JAK Inhibitors-Pipeline Insights

• Janus kinase (JAK) inhibitors block the Janus kinase activator enzymes thereby interrupting signaling pathway. JAK inhibitors target the process leading to the production of the damaged DNA that is playing the major role in producing cancerous cells.
• Many signal transduction pathways have to be done by JAK activity to induce normal signaling. The abnormal variation in JAKs activity will lead to a diseased condition.
• For example, overactivation of JAK will lead to tumorigenesis whereas loss of JAK will lead to severe combined immunodeficiency. Janus Kinases family includes JAK 1, JAK 2, JAK 3 and also a group of cytoplasmic non-receptor Tyrosine kinases (NRTKs).
• The JAKs present on the surface of cells got associated with cytokine receptor. JAK tyrosine kinase family is firstly associated with signal transduction coming from extracellular ligands that will often interact with transmembrane receptors.
• Different ones of JAK tyrosine kinase are the critical elements in mediating signaling processes like an expression of genes that are involved in the process of proliferation, apoptosis, migration, and differentiation.
• They play an essential role in immune defense action as many signaling events involved in innate and adaptive immunity is mediated by JAKs. They are also associated with cell growth, survival, development, and differentiation of immune cells. Thus mutation in JAKs is leading to the immunodeficiency disorders.
• Janus kinase inhibitors have emerged as one of the latest potential candidate and growth frontier by many scientific researchers involved in the research and development of cancer drugs and targeted therapies.
• The available JAK inhibitors are most highly focused on treating rare hematological malignancies such as myelofibrosis, primary thrombocythemia, and Polycythemia Vera.
• However, the continuous efforts of the researchers have led to the detection of the JAK pathway role in a wide range of solid tumors including lung cancer, prostate cancer, pancreatic cancer, breast cancer, ovarian cancer, colorectal cancer, gastrointestinal cancers.
• Currently, there is only one Janus kinase inhibitors drug that is commercially available in the market by approving Ruxolitinib.
• Although this drug is approved for the treatment of rare hematological malignancies occurrence rate of these cancers has been increasing in the past years.
• Further, the lack of effective treatment for these cancers and higher survival rates of the patients after treatment with Ruxolitinib has aided the commercial success of Ruxolitinib. And 27 drugs are found to be in various clinical development phases.
• Most of the drugs are in Preclinical phase followed by the Phase-II clinical trials. There are six drugs in Phase III clinical trial including baricitinib for the treatment of rheumatoid arthritis.
• Itacitinib has reached into Phase II clinical trial phase for the treatment of primary myelofibrosis, non-small cell lung cancer, post-polycythemia vera myelofibrosis, and refractory Hodgkin lymphoma. CTP-543, a Phase I drug candidate is developing for alopecia area. It is an inhibitor of JAK1 and JAK2 that is involved in autoimmune disease. A pre-clinical drug candidate ATI-50001 is preparing for the treatment of alopecia. The Promising Candidates in the Clinical Pipeline includes Momelotinib, Lestaurtinib, Pacritinib.
• More than 5 JAK inhibitors are expected to enter into the market in the next decade. The development of JAK inhibitors has been so impressive and fastest in the past five years and thus expecting a tremendous economic success of this class of drugs in the nearby future. Furthermore, the enormous commercial success of the Ruxolitinib JAK inhibitor for myeloproliferative disorders further accelerated the development of more JAK inhibitors in the market.
• Advances in research and technology will add to the development of JAK inhibitors. The development of more JAK inhibitors will not only provides benefits to the therapeutic cancer market but will also add a better life from cancers to the patients.