bafetinib (INNO-406)

Five candidate compounds emerged with binding energies comparable to or higher than known Abl kinase inhibitors, including Imatinib and Bafetinib. Finally, based on these calculations, we selected two compounds as candidates as Abl tyrosine kinase inhibitors. Overall, the results showed the effectiveness of combining ligand-based and structure-based drug design strategies to identify new Abl kinase inhibitor leads for improved the CML therapy.

Newer BCR-ABL TKIs provide superior cancer outcomes but with increased risk of acute arterial thrombosis, which further increases in patients with cardiovascular comorbidities and mitigates survival benefits compared to imatinib...Of the new agents, bafetinib decreased EC viability and increased microvessel permeability while asciminib and radotinib did not impact any EC function tested. In summary, the vasculotoxic TKIs (dasatinib, ponatinib, nilotinib) cause EC toxicity but with mechanistic differences, supporting the potential need for drug-specific vasculoprotective strategies. Asciminib and radotinib do not induce EC toxicity at clinically relevant concentrations suggesting a better safety profile.

Among them, dasatinib and bosutinib, and imatinib and bafetinib showed homologous profiling. The tyrosine kinase inhibitors mentioned above are approved as anticancer agents, and the system could be used for similarity evaluation, efficacy prediction, etc., in the development of new anticancer agents.

Our findings provide novel insights into the tumor-suppressive function of ASPA in PCa and highlight its potential as a prognostic biomarker and therapeutic target for the management of this malignancy.

The potential mechanisms of the five RNAs were also explored via gene set enrichment analysis, and candidate drugs targeting the five genes, including dabrafenib, vemurafenib, and bafetinib, were screened. In conclusion, we constructed a five-RNA-based signature to predict the survival of NBL and screened candidate agents against NBL.

Material and Methods We used four SFK inhibitors: dasatinib, bosutinib, saracatinib, and bafetinib, and measured sensitivity to these drugs for 30 cancer cell lines belonging to 12 different cancer types...Doxorubicin increased expression of all SFKs in HT-29 colon cancer cells and, in combination with dasatinib, also had a synergistic effect on cell growth...These findings have the potential to improve future strategies for the use of SFKs inhibitors in cancer treatment. This study was funded by RFBR, project number 20-34-70119.

Material and Methods We used four SFK inhibitors: dasatinib, bosutinib, saracatinib, and bafetinib, and measured sensitivity to these drugs for 30 cancer cell lines belonging to 12 different cancer types...Doxorubicin increased expression of all SFKs in HT-29 colon cancer cells and, in combination with dasatinib, also had a synergistic effect on cell growth...These findings have the potential to improve future strategies for the use of SFKs inhibitors in cancer treatment. This study was funded by RFBR, project number 20-34-70119.

Material and Methods We used four SFK inhibitors: dasatinib, bosutinib, saracatinib, and bafetinib, and measured sensitivity to these drugs for 30 cancer cell lines belonging to 12 different cancer types...Doxorubicin increased expression of all SFKs in HT-29 colon cancer cells and, in combination with dasatinib, also had a synergistic effect on cell growth...These findings have the potential to improve future strategies for the use of SFKs inhibitors in cancer treatment. This study was funded by RFBR, project number 20-34-70119.

Material and Methods We used four SFK inhibitors: dasatinib, bosutinib, saracatinib, and bafetinib, and measured sensitivity to these drugs for 30 cancer cell lines belonging to 12 different cancer types...Doxorubicin increased expression of all SFKs in HT-29 colon cancer cells and, in combination with dasatinib, also had a synergistic effect on cell growth...These findings have the potential to improve future strategies for the use of SFKs inhibitors in cancer treatment. This study was funded by RFBR, project number 20-34-70119.

These findings may elucidate the roles played by HER family gene in cancer progression and providing insights for further investigation of the HER family gene as potential targets in pan-cancer.