrofolate reductase (DHFRase)-blocking the conversion of dihydrofolic acid (DHFA) to tetrahydrofolic acid (THFA) which is an essential coenzyme required for one carbon transfer reactions in de novo purine synthesis and amino acid interconversions. The inhibition is pseudoirreversible because Mtx has 50,000 times higher affinity for the enzyme than the normal substrate. Calcineurin inhibitors: (Specific T-cell inhibitors) >Cyclosporine :It is a cyclic polypeptide with 11 amino acids, obtained from a fungus and introduced in 1977 as a highly selective immunosuppressant which has markedly increased the success of organ transplantations. It profoundly and selectively inhibits T lymphocyte proliferation, IL-2 and other cytokine production and response of inducer T cells to IL-l, without any effect on suppressor T-cells. Lymphocytes are arrested in G0 or G1 phase. Etoposide: It is a semisynthetic derivative of podophyllotoxin, a plant glycoside. It is not a mitotic inhibitor, but arrests cells in the G2 phase and causes DNA breaks by affecting DNA topoisomerase II function. While the cleaving of double stranded DNA is not interfered, the subsequent resealing of the strand is prevented. It has been primarily used in testicular tumours, lung cancer, Hodgkin&;s and other lymphomas, carcinoma bladder. Alopecia, leucopenia and g.i.t. disturbances are the main toxicity. Vinblastine :It is primarily employed with other drugs in Hodgkin&;s disease and testicular carcinoma. Bone marrow depression is more prominent while neurotoxicity and alopecia are less marked than with vincristine. ESSENTIALS OF MEDICAL PHARMACOLOGY K.D.TRIPATHI SIXTH EDITION PAGE NO:823,825,837 [/INST] question: Which of the following is an anti-metabolite? | options: A: Methotrexate B: Cyclosporine C: Etoposide D: Vinblastine | answer: A </s>