| Identification | Back Directory | [Name]
3-(6,7-dimethoxyquinazolin-4-yloxy)-N-(4-((4-ethylpiperazin-1-yl)methyl)-3-(trifluoromethyl)phenyl)-4-methylbenzamide | [CAS]
1315330-17-6 | [Synonyms]
TL02-59
TL-02-59,Inhibitor,Lyn,Apoptosis,leukemia,inhibit,acute,Src,orally,AML,TL02-59,TL02 59,TL0259,Hck,myelogenous,Fgr
3-(6,7-dimethoxyquinazolin-4-yloxy)-N-(4-((4-ethylpiperazin-1-yl)methyl)-3-(trifluoromethyl)phenyl)-4-methylbenzamide
Benzamide, 3-[(6,7-dimethoxy-4-quinazolinyl)oxy]-N-[4-[(4-ethyl-1-piperazinyl)methyl]-3-(trifluoromethyl)phenyl]-4-methyl- | [Molecular Formula]
C32H34F3N5O4 | [MDL Number]
MFCD29991221 | [MOL File]
1315330-17-6.mol | [Molecular Weight]
609.64 |
| Chemical Properties | Back Directory | [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) | [form ]
Solid | [pka]
12.86±0.70(Predicted) | [color ]
White to off-white | [InChIKey]
AMHWQBGAKJESFB-UHFFFAOYSA-N | [SMILES]
O=C(NC1=CC(C(F)(F)F)=C(CN2CCN(CC)CC2)C=C1)C3=CC(OC4=C(C=C(C(OC)=C5)OC)C5=NC=N4)=C(C)C=C3 |
| Hazard Information | Back Directory | [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 kinasea Src-family kinase expressed in myeloid cells and associated with acute myelogenous leukemia (AML). It exhibited an IC50 value of 0.03 nM for Fgr0.10 nM for related Src-family kinase Lynwith >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]
TL02-59 (oral administration; 1 and 10 mg/kg; for three weeks) completely eliminates AML cells from the spleen and peripheral blood in a mouse model of AML, while dramatically suppressing bone marrow involvement[1].
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TL02-59 has a t1/2 of 5.7 h by i.v injection and 6.5 h by p.o. administration, respectively[1]. | Animal Model: | NOD.Cg-PrkdcscidIl2rgtm1Wjl/SzJ (NSG) mice with human MV4-11 AML cells[1] | | Dosage: | 1 and 10 mg/kg | | Administration: | Oral; for three weeks | | Result: | Eliminated AML cells from the spleen and peripheral blood in a mouse model of AML, while dramatically suppressing bone marrow involvement. |
| [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 |
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