Treatment of Myeloma With Immunomodulatory Drugs

As part of the application for marketing approval, the FDA requires a description of the mechanism of action (MOA) of a drug candidate. I’d wondered about the reliability of some of the proposed MOAs.

A paper by Chung and colleagues at the University of California at San Francisco describes how immunomodulatory drugs (IMiDs) can bind to cereblon and Ikaros to bring the latter two together in the cytoplasm.1 This is part of a cell signaling mechanism. The experiment involves modifying the cereblon and Ikaros with green fluorescent protein. The GFP uniformly colors the cell dimly, but adds a tad of IMiDs. Then, the complex forms and the fluorescence increases dramatically, showing that the complex is located in microdrops inside the cell.

The paper is supported by a short video that explains how IMiDs can be used to treat myeloma.2 Look at it, and you’ll be a believer, too.

References

  1. Chung, C.-I.; Zhang, Q. et. al. Dynamic imaging of small molecule induced protein--protein interactions in living cells with a flurophore phase transition approach. Anal. Chem. Nov. 15, 2018; doi: 10.1021/acs.analchem.8b03476.
  2. https://www.youtube.com/watch?v=9md8rWPGJ28&feature=youtube

Robert L. Stevenson, Ph.D., is Editor Emeritus, American Laboratory/Labcompare; e-mail: [email protected]

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