Natural Products in Clinical Trials

Natural Products in Clinical Trials

Natural products continue to play a key role in drug development. A recent analysis of the drug market in the developed world revealed that 40% of total clinically approved drugs were either ...
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Natural Product Derived Drugs for Immunological and Inflammatory Diseases

Pp. 31-78 (48)

Narayana Subbiah Hari Narayana Moorthy, Vijayakumari Pratheepa and Elangovan Manivannan

Abstract

Natural products derived drugs are usually associated with secondary metabolites, produced by different natural sources including plants, microorganisms, insects, animals, marine sources, etc, which can be used as a drug for the treatment of various diseases including, cancer, infectious disease, cardiovascular diseases, carbohydrate and cholesterol mediated diseases, inflammatory, neurological and immunological diseases. In this chapter, we describe the natural products derived drugs that are under clinical trials (Phase studies) for the treatment of inflammatory and immunological diseases. These diseases are named as immune-mediated inflammatory disorders (autoimmune disorders), which are associated with many other disorders. Voclosporin is under Phase IIb trials for the prevention and treatment of kidney graft rejection. KRP-203 is a fingolimod analogue undergoing Phase study for transplantation, autoimmune diseases and inflammatory bowel diseases. PG490-88 (14-succinyl triptolide sodium salt) is a semisynthetic analogue of triptolide, isolated from Tripterygium wilfordii, which exhibits anti-autoimmune and anti-inflammatory properties. Didemnin B (first compound obtained from the sea that directly entered into human clinical trials against cancer) feasibly modulates the activity of FK-506 binding proteins as part of its immunomodulatory process and thus leads to cell death via apoptosis. Didemnin B has been withdrawn subsequently due to its toxic and immunosuppressive effects. Some natural compounds such as manoalide and luffariellolide (with anti-inflammatory effects) are in clinical studies. Inflazyme Pharmaceuticals Ltd, Canada and Avantis Pharma Inc, Germany has reported some derivatives of the IPL576 series for asthma and other diseases. The derivative (IPL550,260) possessed anti-inflammatory activity and is currently in clinical studies. This chapter provides knowledge to the readers on the recent development on the clinical trials drugs derived from natural products for these diseases.

Keywords:

Analgesic, Anti-inflammatory, Clinical trials, Cyclosporine, Flavonoids, Immunomodulators, Immunosuppresants, Multiple sclerosis, Natural products, Phase studies, Psoriasis.

Affiliation:

Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade do Porto, s/n, Rua do Campo Alegre, 4169-007 Porto, Portugal.