Kinaction (masitinib)

Masitinib counteracted PGK1 upregulation by CSTF2 and suppressed the growth of HCC xenograft and patient-derived organoid models. In conclusion, this study revealed a function of CSTF2 in supporting HCC survival under hypoxia conditions through m6A modification evasion and metabolic reprogramming, indicating inhibiting CSTF2 may overcome hypoxia tolerance in HCC.

Finally, 4 KGs-guided repositioning candidate drugs (ZSTK474, GSK2126458, Masitinib, and Trametinib) were proposed. The stability of three top-ranked drug-target interactions (CAV1 vs. ZSTK474, CAV1 vs. GSK2126458, and ASPM vs. Trametinib) were investigated by computing their binding free energies for 140 ns MD-simulation based on MM-PBSA approach. Therefore, the findings of this computational study may be useful for early prognosis, diagnosis and therapies of NSCLC.

Finally, we suggested hHubGs-guided top-ranked 10 candidate drug molecules (SORAFENIB, AMG-900, CHEMBL1765740, ENTRECTINIB, MK-6592, YM201636, masitinib, GSK2126458, TG-02, and PAZOPANIB) by molecular docking analysis for the treatment against BC. The literature review also supported our findings much more for BC compared with the results of individual studies. Therefore, the findings of this study may be useful resources for early diagnosis, prognosis, and therapies of BC.

In conclusion, we constructed five cuprotosis-related lncRNA prognostic models, which may be new tumor therapeutic targets for the prevention and treatment of cervical cancer.

P3, N=600, Not yet recruiting, AB Science | Trial completion date: Dec 2025 --> Dec 2026 | Trial primary completion date: Nov 2025 --> Dec 2026

In veterinary medicine, the world's first molecular-targeted drug for animals, masitinib, was approved in 2008, followed by the multikinase inhibitor toceranib in 2009...Although there has been no progress in the development and commercialization of new molecular-targeted drugs for the treatment of cancer since the success of toceranib, several clinical trials have recently reported the administration of novel agents in the research stage to dogs with tumors. This review provides an overview of molecular-targeted drugs for canine tumors, particularly transitional cell carcinomas, and presents some of our recent data.

Cell-based assays indicated that masitinib and simvastatin had specific effects on CHS1 and CHS3, respectively. A user-friendly website based on the classifier was developed (https://fan-app.shinyapps.io/chs_classifier/) for accessibility. Overall, the classifier based on cuproptosis and hypoxia was applicable to most pan-cancers and could aid in personalized cancer therapy.

The active agents in our analysis as post-first-line therapies are able to provide superior clinical efficacy, with improved PFS rate and OS rate at certain time points, as well as absolute values of PFS and OS for advanced GIST. Ripretinib might be the optimal recommendation as a post-first-line treatment for advanced GIST following imatinib failure.

Our lead compound, OR0642, is more than 1000 times more potent than its initial parent compound, masitinib, previously identified from a drug repositioning approach. OR0642 in combination with a physiological inhibitor of the de novo pathway doubled the survival rate in a human T-cell acute lymphoblastic leukemia patient-derived xenograft mouse model, demonstrating the proof-of-concept of this drug design strategy.

The expression of ASPHD1 in SKCM patients is closely related to patient survival. ASPHD1 may participate in the regulation of tumor immune microenvironment. Additionally, it may serve as a prognostic biomarker for SKCM and future in-depth studies are necessary to explore its value.

Finally, we proposed 16 candidate repurposing drugs YM201636, masitinib, SB590885, GSK1070916, GSK2126458, ZSTK474, dasatinib, fedratinib, dabrafenib, methotrexate, trametinib, tubastatin A, BIX02189, CP466722, afatinib, and belinostat for BC through molecular docking analysis. Using BC cell lines, we validated that masitinib inhibits the mTOR signaling pathway and induces apoptotic cell death. Therefore, the proposed results might play an effective role in the treatment of BC patients.

Thus, we demonstrated that the anticancer effects of masitinib are not due to its targeting c-kit, but rather to its targeting the redox balance via the JNK pathway in HepG2 cells. These results suggest that masitinib has the potential to provide a robust antitumor effect in tumor lesions and could also be applied to a broad range of other anticancer therapies.

High expression of HIST1H1E was resistant to trametinib, selumetinib, RDEA119, docetaxel and 17-AAG, High expression of UBE2C was resistant to masitinib, and Low expression of ERO1B made the EC more sensitive to FK866. We constructed an EC risk score model composed of 8 DEGs and gene resistance analysis, which can provide reference for prognosis prediction, diagnosis and treatment of the EC patients.

Given the polymorphic nature of the enzymes involved, future studies are needed to determine the impact of CYP genetic polymorphisms on masitinib metabolism. This information could ultimately provide evidence to inform precision prescribing for masitinib to ensure safety and efficacy for future patients.

VL51 developed resistance to idelalisib, copanlisib, duvelisib, and umbralisib...The use of the IL-6R blocking antibody tocilizumab, the STAT3 inhibitor stattic, the LIN28 inhibitor LIN1632, the PDGFR inhibitor masitinib and the anti-CD19 antibody drug conjugate loncastuximab tesirine were active compounds in the resistant cells as single agents and/or in combination with PI3K//inhibition. Findings were validated on additional in vitro lymphoma models and on clinical specimens. A novel model of resistance obtained from splenic MZL allowed the identification of therapeutic approaches able to improve the anti-tumor activity of PI3Kttinhibitors in B-cell lymphoid tumors.

Masitinib exposure increased apoptosis, while the cell counts and cell viability decreased in a dose- and application interval-dependent manner, with increased impact in the 12-h double-dose regimen. These in vitro effects of masitinib in canine prostate cancer and associated metastasis support further in vivo research and modifications of the clinical treatment protocol in future studies.

Finally, potential therapeutic drugs, such as masitinib, were obtained by the cMap database. miR-1 may play a vital part in NPC tumorigenesis and progression by regulating focal adhesion kinase to participate in cell mitosis, regulating ECM degradation, and affecting the PI3K/Akt signaling pathway. miR-1 has the potential to be a therapeutic target for NPC.

We propose combination therapy of masitinib and cromolyn may represent an innovative treatment in neurodegenerative diseases. Combination therapy may be more advantageous that it enables combined application of lower doses of both drugs, providing less side effects.

Our results suggest that tissue parameters increased from ANT to PDAT and that mast cells are strongly associated with angiogenesis in PDAT. On this basis, the inhibition of MCs through tyrosine kinase inhibitors, such as masitinib, or inhibition of tryptase by gabexate mesylate may become potential novel antiangiogenetic approaches in pancreatic cancer therapy.

P3, N=258, Completed, AB Science | Active, not recruiting --> Completed | Trial completion date: Jun 2020 --> Dec 2020 | Trial primary completion date: Jun 2020 --> Dec 2020

Patients with GIST who received investigational MKIs as first-line treatment and imatinib as second line had a time to second relapse longer than that observed historically with imatinib in first line, suggesting that using MKIs other than imatinib in first line does not decrease the efficacy of subsequent treatment lines.

Mutant cell lines had significantly higher IC50 compared to WT for the drugs Ibrutinib, Idelalisib and Masitinib, but not Bortezomib, suggesting that NKFBIZ UTR mutations confer resistance to drugs specifically targeting the NF-κB pathway. This work directly establishes a role for NFKBIZ amplifications and 3′ UTR mutations in driving ABC DLBCL through NF-κB signaling. We demonstrate that these mutations can cause over-expression of NFKBIZ and provide a selective growth advantage to tumor cells. We also identified novel targets of NFKBIZ including HCK and PD-L1, both of which have implications as therapeutic targets in this subset of DLBCLs.

Studies with Kit inhibitor Imatinib showed response rates ranging from 20 to 30%. We present the case of a patient with a c-kit mutated metastatic melanoma who developed autoimmune vitiligo during treatment with oral tyrosine kinase inhibitor Masitinib.