bosutinib

Bosutinib is a substrate of P-glycoprotein (P-gp) in vitro and is predominantly metabolized by CYP3A4 in humans with minimal urinary excretion. We present our perspective on using physiologically based pharmacokinetic modeling to understand the atypical changes in oral exposure of bosutinib, a CYP3A and P-gp substrate, in hepatic impairment patients.

Case 1 developed unilateral then bilateral knee BME, temporally associated first with dasatinib and subsequently with imatinib; symptoms improved after TKI interruption, bisphosphonate therapy, and supportive measures, and did not recur after switching to bosutinib. Case 2 presented with proximal femoral BME during long-term imatinib; imatinib was stopped, intravenous neridronate administered, and bosutinib initiated with clinical recovery and later near-complete radiological resolution...Prompt recognition with targeted MRI and a multidisciplinary, stepwise approach that includes temporary TKI adjustment, bone-directed therapy, and consideration of PDGFR-sparing alternatives can mitigate morbidity while maintaining disease control. Prospective studies are needed to define incidence, risk factors, optimal prevention, and management strategies.

These include bosutinib, sorafenib, mitoxantrone, and nintedanib which are yet to be clinically investigated for vestibular schwannoma or meningioma. Drug repurposing may offer an expedited route to the clinical translation of approved drugs effective for treating both meningioma and vestibular schwannoma to benefit NF2-related schwannomatosis patients.

P2, N=100, Recruiting, Baylor College of Medicine | Trial completion date: Nov 2025 --> Nov 2028 | Trial primary completion date: Nov 2025 --> Nov 2028

Since then, four other tyrosine kinase inhibitors (TKIs), dasatinib, nilotinib, bosutinib and most recently asciminib, have garnered approval for frontline management of CML-CP. With limited prospective comparisons between the 2G-TKIs and similar survival outcomes with imatinib compared to 2G-TKIs, the selection of a TKI for patients with newly diagnosed CML-CP must be individualized to the needs of that specific patient. Important factors to consider when choosing a drug include patient related factors (age, comorbidities, lifestyle considerations, quality of life, patient preferences, shared-decision making and whether treatment free remission [TFR] is a goal), disease related factors (risk stratification, transcript type, presence of high risk gene mutations such as ASXL1) and drug related factors (major molecular response rates with each TKI, adverse events, rates of treatment discontinuation and TFR rates).

P=N/A, N=600, Active, not recruiting, Pfizer | Not yet recruiting --> Active, not recruiting | Trial completion date: Dec 2029 --> Jun 2028 | Trial primary completion date: Dec 2029 --> Jun 2028

P3, N=406, Active, not recruiting, Novartis Pharmaceuticals | Trial completion date: Jan 2031 --> Jan 2028

TKIs, including flumatinib, may cause AKI; however, FAERS-based disproportionality analysis does not indicate an increased renal safety signal compared to non-TKIs. Among TKIs, dasatinib and nilotinib have lower reporting disproportionality than imatinib does, suggesting a potential therapeutic advantage of their use for patients with kidney diseases.

It was found to inhibit the c-Src-mediated kinase activity (IC50: 517 nM) in comparison to the positive control, bosutinib (IC50: 408 nM). The compound was also able to increase the oxidative stress and induce apoptosis in the colorectal cancer cells employed. The study thus may pave the way for exploration of the top identified ligands further to develop and establish their potential as c-Src kinase inhibitors with anticancer potential.

We evaluated their effects on resistance to five TKIs (imatinib, nilotinib, bosutinib, ponatinib and asciminib), spanning all four TKI generations by using K562 cells. We identified 361 pairs of resistance-conferring single amino acid variants and the corresponding TKIs. Our comprehensive resistance map will complement clinical guidelines in drug selection for patients with chronic myeloid leukaemia based on ABL1 mutations, facilitating precision medicine.

This study reveals immune-molecular interactions in GBM, identifies AEBP1/EFEMP2 as prognostic markers, and proposes targeted therapies for personalized treatment.

This study introduces a microfluidic cell culture array for the comparative analysis of six BCR::ABL1 TKIs, namely imatinib, nilotinib, bosutinib, ponatinib, dasatinib, and asciminib, using CML-related cell lines. We further validated the device with a CML patient-derived bone marrow sample, requiring only minimal adjustments to the experimental conditions. The proposed microfluidic single-cell-based screening array could refine treatment regimens and advance personalized medicine in CML.