Chemical and Pharmaceutical Bulletin
Online ISSN : 1347-5223
Print ISSN : 0009-2363
ISSN-L : 0009-2363
Current Topics: Reviews
Development of a Potent Protein Degrader against Oncogenic BCR-ABL Protein
Norihito ShibataNobumichi OhokaTakayuki HattoriMikihiko Naito
Author information
JOURNALS FREE ACCESS FULL-TEXT HTML

2019 Volume 67 Issue 3 Pages 165-172

Details
Abstract

Chromosomal translocation occurs in some cancer cells, resulting in the expression of aberrant oncogenic fusion proteins that include BCR-ABL in chronic myelogenous leukemia (CML). Inhibitors of ABL tyrosine kinase, such as imatinib and dasatinib, exhibit remarkable therapeutic effects, although emergence of drug resistance hampers the therapy during long-term treatment. An alternative approach to treat CML is to downregulate expression of the BCR-ABL protein. Recently, we have devised a protein knockdown system by hybrid molecules named Specific and Nongenetic inhibitor of apoptosis protein [IAP]-dependent Protein Erasers (SNIPER). This system is designed to induce IAP-mediated ubiquitylation and proteasomal degradation of target proteins. In this review, we describe the development of SNIPER against BCR-ABL, and discuss the features and prospect for treatment of CML.

Graphical Abstract Fullsize Image
Information related to the author
© 2019 The Pharmaceutical Society of Japan
Previous article Next article
feedback
Top