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Serine/Threonine-Protein Kinase Inhibitors Pipeline Analysis

Serine/Threonine-Protein Kinase Inhibitors Pipeline Analysis, 2017

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Report Code: LS10818
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Serine/threonine-protein kinases (EC 2.7.11.1) are enzyme or protein that has hydroxyl (OH) group in the side chain. Phosphorylation in serine or threonine residues may cause changes in the function of the target protein. Those drugs/ligands that inhibit phosphorylating activity of these kinases are called serine/threonine protein kinases inhibitors. Serine/threonine kinase receptors are a family of transmembrane receptors containing intracellular serine/threonine kinase domains that respond to a few cytokines including the transforming growth factor beta and bone morphogenic proteins families.

According to the enzyme classification system, E.C. 2.7.11 protein-serine/threonine kinases have subclasses such as B-RAF inhibitors, mitogen-activated protein kinase inhibitors, polo-like kinase 1 inhibitors, protein-kinase-b-alpha-inhibitors, and calmodulin-dependent-protein-kinase-III-inhibitors.

The serine/threonine-protein kinase inhibitors pipeline has more than 40 drugs. In pipeline analysis, drugs are analyzed on the basis of route of administration and molecule type. The pipeline is also analyzed on the basis of monotherapy and combination therapy, and different clinical phases including phase III, phase II, phase I and preclinical stage.

Phase III

Phase III clinical trial known for the comparison of new treatments with the standard treatment in which the safety, efficacy and side effects of new intervention is compared with the already existing treatment. The phase III clinical trial takes around 2-3 years to complete and the total number of participants vary from 100-1,000. In serine/threonine protein kinase inhibitors, there are 6 drugs in phase III clinical trial. For instance, AstraZeneca plc is developing selumetinib for the treatment of differentiated thyroid cancer and second line treatment of K-Ras protein mutated non-small cell lung cancer. The orally administered drug has dual specificity for mitogen-activated protein kinase inhibitors.

Phase II

Refametinib is under development by Bayer AG as a second-line treatment for advanced biliary tract adenocarcinom and in combination with sorafenib as first line treatment in patients with Ras mutated hepatocellular carcinoma. The drug candidate is a potent, selective, allosteric inhibitor of mitogen-activated protein kinase. There are 10 drugs in phase II clinical trial. Phase II clinical trial is the second phase that answers safety, efficacy and dosing of the new intervention. It takes around 2 years to complete and between 100 – 120 patients participate in the phase II trial.

Phase I

F. Hoffmann-La Roche is developing RG7304 for the treatment of multiple myeloma and solid tumors. The drug candidate targets mitogen-activated protein kinase and inhibits its action. It is novel structure based on a coumarin skeleton. There are 16 drugs in phase I clinical trial. In phase I clinical trial, safety of the new intervention is determined. The trial takes around 1-2 years to complete and the total number of volunteers participating in the trial vary between 15 – 30.

Pre-Clinical

ASN007, an under-development drug candidate of Asana BioSciences LLC, is in preclinical stage of development for the treatment of melanoma, colon and lung cancer. Preclinical study is also known as animal study. It is done before testing a drug in people to find out the toxicity profile of the drug. Preclinical study is of two types, including in vitro and in vivo. There are 9 serine/threonine-protein kinase inhibitor drugs in preclinical trial.

Pipeline analysis provides description about the key companies which are developing serine/threonine-protein kinase inhibitors drugs. Some of the key players actively involved in the research and development are Bayer AG, AstraZeneca plc, F. Hoffmann-La Roche AG, Asana BioSciences, LLC, GlaxoSmithKline plc and Eli Lilly and Company.

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