3-(6,7-dimethoxyquinazolin-4-yloxy)-N-(4-((4-ethylpiperazin-1-yl)methyl)-3-(trifluoromethyl)phenyl)-4-methylbenzamide Chemical Properties

Boiling point:

630.5±55.0 °C(Predicted)

Density 

1.290±0.06 g/cm3(Predicted)

storage temp. 

Store at -20°C

solubility 

DMSO: 125 mg/mL (205.04 mM)

pka

12.86±0.70(Predicted)

form 

Solid

color 

White to off-white

3-(6,7-dimethoxyquinazolin-4-yloxy)-N-(4-((4-ethylpiperazin-1-yl)methyl)-3-(trifluoromethyl)phenyl)-4-methylbenzamide Usage And Synthesis

Uses

TL02-59 is an orally active, selective Src-family kinase Fgr inhibitor with an IC50 of 0.03 nM. TL02-59 inhibits Lyn and Hck with IC50s of 0.1 nM and 160 nM, respectively. TL02-59 potently suppresses acute myelogenous leukemia (AML) cell growth[1].

Biological Activity

TL02-59 is a potent inhibitor of Fgr kinase, a Src-family kinase expressed in myeloid cells and associated with acute myelogenous leukemia (AML). It exhibited an IC50 value of 0.03 nM for Fgr, 0.10 nM for related Src-family kinase Lyn, with >1000-fold less potency for all other kinases tested. TL02-59 given orally in a mouse xenograft model of AML was able to eliminate spleen and peripheral blood leukemic cells and significantly reduce bone marrow engraftment.

in vivo

References

[1] Weir MC, et al. Selective Inhibition of the Myeloid Src-Family Kinase Fgr Potently Suppresses AML Cell Growth in Vitro and in Vivo. ACS Chem Biol. 2018 Jun 15;13(6):1551-1559. DOI:10.1021/acschembio.8b00154