RESEARCH: CANCER
FOLDING PROJECT #18707 PROFILE

This project aims to find new drugs that block a protein called JAK2, which is involved in some cancers like myelofibrosis. Using powerful computers and data from experiments, researchers are searching for molecules that can fit into JAK2 and stop it from working. The goal is to develop more effective and targeted treatments for these diseases. All data from this project will be made public.

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

From https://www.tandfonline.com/doi/full/10.1080/1744666X.2022.2050596: "Dysregulation of JAK signaling is a feature of many diseases.

Targeting the JAK pathway started out as a therapeutic option in the field of myeloproliferative disorders.

The JAK2 Val617Phe mutation, which results in constitutive activation of the pathway, is found in over 50% of individuals with myelofibrosis and essential thrombocythaemia, and almost 100% of patients with polycythemia vera [5,6].

Ruxolitinib, a JAK1/JAK2 inhibitor, was the first JAK inhibitor approved for clinical use to treat myelofibrosis in 2011." Starting from an AlphaFold structure of the JAK2 mutant, In these projects were are generating data to aid virtual screening efforts for new (more selective) inhibitors, as well as conducting small molecule fragment screens to find potential starting points for design efforts (which are being shared with all of you in real time, and will be summarized regularly).

This is a project run by Roivant Sciences (formerly Silicon Therapeutics) as was officially announced in this press release: https://foldingathome.org/2021/04/20/maximizing-the-impact-of-foldinghome-by-engaging-industry-collaborators/ All data is being made publicly available as soon as it is received at https://console.cloud.google.com/storage/browser/stxfah-bucket.

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JAK signaling

A biological pathway involved in cell growth and development.

JAK signaling is a crucial process in the body that controls how cells grow and respond to signals. It involves proteins called JAKs which activate other molecules to turn genes on or off. Dysregulation of this pathway can lead to various diseases, making it a target for new drugs.

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Myeloproliferative disorders

A group of cancers that affect the blood and bone marrow.

Myeloproliferative disorders are a type of cancer that affects the cells in the bone marrow responsible for producing blood. These disorders cause an overproduction of blood cells, leading to various symptoms such as fatigue, bleeding, and clotting problems.

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JAK2 Val617Phe mutation

A specific mutation in the JAK2 gene.

The JAK2 Val617Phe mutation is a common genetic alteration found in individuals with certain blood cancers like myelofibrosis and polycythemia vera. It causes the JAK2 protein to become overactive, leading to uncontrolled cell growth.

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Ruxolitinib

A medication used to treat myelofibrosis and polycythemia vera.

Ruxolitinib is a JAK inhibitor drug approved for treating certain blood cancers. It works by blocking the activity of specific proteins involved in cell growth, helping to slow down the progression of the disease.

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AlphaFold

A machine learning system that predicts protein structures.

AlphaFold is a powerful artificial intelligence program developed by DeepMind. It uses machine learning algorithms to predict the 3D structure of proteins, which is crucial for understanding their function and designing new drugs.

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Roivant Sciences

A biotechnology company focused on developing new therapies.

Roivant Sciences is a pharmaceutical research and development company that specializes in bringing innovative drugs to market. They have a portfolio of diverse projects targeting various diseases.

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Silicon Therapeutics

A former biotechnology company acquired by Roivant Sciences.

Silicon Therapeutics was a biotechnology company that focused on developing new treatments for diseases. They were acquired by Roivant Sciences in 2021.

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Folding@home

A distributed computing project that uses volunteer computer power to simulate protein folding.

Folding@home is a global research project that harnesses the processing power of millions of computers worldwide. Volunteers donate their idle computing resources to simulate protein folding, advancing our understanding of diseases and drug development.