Bosutinib Treatment for Philadelphia Chromosome-Positive Leukemias

Bethelmie-Bryan, Beverly; Lord, Katharine; Holloway, Stacie; Khoury, H. Jean

doi:10.2217/fon.13.268

Cited by 5 publications

(13 citation statements)

References 18 publications

(12 reference statements)

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“…Bosutinib is the newest second-generation TKI, and can effectively treat patients with kinase domain mutations other than T315I and V299L 25,26. As opposed to bosutinib, the newest TKI, ponatinib, does not confer resistance with any known kinase domain mutations, and is the only one that produces a response in patients with T315I mutations 13,14.…”

Section: Treatment Options In CMLmentioning

confidence: 99%

“…Bosutinib (SKI606) is a dual BCR-ABL and SRC (steroid receptor co-activator)-ABL TKI 26,31,32. SRC family kinases have repeatedly been implicated in tumor progression in various solid tumors; however, emerging data support their role in BCR-ABL-independent forms of resistance and disease progression in CML as well 33–35…”

Section: Pharmacology Of Bosutinibmentioning

confidence: 99%

“…It is a monohydrate 4-([2,4-dichloro-5-methylphenyl]amino)-6-methoxy-7-(3-[4-methylpiperazin-1-yl]propoxy)quinolone-3-carbonitrile (Figure 1). 25,26…”

Section: Pharmacology Of Bosutinibmentioning

confidence: 99%

“…This potential side effect was not seen in those with normal liver function 37. Ninety-one percent of the drug is excreted in the feces and 3% in the urine 25,26. Bosutinib exposure is impacted by coadministration with other CYP3A4 inducers or inhibitors, such as rifampin or ketoconazole, and these drugs should not be given concomitantly 25,26.…”

Section: Pharmacology Of Bosutinibmentioning

confidence: 99%

“…Ninety-one percent of the drug is excreted in the feces and 3% in the urine 25,26. Bosutinib exposure is impacted by coadministration with other CYP3A4 inducers or inhibitors, such as rifampin or ketoconazole, and these drugs should not be given concomitantly 25,26. Absorption is pH-dependent; the solubility of bosutinib decreases as the pH in the stomach increases.…”

Section: Pharmacology Of Bosutinibmentioning

confidence: 99%

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Clinical advances in the management of chronic myelogenous leukemia: focus on bosutinib and patient considerations

Sweet¹,

Pinilla‐Ibarz²,

Zhang³

2014

PPA

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The treatment for chronic myeloid leukemia has changed significantly over the past 15 years, and as of now, there are five BCR-ABL1 (breakpoint cluster region-Abelson murine leukemia viral oncogene homolog 1) tyrosine kinase inhibitors that have gained approval for treatment of this disease. All five are very effective drugs, and the decision surrounding which to use in specific patients is based on numerous factors. Bosutinib is one of the newer tyrosine kinase inhibitors to gain approval, and has been studied in the first-line setting as well as after failure of other tyrosine kinase inhibitors. It is an SRC-ABL1 (steroid receptor co-activator-ABL1) inhibitor that works in the presence of most kinase domain mutations. The primary side effects of bosutinib are gastrointestinal upsets. In the appropriate clinical setting, bosutinib can be considered a valuable addition to the armamentarium of treatments available for chronic myeloid leukemia.

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Section: Treatment Options In CMLmentioning

confidence: 99%

Section: Pharmacology Of Bosutinibmentioning

confidence: 99%

“…It is a monohydrate 4-([2,4-dichloro-5-methylphenyl]amino)-6-methoxy-7-(3-[4-methylpiperazin-1-yl]propoxy)quinolone-3-carbonitrile (Figure 1). 25,26…”

Section: Pharmacology Of Bosutinibmentioning

confidence: 99%

Section: Pharmacology Of Bosutinibmentioning

confidence: 99%

Section: Pharmacology Of Bosutinibmentioning

confidence: 99%

See 3 more Smart Citations

Clinical advances in the management of chronic myelogenous leukemia: focus on bosutinib and patient considerations

Sweet¹,

Pinilla‐Ibarz²,

Zhang³

2014

PPA

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Safety, target engagement, and biomarker effects of bosutinib in dementia with Lewy bodies

Pagán

Torres‐Yaghi

Hebron

et al. 2022

A&D Transl Res & Clin Interv

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Introduction: Bosutinib, a dual Abelson/Src inhibitor, was investigated in individuals with dementia with Lewy bodies (DLB).Methods: A single site, randomized, double-blind, placebo-controlled study of the effects of oral bosutinib, 100 mg once daily for 12 weeks on primary safety and pharmacokinetics and secondary biomarker outcomes.Results: Twenty-six participants were randomized and included male and female (12:1) in the bosutinib arm and all male (13) in the placebo arm. The average age was 72.9 ± 8.1 (year ± standard deviation). There were no serious adverse events and no dropouts.Bosutinib was measured in the cerebrospinal fluid (CSF) and inhibited Abelson. Bosutinib reduced CSF alpha-synuclein and dopamine catabolism.Discussion: Bosutinib is safe and well tolerated and penetrates the blood-brain barrier to inhibit Abelson and reduce CSF alpha-synuclein and dopamine catabolism, suggesting that bosutinib (100 mg) may be at or near the lowest effective dose in DLB. These results will guide adequately powered studies to determine the efficacy of a dose range of bosutinib and longer treatment in DLB. K E Y W O R D SAbelson, activities of daily living, alpha-synuclein, dementia with Lewy bodies, dopamine Highlights• Bosutinib is a dual Abl/Src inhibitor that penetrates the blood brain barrier• Bosutinib is safe and tolerated in individuals with dementia with Lewy bodies• Bosutinib engages its target via inhibition of Abl and Src• Bosutinib reduces CSF alpha-synuclein and attenuates breakdown of dopamine • Bosutinib improves activities of daily living in dementia with Lewy bodiesThis is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

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Determination of bosutinib in mice plasma and tissue by UPLC-MS/MS and its application to the pharmacokinetic and tissue distribution study

et al. 2015

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A sensitive and rapid ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method was developed to determine bosutinib in mice plasma and tissue using diazepam as the internal standard (IS). Sample preparation was accomplished through a protein precipitation procedure with acetonitrile. The analyte and IS were separated on an Acquity UPLC BEH C18 column (2.1 mm Â 50 mm, 1.7 mm) with the mobile phase of acetonitrile and 0.1% formic acid in water with gradient elution at a flow rate of 0.40 mL min À1 . The detection was performed on a triple quadrupole tandem mass spectrometer equipped with electrospray ionization (ESI) by multiple reaction monitoring (MRM) of the transitions at m/z 530.3 / 141.1 for bosutinib and m/z 285.2 / 193.1 for the IS. The linearity of this method was found to be within the concentration range of 5-3000 ng mL À1 with a lower limit of quantification of 5.0 ng mL À1 . Only 3.0 min was needed for an analytical run. The method herein described was superior to previous methods and was successfully applied to the pharmacokinetic and tissue distribution study of bosutinib in mice after oral administration.

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Bosutinib Treatment for Philadelphia Chromosome-Positive Leukemias

Cited by 5 publications

References 18 publications

Clinical advances in the management of chronic myelogenous leukemia: focus on bosutinib and patient considerations

Clinical advances in the management of chronic myelogenous leukemia: focus on bosutinib and patient considerations

Safety, target engagement, and biomarker effects of bosutinib in dementia with Lewy bodies

Determination of bosutinib in mice plasma and tissue by UPLC-MS/MS and its application to the pharmacokinetic and tissue distribution study

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