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 kinase ...

inhibitor, originally from

Ambit Biosciences Ambit was an American pharmaceutical company focused on development of kinase inhibitor therapeutics to treat a variety of human diseases.The SEC 10K submission for 2013 indicates that the company is a "biopharmaceutical" company, which implies tha ...

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 R ...

, 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 internal tandem duplication 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 Colony stimulating factor 1 receptor (CSF1R), also known as macrophage colony-stimulating factor receptor (M-CSFR), and CD115 (Cluster of Differentiation 115), is a cell-surface protein encoded by the human ''CSF1R'' gene (known also as c-FMS). CS ...

/ FMS), stem cell factor receptor (SCFR/ KIT), and platelet derived growth factor receptors (

PDGFR Platelet-derived growth factor receptors (PDGF-R) are cell surface tyrosine kinase receptors for members of the platelet-derived growth factor (PDGF) family. PDGF subunits -A and -B are important factors regulating cell proliferation, cellu ...

s). 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