Current Medicinal Chemistry - Volume 7, Issue 10, 2000

3'-Azido-2'3'-dideoxythymidine (AZT, 1, zidovudine, RetrovirTM) is used to treat patients with human immunodeficiency virus (HIV) infection. AZT, after conversion to AZT-5'-triphosphate (AZT-TP) by cellular enzymes, inhibits HIV-reverse transcriptase (HIV-RT). The major clinical limitations of AZT are due to clinical toxicities that include bone marrow suppression, hepatic abnormalities and myopathy, absolute dependence on h Read More

Cyclooxygenase is the key enzyme in the biosynthesis of prostanoids, biologically active substances that are involved in several physio- logical processes but also in pathological conditions such as inflammation. Since ten years now, it is well known that this enzyme exists under two forms: a constitutive (COX-1) and an inducible form (COX-2). Both enzymes are sensitive to inhibition by conventional nonsteroidal anti-inflammat Read More

GABA is the major inhibitory neurotransmitter in the brain and GABA re- uptake from the synaptic cleft is one important mechanism in the regulation of GABA activity. Inhibition of the re-uptake of GABA by potent and selective inhibitors of the GABA transporter enhances GABA activity. This property can be used therapeutically in for instance epilepsy or psychiatric disorders. In this paper putative structures of the GABA t Read More

A perspective is offered on the recent development of Src-homology 2 (SH2) antagonists of Src, Grb2 and ZAP-70. Inhibiting Src SH2 is believed to be a potentially attractive way of regulating bone resorption. Grb2 SH2 has been shown to be an important component of the mitogenic ras pathway; and thus might be of utility in cancer research. ZAP-70 is a tyrosine kinase that is expressed solely in T-cells and natural killer c Read More