Ibrutinib

The API expertise for producing Ibrutinib is Synthetic Organic Chemistry.

For more information about Synthetic Organic Chemistry please click here

Ibrutinib is an orally administered anticancer drug for the treatment of mantle cell lymphoma (MCL), chronic lymphocytic leukemia (CLL) and Waldenstr?m's macroglobulinemia (WM ' also known as lymphoplasmacytic lymphoma).

These diseases are called B-cell malignancies. A B-cell is a type of white blood cell that takes part in immune activity in organs such as the spleen and lymph nodes. Mutations in certain genes cause B-cells to become malignant. Ibrutinib has been reported to promote self-destruction (apoptosis) of malignant B-cells, inhibit their proliferation, and also prevent them from responding to survival stimuli provided by the tumor microenvironment.

In MCL and CLL, ibrutinib can be used in patients who have received at least one prior therapy without success. For the treatment of WM or CLL with 17p deletion (a certain mutation) there is no such requirement. 

Under the trade name Imbruvica, ibrutinib was approved by the FDA in 2013 for the treatment of MCL, and in 2014 for the treatment of CLL. In 2015, ibrutinib was approved for treatment of WM. It is produced through multi-step chemical synthesis.

The enzyme Bruton tyrosine kinase (BTK) is a critical factor in B-cell signaling, which in turn is crucial for the survival and progression of B-cell malignancies. BTK also plays a role in cell migration and responsiveness to protective factors.

Ibrutinib irreversibly inhibits BTK activity, thus preventing B-cell-mediated signaling. A small molecule, ibrutinib is able to form a covalent bond with a cysteine residue at the active site (the ATP binding domain) of BTK. This ultimately blocks the growth and spread of B cells, and induces apoptosis.

In patients with recurrent B-cell lymphoma, more than 90% occupancy of the BTK active site in peripheral blood mononuclear cells was observed up to 24 hours post dose.