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First\u2010in\u2010class agent, bortezomib, has demonstrated great positive therapeutic efficacy in <jats:styled-content style=\"fixed-case\">MM<\/jats:styled-content>, both in pre\u2010clinical and in clinical studies. However, despite its high efficiency, a large proportion of patients do not achieve sufficient clinical response. Therefore, the development of a second\u2010generation of proteasome inhibitors (<jats:styled-content style=\"fixed-case\">PI<\/jats:styled-content>s) with improved pharmacological properties was needed. Recently, several of these new agents have been introduced into clinics including carfilzomib, marizomib and ixazomib. Further, new orally administered second\u2010generation <jats:styled-content style=\"fixed-case\">PI<\/jats:styled-content> oprozomib is being investigated. 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