bosutinib

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.

Overall, most patients remained on treatment and achieved or maintained MMR, suggesting that asciminib was well-tolerated and effective. Results were consistent among subgroups, indicating that asciminib is an effective option for patients regardless of prior TKI used, and including those intolerant or resistant to their first TKI.

Retrospective cohort study of patients receiving imatinib, dasatinib, nilotinib, bosutinib, ponatinib, and asciminib at Memorial Sloan Kettering Cancer Center between 2001 and 2023 with dermatologic biopsy for TKI-related dAEs. Limited sample size, particularly for third-generation TKIs, limits generalizability. Understanding these differences may improve management strategies, optimizing patient quality of life and treatment continuation.

Similar to imatinib, nilotinib has limited placental transfer with no congenital malformations reported to date in women who received it later in pregnancy. Dasatinib, however, is contraindicated due to its high association with congenital abnormalities and hydrops fetalis. Ponatinib exposure has been linked to a higher incidence of Hirschsprung's disease and should be avoided in pregnancy. Although no congenital malformations have been reported with bosutinib or asciminib, data remains limited, and their use is not recommended...Hydroxyurea, while not teratogenic, may increase the risk of miscarriage and low birth weight...Shared decision-making and thorough counseling on the risks and benefits of different treatment options are essential. This review examines the potential fetotoxicity of CML therapies, focusing on TKIs and alternative treatments for pregnant women.

Treatment of these cells with SRC inhibitors (such as dasatinib, bosutinib and saracatinib) and autophagy-inducing drugs (such as Tat-BECN1, SW076956 and SW063058) demonstrated a synergistic interaction between these compounds both in vitro and in ovo using a chick Chorioallantoic Membrane (CAM) assay. Our findings elucidate a novel BAP1-SRC-BECN1-autophagy regulatory axis that can be exploited therapeutically in precision oncology through the combination of SRC inhibitors and autophagy inducers, contingent upon patient stratification for BAP1 loss.Significance: Deadly cancers with BAP1 mutations suppress autophagy by phosphorylating the autophagy regulator BECN1 via the proto-oncogene SRC. Treatment with SRC inhibitors and autophagy inducers exhibited synergism in vitro, in ovo and in patient-derived tumor organoids with BAP1 loss, paving the way for treating BAP1-deficient cancers with autophagy inducers and kinase inhibitors.

P3, N=405, Active, not recruiting, Novartis Pharmaceuticals | Trial completion date: Jan 2028 --> Jan 2031