Quizartinib

Quizartinib
Names
	Preferred IUPAC name N-(5-tert-Butyl-1,2-oxazol-3-yl)-N′-(4-{7-[2-(morpholin-4-yl)ethoxy]imidazo[2,1-b][1,3]benzothiazol-2-yl}phenyl)urea
	Other names AC220, Vanflyta
Identifiers
CAS Number	950769-58-1 [PubChem];
3D model (JSmol)	Interactive image;
ChEBI	CHEBI:90217 ;
ChEMBL	ChEMBL576982 ;
ChemSpider	24640357 ;
IUPHAR/BPS	5658;
KEGG	D09955;
PubChem CID	24889392;
UNII	7LA4O6Q0D3 ;
CompTox Dashboard (EPA)	DTXSID70241746 ;
	show InChI
	show SMILES
Properties
Chemical formula	C29H32N6O4S
Molar mass	560.67 g·mol−1
Pharmacology
ATC code	L01EX11 (WHO)
	Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
	(what is ?)
	Infobox references

Quizartinib (AC220) is a small molecule receptor tyrosine kinase inhibitor, originally from Ambit Biosciences and later acquired by Daiichi Sankyo, that is currently under development for the treatment of acute myeloid leukaemia. Quizartinib is sold under the brand name Vanflyta in Japan.^[1] Its molecular target is FLT3, also known as CD135 which is a proto-oncogene.^[2]

Flt3 mutations are among the most common mutations in acute myeloid leukaemia due to of Flt3. The presence of this mutation is a marker of adverse outcome.

Mechanism[]

Specifically, quizartinib selectively inhibits class III receptor tyrosine kinases, including FMS-related tyrosine kinase 3 (FLT3/STK1), colony-stimulating factor 1 receptor (CSF1R/), stem cell factor receptor (SCFR/KIT), and platelet derived growth factor receptors (PDGFRs).^{[citation needed]}

Mutations cause constant activation of the FLT3 pathway resulting in inhibition of ligand-independent leukemic cell proliferation and apoptosis.^{[citation needed]}

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.^[3]

As of 2017, it has completed five clinical trials, and another seven are active.^[4]

References[]

^ "Daiichi Sankyo Launches FLT3 Inhibitor VANFLYTA® in Japan for the Treatment of Patients with Relapsed/Refractory FLT3-ITD AML". Retrieved 16 February 2021.
^ Chao, Qi; Sprankle, Kelly G.; Grotzfeld, Robert M.; Lai, Andiliy G.; Carter, Todd A.; Velasco, Anne Marie; Gunawardane, Ruwanthi N.; Cramer, Merryl D.; Gardner, Michael F.; James, Joyce; Zarrinkar, Patrick P.; Patel, Hitesh K.; Bhagwat, Shripad S. (2009). "Identification of N-(5-tert-Butyl-isoxazol-3-yl)-N'-{4-[7-(2-morpholin-4-yl-ethoxy)imidazo[2,1-b][1,3]benzothiazol-2-yl]phenyl}urea Dihydrochloride (AC220), a Uniquely Potent, Selective, and Efficacious FMS-Like Tyrosine Kinase-3 (FLT3) Inhibitor". Journal of Medicinal Chemistry. 52 (23): 7808–7816. doi:10.1021/jm9007533. PMID 19754199.
^ Drug Tames Refractory AML. ASH Dec 2012
^ Quizartinib studies

[1] "Daiichi Sankyo Launches FLT3 Inhibitor VANFLYTA® in Japan for the Treatment of Patients with Relapsed/Refractory FLT3-ITD AML". Retrieved 16 February 2021.

[2] Chao, Qi; Sprankle, Kelly G.; Grotzfeld, Robert M.; Lai, Andiliy G.; Carter, Todd A.; Velasco, Anne Marie; Gunawardane, Ruwanthi N.; Cramer, Merryl D.; Gardner, Michael F.; James, Joyce; Zarrinkar, Patrick P.; Patel, Hitesh K.; Bhagwat, Shripad S. (2009). "Identification of N-(5-tert-Butyl-isoxazol-3-yl)-N'-{4-[7-(2-morpholin-4-yl-ethoxy)imidazo[2,1-b][1,3]benzothiazol-2-yl]phenyl}urea Dihydrochloride (AC220), a Uniquely Potent, Selective, and Efficacious FMS-Like Tyrosine Kinase-3 (FLT3) Inhibitor". Journal of Medicinal Chemistry. 52 (23): 7808–7816. doi:10.1021/jm9007533. PMID 19754199.

[ASH2012-3] Drug Tames Refractory AML. ASH Dec 2012

[4] Quizartinib studies

[1]

[2]

[3]

[4]

Names

Preferred IUPAC name N-(5-tert-Butyl-1,2-oxazol-3-yl)-N′-(4-{7-[2-(morpholin-4-yl)ethoxy]imidazo[2,1-b][1,3]benzothiazol-2-yl}phenyl)urea
Other names AC220, Vanflyta
Identifiers
CAS Number	950769-58-1^Y[PubChem]
3D model (JSmol)	Interactive image
ChEBI	CHEBI:90217^Y
ChEMBL	ChEMBL576982^Y
ChemSpider	24640357^Y
IUPHAR/BPS	5658
KEGG	D09955
PubChem CID	24889392
UNII	7LA4O6Q0D3^Y
CompTox Dashboard (EPA)	DTXSID70241746
show InChI InChI=1S/C29H32N6O4S/c1-29(2,3)25-17-26(33-39-25)32-27(36)30-20-6-4-19(5-7-20)22-18-35-23-9-8-21(16-24(23)40-28(35)31-22)38-15-12-34-10-13-37-14-11-34/h4-9,16-18H,10-15H2,1-3H3,(H2,30,32,33,36)^N Key: CVWXJKQAOSCOAB-UHFFFAOYSA-N^N InChI=1/C29H32N6O4S/c1-29(2,3)25-17-26(33-39-25)32-27(36)30-20-6-4-19(5-7-20)22-18-35-23-9-8-21(16-24(23)40-28(35)31-22)38-15-12-34-10-13-37-14-11-34/h4-9,16-18H,10-15H2,1-3H3,(H2,30,32,33,36) Key: CVWXJKQAOSCOAB-UHFFFAOYAF
show SMILES CC(C)(C)c1cc(no1)NC(=O)Nc2ccc(cc2)c3cn4c5ccc(cc5sc4n3)OCCN6CCOCC6
Properties
Chemical formula	C₂₉H₃₂N₆O₄S
Molar mass	560.67 g·mol⁻¹
Pharmacology
ATC code	L01EX11 (WHO)
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
N (what is ^YN ?)
Infobox references