Purushottamachar Puranik - Retinoic acid metabolism blocking agents (RAMBAs) for treatment of cancer and dermatological diseases.

Version 1

      Publication Details (including relevant citation   information):

      Bioorg Med Chem. 2006   Jul 1;14(13):4323-40. Epub 2006 Mar 10.

      Abstract:

      The naturally occurring retinoids and their synthetic analogs   play a key role in differentiation, proliferation, and apoptosis,   and their use/potential in oncology, dermatology and a variety of   diseases are well documented. This review focuses on the role of   all-trans-retinoic acid (ATRA), the principal endogenous   metabolite of vitamin A (retinol) and its metabolism in oncology   and dermatology. ATRA has been used successfully in   differentiated therapy of acute promyelocytic leukemia, skin   cancer, Kaposi's sarcoma, and cutaneous T-cell lymphoma, and also   in the treatment of acne and psoriasis. However, its usefulness   is limited by the rapid emergence of acquired ATRA resistance   involving multifactoral mechanisms. A key mechanism of resistance   involves ATRA-induced catabolism of ATRA. Thus, a novel strategy   to overcome the limitation associated with exogenous ATRA therapy   has been to modulate and/or increase the levels of endogenous   ATRA by inhibiting the cytochrome P450-dependent   ATRA-4-hydroxylase enzymes (particularly CYP26s) responsible for   ATRA metabolism. These inhibitors are also referred to as   retinoic acid metabolism blocking agents (RAMBAs). This review   highlights development in the design, synthesis, and evaluation   of RAMBAs. Major emphasis is given to liarozole, the most studied   and only RAMBA in clinical use and also the new RAMBAs in   development and with clinical potential.

     
       
          PMID: 16530416    
     

      Address (URL): http://www.ncbi.nlm.nih.gov/pubmed/16530416