Compound E61 Overcomes Proteasome Inhibitor Resistance in Multiple Myeloma


Technology: Proteasome inhibitors (PIs) such as bortezomib/Velcade and carfilzomib/Kyprolis are approved for the treatment of the blood cancer multiple myeloma (MM). While PIs may initially be effective, all patients develop resistance and their disease progresses, marking the incurable nature of this disease. Through an MM drug discovery and high throughput drug-screening (HTS) program at MUSC, researchers have identified a small molecule drug that not only enhances the activity of PIs but also restores sensitivity in MM cells that have acquired resistance. This developmental small molecule drug (named “E61”), in addition to acting synergistically with PIs, has demonstrated selective anti-MM activity as a single agent, killing MM cells with >10 times more potency than normal cell types. E61 is effective in an aggressive mouse model of PI refractory MM in which it significantly reduced MM tumor burden and prolonged animal survival. E61 is a novel small molecule that has structural similarity to a natural product and is well tolerated in mice.

The technology category is a therapeutic small molecule for the treatment of treatment refractory MM. E61 will be used to treat late stage MM patients as a single agent and may be best utilized in combination with Velcade and next generation PIs due to synergy with these agents.




Overview: PIs are cornerstone agents in the treatment of Multiple Myeloma (MM). Despite the initial effectiveness of PIs, resistance is inescapable and represents a significant obstacle to sustained and durable responses in patients. A need exists for new, targeted strategies that are effective in PI refractory MM.


The market for MM is predicted to top $7B by 2021. PIs will account for a large share of this market, and therefore, a companion therapeutic such as this represents a significant commercial opportunity.


Applications: Inhibition of tumor growth.

Advantages: Designed for treatment resistant patients, enhances the activity of standard of care agents, natural product with minimal toxicity in animals

Key Words: Multiple myeloma, cancer, proteasome inhibitor, Velcade, bortezomib, drug resistance, small molecule


Inventors: Nathan Dolloff, Reeder Robinson

Patent Status:   PCT/US2017/022665

MUSC-FRD Technology ID: P1607




Patent Information:
For Information, Contact:
Troy Huth
Sr Licensing Manager
MUSC Foundation for Research Development
Nathan Dolloff
Reeder Robinson
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