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Our Science

A class of targeted drugs known as tyrosine kinase inhibitors (TKIs) has played a transformative role in modern cancer treatment. With their ability to interrupt kinase signaling that leads to unchecked cell growth and tumor progression, more than 30 have been approved since the late 1990s.

Tumors invariably become resistant to kinase inhibitors, often within one to two years.

Most kinase inhibitor molecules share a similar oversized shape and use comparable binding mechanisms. Thus, resistance to one often means resistance to all.

Our Approach

Turning Point Therapeutics exists to give patients a better option.

We have created a new generation of therapies that are different from conventional kinase inhibitors. Our compact molecules are potentially more potent and selective medicines that also hold promise to prevent and overcome resistance.

Better Fit

Smaller, more compact molecules fit directly in the ATP binding pocket to destroy cancer cells.

Avoid Resistance

Rigid 3-D structure reduces interference and potentially bypasses mutations that are responsible for resistance to early-generation kinase inhibitors.

Less Toxicity

Smaller structure is potentially less prone to common toxicity issues found in the TKI drug class.

Addressing Resistance

Cancers evolve, or mutate, to evade the effects of a drug. When confronted with kinase inhibitors, two types of mutations most commonly emerge: solvent-front mutations and gatekeeper mutations. Both are “acquired,” meaning they emerge only after a tumor is exposed to the drug.

Most of the currently approved or investigational ROS1, ALK and TRK kinase inhibitors have an extra chemical group that extends to the solvent-front area of the kinase. As a result, these drugs are vulnerable to solvent-front mutations.

We seek to overcome resistance by design.

Our therapies are designed differently. They are structurally compact, with a low molecular weight and a rigid three-dimensional structure that binds neatly inside an area of the cancer cell known as the “ATP” pocket. ATP is a critical molecule for cell energy and growth. By binding completely inside the ATP pocket, our TKIs can bind to solvent-front mutations that evade conventional TKIs.

Publications

Scientific Presentations

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