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Researchers Design and Develop New Class of Molecules to Halt Tumors

Researchers at Stevens Institute of Technology and colleagues have designed and developed a new class of molecules that use a never-before-known mechanism that may halt or destroy breast cancer tumors.

This mechanism can be used for patients with drug-resistant or dangerously metastatic stages of the disease.

The molecule developed by the scientists could potentially add to the arsenal of drugs actively being developed to degrade or inhibit estrogen receptors, proteins inside cells that have been proven to be the single most important target in breast cancer therapy.

The unique benefit of these compounds is that they contain fundamentally different type of structures.

Manu breast cancer tumors become resistant to these drugs, necessitating more toxic chemotherapies to prevent the cancer from relapsing and progressing.
SERDs are also difficult to formulate into pills, and treatment requires large, painful injections directly into a patient's muscles.

Scientists took a core substance already known to act as a good ‘homing device’ for estrogen receptors and attached it to a series of experimental side-chain compounds known as degrons.
Once the homing device attached to the estrogen receptor, the degrons degraded it by way of hijacking a cancer cell's protein-disposal machinery and routing it to the receptor (a protein).

They synthesised several variations of the novel compound, each taking weeks to months to design and produce.

Researchers then tested more than a dozen of them to see how they interacted with the cancer cells' estrogen receptors.

The new compounds were found to deliver a one-two punch, not only degrading estrogen receptors and inhibiting the signals that cue the cell to grow, but also blocking the hormone estrogen from binding to it.

The compounds also strongly inhibited the growth and proliferation of breast cancer cells. This is a novel molecular structure, and several analogs produced excellent early activity.

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