RESEARCH: CANCER
FOLDING PROJECT #16495 PROFILE

This project studies how certain drugs block RIPK2, a protein involved in cancer growth. By looking at the structure of RIPK2 with and without these drugs, scientists hope to understand how the drugs work and better design new cancer treatments.

Note: This TLDR is a simplication and may not be 100% accurate.

Kinases are a major target for a variety of cancer therapies, but their mechanism of action is relatively unknown at a detailed atomic level, preventing us from understanding and optimizing known inhibitors.

One example is the Serine/Threonine Kinase RIPK2.

RIPK2 inhibition is useful for cancer targeting as it prevents RIPK2 from binding a protein partner named XIAP.

In fact, there are already 3 known inhibitors that bind to RIPK2 and prevent RIPK2-XIAP binding! However, it remains difficult to optimize these ligands for clinical purposes because we do not understand how any of these three inhibitors actually act on RIPK2 to prevent XIAP binding behavior.

These four projects are simulating RIPK2 by itself and bound to each of the three inhibitors, with the hope that this will reveal a more detailed mechanism of how each inhibitor works to prevent XIAP binding.

As a bonus, this will help reveal how RIPK2 *binds* XIAP (also unknown)! In this set of projects we are studying the following systems: 16466 – RIPK2 16467 – RIPK2:CSLP43 inhibitor-bound complex 16468 – RIPK2:CSLP48 inhibitor-bound complex 16469 – RIPK2:GSK583 inhibitor-bound complex 16470 – RIPK2:WEHI-345 inhibitor-bound complex 16471 – RIPK2:BI inhibitor-bound complex 16488 – RIPK2:BI inhibitor-bound complex (alt configuration) 16489 – RIPK2:BI inhibitor-bound complex (alt configuration 2) 16490 – RIPK2:NVS inhibitor-bound complex 16491 – RIPK2 apo from the GSK bound structure 16492 – RIPK2 apo fro the BI bound structure 16493 – RIPK2 apo from a Gefitinib bound structure 16494 – RIPK2 apo from a Novartis-produced inhibitor 16495 – RIPK2:Gefitinib complex 16496 – RIPK2:Novartis inhibitor structure.

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Kinases

Enzymes that add phosphate groups to molecules.

Kinases are a type of enzyme that play a crucial role in various cellular processes by adding phosphate groups to other molecules. They are involved in signal transduction, cell growth, and metabolism. Aberrant kinase activity is often implicated in diseases like cancer.

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RIPK2

Receptor-Interacting Protein Kinase 2

RIPK2 is a protein kinase involved in the innate immune response. It plays a role in cell death signaling and inflammation. Inhibition of RIPK2 has been explored as a potential therapeutic strategy for cancer and inflammatory diseases.

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XIAP

X-linked Inhibitor of Apoptosis Protein

XIAP is a protein that inhibits apoptosis, or programmed cell death. It plays a role in cancer development and survival by preventing the elimination of cancerous cells. Targeting XIAP has emerged as a potential therapeutic approach for cancer treatment.

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Inhibitors

Substances that block or reduce the activity of a target molecule.

Inhibitors are molecules designed to interfere with the function of specific biological targets, such as enzymes or proteins. They are widely used in drug development to treat various diseases by blocking the action of disease-causing molecules.

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Ligands

Molecules that bind to a specific target molecule.

Ligands are molecules that have a high affinity for a specific target site, such as a receptor or enzyme. They play crucial roles in cellular signaling and drug interactions. In drug discovery, ligands are essential for identifying potential therapeutic agents.

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GSK583

A specific inhibitor of RIPK2.

GSK583 is a small molecule inhibitor that specifically targets the RIPK2 protein kinase. It has shown promising results in preclinical studies for treating cancer and inflammatory diseases.

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WEHI-345

A specific inhibitor of RIPK2.

WEHI-345 is another small molecule inhibitor that targets the RIPK2 protein kinase. It has been investigated for its potential therapeutic applications in cancer and autoimmune diseases.

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CSLP43

A small molecule inhibitor of RIPK2.

CSLP43 is a specific inhibitor that targets the RIPK2 protein kinase. Its mechanism of action and therapeutic potential are being further investigated.

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Gefitinib

A tyrosine kinase inhibitor used in the treatment of lung cancer.

Gefitinib is a targeted therapy drug that inhibits the EGFR (epidermal growth factor receptor) tyrosine kinase. It is effective in treating certain types of non-small cell lung cancer.