NPI-0052 another update

Chauhan D, Hideshima T, Anderson KC

Department of Medical Oncology, Harvard Medical School, Dana Farber Cancer Institute, The Jerome Lipper Multiple Myeloma Center, Boston, MA 02115, USA.

Proteasome inhibitor Bortezomib/Velcade has emerged as an effective anticancer therapy for the treatment of relapsed and/or refractory multiple myeloma (MM), but prolonged treatment can be associated with toxicity and development of drug resistance. In this review, we discuss the recent discovery of a novel proteasome inhibitor, NPI-0052, that is distinct from Bortezomib in its chemical structure, mechanisms of action, and effects on proteasomal activities; most importantly, it overcomes resistance to conventional and Bortezomib therapies. In vivo studies using human MM xenografts shows that NPI-0052 is well tolerated, prolongs survival, and reduces tumour recurrence. These preclinical studies provided the basis for Phase-I clinical trial of NPI-0052 in relapsed/refractory MM patients.British Journal of Cancer (2006) 95, 961-965. doi:10.1038/sj.bjc.6603406 www.bjcancer.com.

PMID: 17047643 [PubMed - in process]