Carfilzomib

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Contents

Introduction

A selective and irreversible proteasome inhibitor used in multiple myeloma[1]. Trials are taking place with combination therapy with dexamethasone and/or lenalidomide and/or melphalan and/or panobinostat[2]. There is also interest in the combination with kinesin spindle protein inhibitors. It has enhanced inhibition of proteasome function compared to first generation proteasome inhibitors and this leads to the accumulation of proteins targeted for degradation and subsequent cellular apoptosis.

Clinical Use

Indications

Administration

IV

Clinical Issues

Less neuropathy but perhaps worse cardiac toxicity compared to other proteasome inhibitors

Contra-indications

Cautions and Interactions

Side effects

Special advice

Pharmacology

Carfilzomib is an irreversible, epoxyketone proteasome inhibitor that targets the rate limiting chymotrypsin-like activity of the proteasome subunit beta type-5 component of the 20S proteasome catalytic core of the proteasome. It is a derivative of poxomicin, a natural product isolated from actinomycetes. It forms an irreversible, selective, and highly specific adduct with the N-terminal threonine of proteasome subunit beta type-5.

References