A 419259 trihydrochloride Chemical Properties

Boiling point:

686.4±55.0 °C(Predicted)

Density 

1.29±0.1 g/cm3(Predicted)

storage temp. 

room temp

solubility 

H2O: soluble10mg/mL (clear solution)

form 

powder

pka

8.20±0.42(Predicted)

color 

white to beige

Water Solubility 

H2O: 10mg/mL (clear solution)

InChIKey

ALRMEQIQFCUAMR-KOONDFAVSA-N

SMILES

Cl.Cl.Cl.CN1CCN(CC1)[C@H]2CC[C@@H](CC2)n3cc(-c4ccc(Oc5ccccc5)cc4)c6c(N)ncnc36

Safety Information

WGK Germany 

3

Storage Class

11 - Combustible Solids

A 419259 trihydrochloride Usage And Synthesis

Description

A-419259 is an inhibitor of Src family kinases, including Src, LCK, Lyn, and Hck (IC₅₀s = 9, <3, <3, and 11.26 nM, respectively)., It is selective for these kinases over c-Abl (IC₅₀ = 3,000 nM) and PKC (IC₅₀ = >33 μM). A-419259 inhibits growth of Philadelphia chromosome-positive (Ph⁺) K-562 and Meg-01 myeloid leukemia cells (IC₅₀s = 0.1-0.3 and 0.1 μM, respectively), but not Ph^- TF-1 and HEL cells. It induces apoptosis in K-562 cells in a concentration-dependent manner. A-419259 (300 nM) inhibits differentiation of murine embryonic stem cells while maintaining pluripotency. It reduces the total number of acute myeloid leukemia (AML) cells, as well as AML stem cells, in the bone marrow and spleen in mouse patient-derived xenograft (PDX) models of AML when administered at a dose of 30 mg/kg twice daily.

Uses

A 419259 Trihydrochloride is the hydrochloride form of A 419259 which is a Src kinase inhibitor and can be used in treatment of chronic myelogenous leukemia, lymphangioleiomyomatosis and tuberous sclerosis.

References

[1] MATTHEW B WILSON. Selective pyrrolo-pyrimidine inhibitors reveal a necessary role for Src family kinases in Bcr–Abl signal transduction and oncogenesis[J]. Oncogene, 2002, 21 53: 8075-8088. DOI: 10.1038/sj.onc.1206008
[2] T PENE-DUMITRESCU. An inhibitor-resistant mutant of Hck protects CML cells against the antiproliferative and apoptotic effects of the broad-spectrum Src family kinase inhibitor A-419259[J]. Oncogene, 2008, 27 56: 7055-7069. DOI: 10.1038/onc.2008.330
[3] MALCOLM A MEYN. SRC family kinase activity is required for murine embryonic stem cell growth and differentiation.[J]. Molecular Pharmacology, 2005, 68 5: 1320-1330. DOI: 10.1124/mol.104.010231
[4] YORIKO SAITO. A Pyrrolo-Pyrimidine Derivative Targets Human Primary AML Stem Cells in Vivo[J]. Science Translational Medicine, 2013, 5 181. DOI: 10.1126/scitranslmed.3004387