Therapeutic potential

Therapeutic potential of cidofouvir, (S)-l-[3-hydroxy-2-(phosphonomethoxy) propyl]cytosine (HPMPC) for the treatment of DNA virus infections 98CCC480. 

Apart from these two Vertex compounds, only one other caspase inhibitor, BDN-6556, has been used in clinical trials. This compound belongs to the class of oxamyl dipeptides and was originally developed by Idun Pharmaceuticals (taken over by Pfizer). It is the only pan-caspase inhibitor that has been evaluated in humans. BDN-6556 displays inhibitory activity against all tested human caspases. It is also an irreversible, caspase-specific inhibitor that does not inhibit other major classes of proteases, or other enzymes or receptors. The therapeutic potential of BDN-6556 was first evaluated in several animal models of liver disease because numerous publications suggested that apoptosis contributes substantially to the development of some hepatic diseases, such as alcoholic hepatitis, hepatitis B and C (HBV, HCV), non-alcoholic steato-hepatitis (NASH), and ischemia/reperfusion injury associated with liver transplant. Accordingly, BDN-6556 was tested in a phase I study. The drug was safe and... 

Cholecystokinin (CCK) is produced in the intestine and the brain. It appears to be an important mediator of anxiety. It also stimulates vasopressin secretion and slows gastric emptying. In addition, it is an important humoral satiety signal (appetite control). Various antagonists have been developed and are currently being investigated with regard to their therapeutic potential. 

Krieg AM (2006) Therapeutic potential of Toll-like receptor 9 activation. Nat Rev Drag Discov 5(6) 471-484. 

Melanocortin peptides have been proposed as potent modulators of many pathologies including inflammatory (asthma, arthritis) and cardiovascular disease. They have been shown to be directed against resident cells within tissue such as macrophages, endothelial cells and also circulating leukocytes (neutrophils and lymphocytes). Therefore harnessing their therapeutic potential could lead to the development of novel therapeutics. 

Youdim MB, Edmondson D, Tipton KF (2006) The therapeutic potential of monoamine oxidase inhibitors. Nat Rev Neurosci 7(4) 295-309... 

A number of inhibitors directed towards the active site of PKC have been developed [4]. Many of these have therapeutic potential and some are in clinical trials. The drug enzastaurin (LY317615) shows selectivity towards inhibiting PKC 3 and is currently in clinical trials for cancer. This drug has particular potential as a treatment for colon cancer because of the specific role ofPKC (311 in this disease (see above). A separate PKC (3 inhibitor, ruboxistaurin (LY333531) has been developed as a drug to treat the microvasculature complications of diabetes hyperactivation of both PKC (311 and PKC (31 contribute to diabetic retinopathy and microvasculature complications. 

There is increasing interest in the therapeutic potential of purinergic compounds in relation to both PI and P2 receptors [4]. A number of purine-related compounds have been patented. 

Burnstock, G (2006) Pathophysiology and therapeutic potential of purinergic signalling. Pharmacol Rev 58 58-86... 

For patients with leukemia, the transfer of siRNA-based strategies into clinical applicability will certainly be both frustrating and time-consuming and many hurdles still have to be overcome in order to realize the therapeutic potential of siRNAs. Efficient delivery of siRNA into the leukemic stem cell and their unknown influence of the patient s immune system are the most challenging issues that need to be addressed. 

Evgenov OV, Pacher P, Schmidt PM et al (2006) NO-independent stimulators and activators of soluble guany-late cyclase discovery and therapeutic potential. Nat Rev Drug Discov 5 755—768... 

We have gained considerable insight into the therapeutic potential of this protein through the use of TGF-(3 antagonists and transgenic mice with defective TGF-(3 signaling and we have evaluated the potential toxicity of TGF-(3 modulation and its overall efficacy in treating cancer. FC Soluble Type II Receptor... 

Nanaomycin A 103 and deoxyfrenolicin 108 are members of a group of naphthoquinone antibiotics based on the isochroman skeleton. The therapeutic potential of these natural products has attracted considerable attention, and different approaches towards their synthesis have been reported [65,66]. The key step in the total synthesis of racemic nanaomycin A 103 is the chemo-and regioselective benzannulation reaction of carbene complex 101 and allylacety-lene 100 to give allyl-substituted naphthoquinone 102 after oxidative workup in 52% yield [65] (Scheme 47). The allyl functionality is crucial for a subsequent intramolecular alkoxycarbonylation to build up the isochroman structure. However, modest yields and the long sequence required to introduce the... 

Baker D, Pryce G, Giovannoni G, et al The therapeutic potential of cannabis. Lancet Neurol 2 291-298, 2003... 

Thiophenes continue to play a major role in commercial applications as well as basic research. In addition to its aromatic properties that make it a useful replacement for benzene in small molecule syntheses, thiophene is a key element in superconductors, photochemical switches and polymers. The presence of sulfur-containing components (especially thiophene and benzothiophene) in crude petroleum requires development of new catalysts to promote their removal (hydrodesulfurization, HDS) at refineries. Interspersed with these commercial applications, basic research on thiophene has continued to study its role in electrocyclic reactions, newer routes for its formation and substitution and new derivatives of therapeutic potential. New reports of selenophenes and tellurophenes continue to be modest in number. 

In vivo reproducible results can only be achieved if the liposome-drug or -antigen combinations are thoroughly characterized upon preparation in terms of their physical and chemical properties and, besides, if the stability during storage is ensured. In this chapter both the pharmaceutical (preparation, characterization, and stability) aspects and the therapeutic potentials and limitations of drug and antigen delivery with liposomes will be discussed. 

Courtney M., Jallat S., Tessier L-H., Benavente A., Crystal R.G. Lecocq J-P. (1985) Synthesis in E. coli of alpha,-antitrypsin variants of therapeutic potential for emphysema and thrombosis. Nature, 313, 149-151. 

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