bosutinib hydrate

Names

[ Name ]:
bosutinib hydrate

[Synonym ]:
SKI-606 monohydrate
Bosulif (TN)
4-(2,4-dichloro-5-methoxyanilino)-6-methoxy-7-[3-(4-methylpiperazin-1-yl)propoxy]quinoline-3-carbonitrile,hydrate
UNII-844ZJE6I55
bosutinib.H2O
Bosutinib monohydrate
3-Quinolinecarbonitrile, 4-[(2,4-dichloro-5-methoxyphenyl)amino]-6-methoxy-7-[3-(4-methyl-1-piperazinyl)propoxy]-, hydrate (1:1)
4-((2,4-dichloro-5-methoxyphenyl)-amino)-6-methoxy-7-(3-(4-methyl-1-piperazinyl)-propoxy)-3-quinoline-carbonitrile monohydrate
BOSULIF
4-[(2,4-Dichloro-5-methoxyphenyl)amino]-6-methoxy-7-[3-(4-methyl-1-piperazinyl)propoxy]-3-quinolinecarbonitrile hydrate (1:1)
Bosutinib hydrate (JAN)

Biological Activity

[Description]:

Bosutinib is an oral Src/Abl tyrosine kinase inhibito with IC50 of 1.2 nM and 1 nM, respectively[1].

[Related Catalog]:

Signaling Pathways >> Protein Tyrosine Kinase/RTK >> Src

Signaling Pathways >> Protein Tyrosine Kinase/RTK >> Bcr-Abl

[Target]

IC50: 314 nmol/L (Csk, Src family protein tyrosine kinases); IC50: 2.4 nmol/L(Abl kinase).

[In Vitro]

Bosutinib (hydrate) is an active inhibitor of Bcr-Abl in several chronic myelogenous leukemia cell lines, with IC50 values in the low nanomolar range[2]. Cell Proliferation Assay[2] Cell Line: The leukemic Bcr-Abl+ cell lines (KCL22, K562, KU812, and Lama84) Concentration: 0.1 μmol/L Incubation Time: 72 h Result: Inhibited several human CML derived cell lines with IC50 values ranging from 1 to 20 nmol/L.

[In Vivo]

Bosutinib (oral gavage; 75 mg/kg twice daily or 150 mg/kg once daily) has activity against human KU812 xenografts in nude mice. Bosutinib (150 mg/kg; once daily, 5 days weekly) has activity against syngeneic Bcr-Abl WT and mutantBa/F3 xenografts[2]. Animal Model: KU812CM L xenograft model[2] Dosage: 75 mg/kg twice daily or 150 mg/kg once daily Administration: Bosutinib (oral gavage; 75 mg/kg twice daily or 150 mg/kg once daily) Result: Had the therapeutic activity and produced a dose- and schedule-dependent weight loss. Animal Model: Syngeneic Bcr-Abl WT and mutant Ba/F3 xenografts[2] Dosage: 150 mg/kg Administration: Bosutinib (150 mg/kg; once daily, 5 days weekly) Result: Decreased the rate of tumor growth and prolonged event-free survival of mice.

[References]

[1]. Jorge E Cortes, et al. Bosutinib versus imatinib in newly diagnosed chronic-phase chronic myeloid leukemia: results from the BELA trial. J Clin Oncol. 2012 Oct 1;30(28):3486-92.

[2]. Miriam Puttini, et al. In vitro and in vivo activity of SKI-606, a novel Src-Abl inhibitor, against imatinib-resistant Bcr-Abl+ neoplastic cells. Cancer Res. 2006 Dec 1;66(23):11314-22.

Chemical & Physical Properties

[ Molecular Formula ]:
C₂₆H₃₁Cl₂N₅O₄

[ Molecular Weight ]:
548.461

[ Exact Mass ]:
547.175293

[ PSA ]:
95.34000

[ LogP ]:
4.42378

Synthetic Route

Click to get detail synthetic route

Related Compounds

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