5/5-5/6-BISARYL COMPOUNDS AS TRANSFORMING GROWTH FACTOR-β ACTIVATED KINASE, TAK1, INHIBITORS

Protein phosphorylation plays a crucial role in cellular signaling pathways. A disruption of tightly regulated phosphorylation can often result in numerous diseases, including inflammatory disorders, cancer, and autoimmune diseases. As a result, targeting disease-associated kinases with specific inhibitors has emerged as an appealing strategy for drug development. While there are over 500 protein kinases in the cell, only a handful (less than 10%) have been successfully drugged in the clinic Transforming growth factor-β-activated kinase 1 (TAK1), a serine/threonine kinase, plays pathological roles in cancer and inflammatory diseases, but a clinical candidate specifically developed against this kinase is lacking.

Researchers at Purdue University have developed 5/5-5/6-bisaryl compounds that are inhibitors of transforming growth factor-β activated kinase (TAK1) which can be used to treat cancer and inflammatory disease. Moreover, the compound can be administered orally, intravenously, intramuscularly, dermally, rectally, nasally, otically, or ocularly.

Technology Validation:

At sub-micromolar concentrations, such as 200 nM, the compounds were able to inhibit the proliferation of MPC-11. Compounds were able to inhibit the proliferation of another MM line, RPMI8226, in a mouse model. The chemical compound is currently being tested in different cancer models. In sum, in-vivo efficacy and oral bioavailability have been demonstrated.

Advantages:

-Orally bioavailable

-These are highly selective and potent TAK1 inhibitors

Applications:

-Cancer

-Arthritis

TRL: Pharmaceuticals

Intellectual Property:

Keywords: acute lymphoblastic leukemia, acute myeloid leukemia, Biotechnology, Cancer, FLT3, Kinase inhibitor, Pharmaceuticals, TAK1