Inhibitors as Drugs

Stromelysin 1 MMP 3 Nonfibrillar collagens Laminins Fibronectins Arthritis 

Matrilysin MMP 7 Nonfibrillar collagens Laminins Fibronectins Inflammation 

Batimastat (BB-94) (4-(A -hydroxyamino)-2(R)-isobutyl-3(S)-[2-thie-nylthiomethyl) succinyl]-L-phenylalanine-iV-methylamide) is a broad-spectrum inhibitor with nanomolar activity against the MMPs and is in phase II clinical trial for treatment of breast and ovarian cancer 

Inhibitors of human neutrophil collagenase and human stromelysin have been designed (577) which are based on previous classes of MMP inhibitors, iV-carboxyalkyl peptides (578, 579), and peptide-based hy-droxamic acids (117) (580, 581). The -CH3 and 2-phenylethyl groups are important for inhibition of MMP-3. The X-ray crystal structure of MMP-3 with bound 117 shows that the inhibitor chelates Zn(II) 

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R. F. Pratt in M. Sandler and H. J. Smith, eds.. Design ofEn me Inhibitors as Drugs, Oxford University Press, New York, 1989, pp. 178—205. 

The requirements of protease inhibitors as drugs in terms of potency, pharmacokinetics, and toxicity will vary depending on the nature of the infection and the goals of therapy. At one extreme is treatment of HlV-1, a chroific infection that requires life-long therapy and full suppression of viral replication. At the other extreme is the treatment of human rhinovirus (i.e., the cold virus), where short-term treatment to blunt viremia will likely be sufficient to reduce the unwanted symptoms of a cold. In all cases, viral proteases represent very attractive targets with familiar mechanisms of catalysis that frequently allow for the design of transition state analogs and with distinct specificities from host proteases. 

Pratt, R. F. P-Lactamases inhibitors. In The Design of Enzyme Inhibitors as Drugs Sandler, M. Smith, H. J., Eds. Oxford University Press Oxford, UK 1989 pp 596-619. 

G. H. Hitchings and B. Roth, Enzyme Inhibitors as Drugs, M. Sandler, ed. University... 

XIV. Metalloenzyme Inhibitors as Drugs XV. Conclusion and Outlook Acknowledgments References... 

J. C. Schwartz, Enkephalinase Inhibitors as Drugs , in Design of Enzyme Inhibitors as Drugs , Eds. M. Sandler, H. J. Smith, Oxford University Press, Oxford, 1989, p. 206-226. 

WrUiams DH, Mitchell T. Latest developments in crystallography and structure-based design of protein kinase inhibitors as drug candidates. Curr Opin Pharmacol 2002 2 567-73. 

Proteinase inhibitors. In Barrett AJ, Salvesen G, eds. Research Monographs in Cell and Tissue Physiology. Vol 12. New York Elsevier, 1986. Design of Enzyme Inhibitors as Drugs. Sandler M,... 

Sandler, M., ed. (1980) Enzyme Inhibitors as Drugs, Univ. Park Press, Baltimore, Maryland... 

Horl WH. Proteinases potential role in health and disease. In Sandler M, Smith HJ, editors. Design of Enzyme Inhibitors as Drugs. Oxford Oxford University Press, 1989 573-581. 

John, R. A. Enzyme-Induced Inactivation of Pyridoxal Phosphate-Dependent Enzymes Approaches to the design of specific inhibitors, in Enzyme Inhibitors as Drugs, (ed.) Sandler, M p. 73, London, Macmillan Press 1980... 

Use of fatty acid synthase inhibitors as drugs Section 22.4.9 Effects of aspirin on signaling pathways Section 22.6.2 Cervical cancer and ubiquitin Section 23.2.1 Protein degradation and the immune response Section 23.2.3 Inherited defects of the urea cycle (hyperammonemia) Section 23.4.4... 

Repke KRH, Schonfeld W, Welland J, Megges R, Hache A (1989) In Sandler M, Smith HI (eds) Design of enzyme inhibitors as drugs. Oxford University Press, Oxford, p 435... 

Use of fatty acid synthase inhibitors as drugs (p. 640) Effects of aspirin on signaling pathways (p. 644)... 

Nucleoside Analogue HIV Reverse Transcriptase Inhibitors as Drugs for the Treatment of HIV and Hepatitis B Zidovudine, Didanosine, Stavudine, Lamivudine, Abacavir, Emtricitabine and Entecavir... 

Non-Nucleoside Reverse Transcriptase Inhibitor as Drugs for the Treatment of HIV Efavirenz, Nevirapine, Delavirdine, Apricitabine and Etravirine... 

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