tirbanibulin oral (KX-01 oral)

P1, N=30, Not yet recruiting, The First Hospital of Jilin University

Adding KX2-391 (Src inhibitor) rather than BML-277 (Chk-2 inhibitor) with cetuximab resulted in more cell death and apoptosis. Conversely, activation of Src with MLR-1023 mitigated the inhibitory effect of berberine alone or in combination with cetuximab. Additionally, the activities of downstream kinases of Src such as mTOR, STAT3 and the production of ROS were inhibited greatly by berberine plus cetuximab. Taken together, we concluded that the synergistic effects of BBR and cetuximab may be mediated by decreasing the activities of Src/mTOR/STAT3 and the production of ROS, thus inducing greater extent of apoptosis in cancer cells.

P1, N=30, Not yet recruiting, TCRx Therapeutics Co.Ltd

We hypothesize that tirbanibulin interacts either with the regulatory regions of EP300 through allosteric inhibition or indirectly by altering upstream signaling pathways. Given the vital role of drug repurposing, experimental investigations on tirbanibulin unanticipated effects against EP300 are an interesting future direction.

Tirbanibulin 1% ointment is a synthetic antiproliferative agent approved in 2021 by the European Union for treating actinic keratoses (AK). These results demonstrate that tirbanibulin may impact expression of HPV oncoproteins via the Src- MEK- pathway. Tirbanibulin significantly downregulates oncogenic proteins related to cell cycle regulation and cell proliferation while upregulating apoptosis pathways.

In a murine wound infection with vancomycin-resistant Enterococcus faecalis, a single intraperitoneal bosutinib injection or multiple topical applications on the wound reduce the bacterial load by approximately 10-fold, which is abolished by macrophage depletion...Other Src kinase inhibitors such as DMAT and tirbanibulin also upregulate expression of bacterial uptake markers in macrophages and enhance intracellular bacterial killing. Finally, cotreatment with bosutinib and mitoxantrone, another chemotherapeutic in clinical use, results in an additive effect on bacterial clearance in vitro and in vivo. These results show that bosutinib stimulates macrophage clearance of bacterial infections through multiple mechanisms and could be used to boost the host innate immunity to combat drug-resistant bacterial infections.

While it showed confirmed inhibitory activity against cancer cells, this substitution shifted the profile of affected targets away from Src/tubulin which were seen with the parent KX-01...Both compounds exhibited profound downregulation effects on Erk1/2 but differed on others such as GSK3α/β and C-Jun. Collectively, this study further support to the hypothesis that small structural changes might bring higher changes in their kinome profile.

OBJECTIVES: To investigate if LC-OCT may be useful in monitoring AKs changes during treatment with tirbanibulin 1% ointment. Although some limitations of our pilot study include the small sample size and the lack of biopsy before and after treatment, it confirms the efficacy and safety of tirbanibulin in treating AKs and the usefulness of LC-OCT for the therapeutic monitoring of skin tumors along with the identification of signs of apoptosis and inflammation resulting from such treatments

There are reports of successful use of topical imiquimod, photodynamic therapy (PDT) and topical 5-fluorouracil with recurrence when treatment is discontinued...He previously applied topical imiquimod, discontinued due to systemic reaction, ingenol mebutate, 5-fluorouracil, and performed PDT with low benefits...For these reasons, we used tirbanibulin ointment on the area of previous surgery and on the peripheral area (right hemi- frontal), applying it once a day for 2 cycles of 5 days with 14 days of break between the 2 cycles...Tirbanibulin has a selective action against cells that most express microtubules and its action is, ideally, to be considered more effective the greater the number of mitoses. Based on this reasoning, we used tirbanibulin in the treatment of iSCC, not as an alternative to the surgical proposal, which always remains the first-line of therapy, but as an adjuvant approach in a selected patient to reduce the risk of progression, waiting for a possible wide local excision.

Although the etiology remains unknown, its development has been associated with several factors, the most important of which is represented by trauma, sunburns, medical procedures, and topical medications, including those used to treat actinic keratoses such as imiquimod and fluorouracil. Results Tirbanibulin showed low impact on EPDS, causing only a mild worsening of the symptoms easily controlled with a short course of topical steroids while maintaining high efficacy with regard to actinic keratoses and the field of cancerization. Discussion From our experience, topical tirbanibulin is a treatment to be considered in this type of patients, as tirbanibulin induces apoptosis and not necrosis resulting in less release of proinflammatory cytokines and reduced inflammatory stimulation in comparison with other treatments in use for actinic keratoses.

These results suggested that PDGF-Rβ and SRC can be used as drug targets for suppressing NPC metastasis. Indeed, our in vivo assay using the SRC inhibitor KX2-391, clearly showed that inhibition of SRC signaling can prevent the metastasis of NPC, indicating that targeting SRC can be a promising approach to control the NPC progression.