quisinostat (JNJ 26481585)

Quisinostat also showed potent activity in leiomyosarcoma (LMS) cell lines (5.82-31.32 nM), which represent an additional complex karyotype soft tissue sarcoma. Quisinostat demonstrated strong preclinical activity and synergy with standard-of-care doxorubicin in models of UPS and LMS.

We discussed some interesting examples, like HSP90 inhibitors (ganetespib), HDAC inhibitors (quisinostat), topoisomerase inhibitors (doxorubicin), and BCL-2 family antagonists (Obatoclax, TW-37), whose therapeutic activities are tightly regulated by circadian control over their molecular targets, pharmacokinetic processes, and downstream physiological pathways. Furthermore, the circadian influence extends to the tumor microenvironment and antitumor immunity, suggesting novel chrono-immunotherapy approaches. By putting together the molecular bases of these temporal dynamics, this review underscores the significant potential of chronotherapythe timed administration of drugs to improve cancer treatment by enhancing therapeutic indices and paving the way for personalized, temporally optimized oncology strategies.

In addition, a non-phosphorylatable mutant of eIF2α, a critical substrate that transduces the PERK-mediated ER stress response, abolishes apoptosis induced by HDACi, but not by the DNA damage reagent doxorubicin. HDACi reduce the sizes of tumours formed from wildtype but not eIF2αS51A-mutant cells in a xenograft model, further demonstrating the involvement of the PERK subbranch in HDACi-induced ER stress and cell death. Our study reveals novel effects of the well-studied family of HDAC inhibitors, which can be explored further in clinics to treat certain types of cancer manifested with abnormal ER stress conditions.

P2, N=63, Recruiting, University of Miami | Not yet recruiting --> Recruiting

P2, N=63, Not yet recruiting, University of Miami

Importantly, H1-0 protein levels correspond to susceptibility of BCP-ALL cells towards histone deacetylase inhibitors (HDACis) and combinatorial treatment using the H1-0-inducing HDACi Quisinostat showed promising synergism with established chemotherapeutic drugs. Taken together, our data identify H1-0 as a key regulator of the ETV6::RUNX1+ transcriptome and indicate that the addition of Quisinostat may be beneficial to target non-responsive or relapsing ETV6::RUNX1+ BCP-ALL.

A253 cells were treated with human recombinant TNFα with or without HDAC inhibitor trichostatin A (TSA) and quisinostat (JNJ-26481585). The tricellular signaling pathway JNK inhibitor SP600125 and Hippo pathway MST1/2 inhibitor XMU-MP-1 prevented the apoptosis induced by treatment using TNFα or LSR-N-ab with HDAC inhibitors. Our findings indicated that treatment with TNFα or LSR-N-ab with HDAC inhibitors might be useful in the therapy for human SDC by enhancing apoptosis.

Furthermore, these compounds caused hyperacetylation of histone H3 and α-tubulin, indicating robust cellular target engagement. Overall, in this work we have identified the HDAC inhibitor 18b with selective antiplasmodial and 9b, 9d, and 13f with selective anticancer activities, providing valuable hits for further drug development efforts aimed at creating derivatives with reduced cytotoxicity against non-cancer cells compared to quisinostat.

TRIM21 may represent a therapeutic target for tumors, and inhibiting TRIM21 could be a potential strategy for tumor treatment.

With the emphasis on urologic malignancies (testicular germ cell tumors, urothelial-, prostate-, and renal cell carcinoma), this study concluded that elevated DHRS2 levels could be indicative of a successful HDACi treatment and, thereby offering a novel putative predictive biomarker.

Several specific interventions (i.e., Quisinostat, Carnosic acid, hyperbaric oxygen, melatonin, aqueous-soluble sporoderm-removed G. lucidum spore powder, and disulfiram/copper complex) were found to dramatically induce ferroptosis cell death of OSCC via multiple mechanisms. This review highlighted the pivotal role of ferroptosis in the pathogenesis and prognosis of OSCC. Future anticancer therapeutic strategies targeting ferroptosis and its associated molecules might provide a new insight for OSCC treatment.

In current studies, targeting ΔNp63 with inducible CRISPR knockout and Histone deacetylase inhibitor Quisinostat showed that ΔNp63 is important for tumor progression and metastasis in established tumors by promoting myeloid-derived suppressor cell (MDSC) survival through tumor necrosis factor alpha...We further demonstrated that targeting ΔNp63 sensitizes chemotherapy. Overall, we showed that ΔNp63 reprograms the MDSC-mediated immunosuppressive functions in TNBC, highlighting the benefit of targeting ΔNp63 in chemotherapy-resistant TNBC.