Enzyme pro-drug therapy

K. D. Bagshawe, Antibody Directed Enzymes Revive Anti-Cancer Prodrugs Concept , Br. J. Cancer 1987, 56, 531-532 K. D. Bagshawe, Antibody-Directed Enzyme/Pro-drug Therapy (ADEPT) , Biochem. Soc. Trans. 1990, 18, 750-752. 

Antibody-directed Enzyme Pro-drug Therapy (ADEPT)... 

Francis RJ, Mather SJ, Chester K et al (2004) Radiolabelling of glycosylated MFE-23 CPG2 fusion protein (MFECPl) with Tc-99m for quantitation of tumour antibody-enzyme localisation in antibody-directed enzyme pro-drug therapy (ADEPT). Eur J Nucl Med Mol Imaging 31 1090-... 

Pro-drug (a suicide substrate) converted by xanthine oxidase, forming alloxan-thine, which inhibits the enzyme — 4> purine metabolism —uric acid. Also used in cancer chemotherapy and radiation therapy. 

As it was mentioned in the previous sections, the active principle of Fostamatinib disodium (88) is Tamatinib (92), which is formed by enzymatic hydrolysis of 88 in the intestine. As in the case of lymphoma, the effect of 88 in autoimmune diseases is related to inhibition of Spleen tyrosine kinase (Syk) by 92 [241, 242]. As Syk has the central role in transmission of activating signals within B cells, inhibition of this enzyme lowers expression of a number of pro-inflammatory cytokines and hence leads to immunosuppression [243], Fostamatinib has shown significant efficacy in the treatment of patients with rheumatoid arthritis not responding to Methotrexate (272) (a drug which is used conventionally in therapy), although a number of adverse events were observed [244], If these results are confirmed once Phase III studies are completed, it may hnd a place in the treatment of patients with rheumatoid arthritis with poor response to conventional therapy (Fig. 11). 

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