Rylaze-BI4916 treatment in AML cell lines led to the inhibition of cap-dependent mRNA translation and protein synthesis, as well as a marked decrease in intracellular glutathione levels, a critical cellular antioxidant. Collectively, our results highlight the clinical potential of targeting serine biosynthesis in combination with crisantaspase as a novel therapeutic strategy for AML.

P=N/A, N=60, Active, not recruiting, Singapore General Hospital | Recruiting --> Active, not recruiting | Trial completion date: Nov 2023 --> Dec 2024 | Trial primary completion date: Jun 2023 --> Jun 2024

P1, N=42, Recruiting, Merck Sharp & Dohme LLC | Not yet recruiting --> Recruiting

P4, N=51, Completed, Beijing Stomatological Hospital, Capital Medical University | Not yet recruiting --> Completed

P3, N=81, Recruiting, First Affiliated Hospital of Zhejiang University | Not yet recruiting --> Recruiting

Acute myeloid leukaemia (AML) is a fatal haematopoietic malignancy and is treated with the conventional combination of cytarabine (Ara-C) and daunorubicin (Dau). HHT synergistically induces apoptosis in combination with Ara-C in vitro and prolongs the survival of xenografts. We provide a new mechanism for AML treatment by regulating the p38 MAPK/H2AX/Mcl-1 axis to improve cytarabine therapy.

P2, N=200, Active, not recruiting, Prisma Health-Upstate | Recruiting --> Active, not recruiting

Finally, we demonstrated that rutin significantly improves the bacteriostatic effect of GM by in vitro experiments, emphasising its clinical application value. In summary, these results collectively unravel a novel therapeutic role for rutin as an otoprotective drug against the adverse effects of GM.

P=N/A, N=137, Completed, Medecins Sans Frontieres, Netherlands | Recruiting --> Completed | N=54 --> 137

P2/3, N=73, Completed, Medecins Sans Frontieres, Netherlands | Recruiting --> Completed | N=200 --> 73

Moreover, c-FLIP overexpression significantly increased the expression and phosphorylation of SMAD2/3 proteins and vice versa. In conclusion, our study reveals c-FLIP/SMAD2/3 signaling pathway as a novel mechanism of antitumor activity of thiostrepton.

Furthermore, its inhibitory effects on TNF-α and IL-6 levels were even better than those of minocycline. The significant anti-neuroinflammatory activity of AOPB-1-1 suggests its applicability as a therapeutic option for the treatment of Alzheimer's disease.

P2, N=58, Recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Jul 2024 --> Jul 2025 | Trial primary completion date: Jul 2024 --> Jul 2025

P2, N=26, Not yet recruiting, University Hospital, Toulouse

P3, N=81, Not yet recruiting, First Affiliated Hospital of Zhejiang University

Targeting MILIP inhibited TNBC growth and cooperated with the clinically available protein synthesis inhibitor omacetaxine mepesuccinate in vivo. Collectively, these results identify MILIP as an RNA translation elongation factor that promotes protein production in TNBC cells and reveal the therapeutic potential of targeting MILIP, alone and in combination with other types of protein synthesis inhibitors, for TNBC treatment. LncRNA MILIP plays a key role in supporting protein production in TNBC by forming complexes with tRNAs and eEF1α1, which confers sensitivity to combined MILIP targeting and protein synthesis inhibitors.

Homoharringtonine, a Food And Drug Administration-approved translation elongation inhibitor, impedes CRPC progression in preclinical models and patients with CRPC. We construct an SCLPC-specific signature capable of stratifying patients for drug selectivity. Our studies reveal the existence of SCLPC in admixed PCa pathology, which may mediate tumor relapse, and establish SP1 and translation elongation as actionable therapeutic targets for CRPC.

P4, N=300, Recruiting, University of Michigan | Trial primary completion date: Sep 2024 --> Sep 2026

These findings further confirmed the anticancer effect of minocycline and highlighted that minocycline maybe considered as potential therapeutic agent for breast cancer treatment.

Despite these promising in vitro effects, omacetaxine's efficacy in an orthotopic DIPG model was limited due to inadequate penetration across the blood-brain barrier. As such, further research and advancements are crucial to improve the drug's brain penetration, thus enhancing its overall therapeutic potential.

P1, N=20, Recruiting, National Institute of Allergy and Infectious Diseases (NIAID) | Trial completion date: Jan 2024 --> May 2024 | Trial primary completion date: Jan 2024 --> May 2024

Treatment with thiostrepton, a FOXM1 inhibitor, not only suppressed ASF1B expression, but also inhibited GC progression...The crucial role of ASF1B-regulated PRDX3 in GC cell proliferation and oxidative stress balance was also elucidated. In summary, our study suggests that the FOXM1-ASF1B-PRDX3 axis is a potential therapeutic target for treating GC.

P=N/A, N=600, Recruiting, Shanghai Jiao Tong University School of Medicine

P1, N=38, Active, not recruiting, Kaken Pharmaceutical | Recruiting --> Active, not recruiting | Trial completion date: Feb 2024 --> Jul 2024

P4, N=30, Not yet recruiting, Women and Infants Hospital of Rhode Island

P2, N=412, Not yet recruiting, Yale University | Initiation date: Jan 2024 --> May 2024

P4, N=400, Recruiting, St. Joseph's Hospital and Medical Center, Phoenix

P=N/A, N=34, Recruiting, Huai'an First People's Hospital

The synergy of AZA+HHT on apoptosis was induced by activating c-MYC/DDIT3/PUMA-mediated ISR signaling. The combination of AZA and HHT exerts synergistic anti-AML effects by inhibiting cellular proliferation and promoting apoptosis through activation of the ISR signaling pathway via the c-MYC/DDIT3/PUMA axis.

P1/2, N=29, Active, not recruiting, University of Colorado, Denver | Recruiting --> Active, not recruiting | N=45 --> 29

Except for the increased IL-6, these changes were prevented by a microglia activation inhibitor, minocycline. The findings suggest that neuroinflammation due to polarization of M1-type hippocampal microglia is involved in depression accompanied with olfactory dysfunction.

P3, N=1500, Recruiting, Novartis Pharmaceuticals | Not yet recruiting --> Recruiting

This work provides proof of concept for further investigation of extracorporeal cytokine adsorption as a potential adjunct treatment for equine sepsis.

They exhibited a higher efficiency in inhibiting gastric cell inflammation mediated by H. pylori infection than free CLA. The establishment of KPEVs-CLA as a nanodrug delivery model for H. pylori treatment could be applied to other plant extracellular vesicles or loaded with other cancer drugs for gastric cancer treatment.

P2, N=300, Recruiting, Global Alliance for TB Drug Development | Not yet recruiting --> Recruiting

Citronellol with its antioxidant and anti-inflammatory properties can decrease kidney damage caused by nephrotoxicity induced by gentamicin.

P1, N=16, Recruiting, University of Oxford | Trial completion date: Aug 2023 --> Aug 2026 | Trial primary completion date: Aug 2023 --> Aug 2026

P1, N=42, Not yet recruiting, Merck Sharp & Dohme LLC

P3, N=6174, Suspended, University of Western Australia | Recruiting --> Suspended

P2, N=30, Recruiting, First Affiliated Hospital of Zhejiang University | Trial completion date: Aug 2024 --> Jun 2025 | Initiation date: Oct 2022 --> Jun 2023 | Trial primary completion date: Dec 2023 --> Dec 2024

Inhibition of FOXM1 using thiostrepton also reduced tumor cell viability in a dose-dependent manner. These findings suggest that FOXM1 is a promising therapeutic target for patients with EMPD.

P1, N=56, Completed, KBP Biosciences | Active, not recruiting --> Completed | Trial completion date: Jan 2024 --> Jun 2023