How does methotrexate inhibit dihydrofolate reductase

After entering the cell, MTX suppresses dihydrofolate reductase 1 , thereby interferes with purine and pyrimidine synthesis 2 and 3. ADCs are a novel therapeutic approach for cancer patients. By conjugating the cytotoxic drugs with the antigen-targeting monoclonal antibodies mAbs , ADCs provide accurate targeting and drug delivery.

The carbonyl group and amino group at terminal position of MTX provide excellent functionality for modification with various linkers for subsequent antibody conjugations. Meanwhile, other MTX-antibody conjugates have also been developed for the treatment of non-small cell lung cancer and other tumors.

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For Research Use Only. For price inquiries, please feel free to contact us through the form on the left side. We will get back to you as soon as possible. Keyword Search Products. Downloads Newsletter Podcast. Methotrexate: a detailed review on drug delivery and clinical aspects. Expert Opin Drug Del. Kaltsonoudis, E. Current and future role of methotrexate in the therapeutic armamentarium for rheumatoid arthritis.

In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript. Despite the introduction of numerous biologic agents for the treatment of rheumatoid arthritis RA and other forms of inflammatory arthritis, low-dose methotrexate therapy remains the gold standard in RA therapy. Methotrexate is generally the first-line drug for the treatment of RA, psoriatic arthritis and other forms of inflammatory arthritis, and it enhances the effect of most biologic agents in RA.

Understanding the mechanism of action of methotrexate could be instructive in the appropriate use of the drug and in the design of new regimens for the treatment of RA. Methotrexate polyglutamates inhibit aminoimidazolecarboxamide ribonucleotide AICAR transformylase ATIC , leading to intracellular accumulation of AICAR and increased adenosine release; adenosine binds to cell surface receptors and suppresses many inflammatory and immune reactions. Methotrexate inhibits dihydrofolate reductase, preventing the reduction of dihydrobiopterin BH2 to tetrahydrobiopterin BH4 , leading to nitric oxide synthase uncoupling and increased sensitivity of T cells to apoptosis, thereby diminishing immune responses.

Methotrexate increases the expression of long intergenic non-coding RNA p21 lincRNA-p21 , which is a multifunction long non-coding RNA that regulates, both directly and indirectly, a variety of critical immune and inflammatory processes. By modulating cell-specific signalling pathways, methotrexate inhibits important pro-inflammatory properties of major cell lineages involved in rheumatoid arthritis pathogenesis, including T cells, macrophages, endothelial cells and fibroblast-like synoviocytes.

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