Quizartinib (AC220) is a small molecule

receptor tyrosine kinase Receptor tyrosine kinases (RTKs) are the high- affinity cell surface receptors for many polypeptide growth factors, cytokines, and hormones. Of the 90 unique tyrosine kinase genes identified in the human genome, 58 encode receptor tyrosine ...

inhibitor, originally from Ambit Biosciences and later acquired by

Daiichi Sankyo is a global pharmaceutical company and the second-largest pharmaceutical company in Japan. It achieved JPY 981.8 billion in revenue in 2019. The company owns the American biotechnology company Plexxikon, American pharmaceutical company American ...

, that is currently under development for the treatment of

acute myeloid leukaemia Acute myeloid leukemia (AML) is a cancer of the myeloid line of blood cells, characterized by the rapid growth of abnormal cells that build up in the bone marrow and blood and interfere with normal blood cell production. Symptoms may include ...

. Quizartinib is sold under the brand name Vanflyta in Japan. Its molecular target is

FLT3 Cluster of differentiation antigen 135 (CD135) also known as fms like tyrosine kinase 3 (FLT-3), receptor-type tyrosine-protein kinase FLT3, or fetal liver kinase-2 (Flk2) is a protein that in humans is encoded by the ''FLT3'' gene. FLT3 is a cyto ...

, also known as CD135 which is a

proto-oncogene An oncogene is a gene that has the potential to cause cancer. In tumor cells, these genes are often mutated, or expressed at high levels.

. Flt3 mutations are among the most common mutations in

due to

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of Flt3. The presence of this mutation is a marker of adverse outcome. __TOC__

Mechanism

Specifically, quizartinib selectively inhibits class III receptor tyrosine kinases, including FMS-related tyrosine kinase 3 (

/STK1), colony-stimulating factor 1 receptor ( CSF1R/ FMS), stem cell factor receptor (SCFR/

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), and platelet derived growth factor receptors ( PDGFRs). Mutations cause constant activation of the FLT3 pathway resulting in inhibition of ligand-independent leukemic cell proliferation and apoptosis.

Clinical trials

It reported good results in 2012 from a phase II clinical trial for refractory AML - particularly in patients who went on to have a stem cell transplant.Drug Tames Refractory AML. ASH Dec 2012
/ref> , it has completed five clinical trials, and another seven are active.Quizartinib studies
/ref>

References

{{Growth factor receptor modulators Experimental cancer drugs Receptor tyrosine kinase inhibitors 4-Morpholinyl compunds Isoxazoles Ureas Tert-butyl compounds Ethers