These findings underscore the promise of GSK2606414 and cisplatin co-treatment as a potent strategy to counteract ovarian cancer resistance. This combination could potentially advance therapeutic outcomes and provide a new pharmacological approach to resistant cancers.

P1, N=5, Terminated, Nerviano Medical Sciences | N=65 --> 5 | Trial completion date: Apr 2025 --> Jan 2024 | Recruiting --> Terminated; The decision is not based on emerging safety or efficacy concerns but on strategic reasons related to the changing and competitive treatment options in Multiple Myeloma

After inhibiting CSE activity with DL-propargylglycine (PPG i.p.), the renal tissue pathology in LPS-induced AKI mice was further exacerbated, leading to enhanced activation of the PERK/Bax-Bcl2 pathway. Our findings suggest that endogenous H2S influences the pathogenesis of SAKI, while exogenous H2S protects against LPS-induced AKI by inhibiting the PERK/Bax-Bcl2 pathway involved in ERS.

P1, N=124, Recruiting, Nerviano Medical Sciences | Not yet recruiting --> Recruiting

P1, N=124, Not yet recruiting, Nerviano Medical Sciences

We demonstrate that PERK mediated UPR regulates senescence reversal and its inhibition can be exploited as potential seno-therapeutic option in glioblastoma.

The chemicals identified as degradation enhancers include inhibitors of cellular signaling pathways such as poly-ADP ribosylation (PARG inhibitor PDD00017273), unfolded protein response (PERK inhibitor GSK2606414), and protein stabilization (HSP90 inhibitor luminespib). Consequently, these signal inhibitors sensitize cells to the PROTAC-induced apoptosis. These results suggest that various cell-intrinsic signaling pathways spontaneously counteract chemically induced target degradation at multiple steps, which could be liberated by specific inhibitors.

Importantly, treatment with the inhibitor did not affect substantially normal HPF cells at any used concentration. The results indicate that PERK inhibitors could potentially be applied as a targeted therapy for NSCLC.

P1, N=23, Completed, HiberCell, Inc. | Recruiting --> Completed | Phase classification: P1a --> P1 | N=36 --> 23

P1, N=65, Recruiting, Nerviano Medical Sciences | Trial primary completion date: Nov 2023 --> Jun 2024

By disrupting an adaptive stress response evoked by VEGFR-TKIs, HC-5404 presents a clinical opportunity to improve the antitumor effects of well-established standard of care therapies in RCC.

We found that the compound GSK2606414 enhanced the sensitivity of the ABCG2 substrate to the chemotherapeutic drugs mitoxantrone and doxorubicin in ABCG2-overexpressing multidrug-resistant colorectal cancer cells by increasing their intracellular accumulation without affecting the protein expression of ABCG2. Molecular docking experiments predicted that GSK2606414 could stably bind in the drug-binding pocket of ABCG2. In conclusion, GSK2606414 can sensitize ABCG2-overexpressed multidrug-resistant colorectal cancer cells to chemotherapy drugs and can be used as a potential inhibitor of ABCG2.