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. Author manuscript; available in PMC: 2020 Jan 1.
Published in final edited form as: Cancer Lett. 2018 Oct 9;440-441:1–10. doi: 10.1016/j.canlet.2018.10.003

Figure 6. Schematic diagram of our working model.

Figure 6.

Schematic diagram showing the different, yet complimentary mechanisms of pan-PIM kinase inhibitors and lenalidomide. Lenalidomide binds directly to CRBN, promoting the recruitment of IKZF1 and IKZF3 to CRBN and subsequent degradation of IKZF1 and IKZF3. Pan-PIM kinase inhibitors increase the expression of CRBN, resulting in enhanced recruitment of IKZF1 and IKZF3 and effective anti-myeloma activity. The combination of pan-PIM kinase inhibitors with lenalidomide provide complimentary mechanisms of action for more effective degradation of IKZF1 and IKZF3 and synergy in anti-myeloma activity.