Aplidin (plitidepsin)

Additionally, the limited efficacy of current smallpox antivirals, such as Tecovirimat and Brincidofovir, alongside growing concerns about the emergency of tecovirimat resistance mutants, underscores the need for new therapeutic options. These findings indicate plitidepsin as a promising candidate for mpox treatment. Further studies are needed to explore its potential as a standalone or combination therapy, supporting clinical evaluation for mpox treatment.

Plitidepsin is an antitumoral compound safe for treating COVID-19 that targets the translation elongation factor eEF1A...Yet, it fails to inhibit retroviruses that exploit m6A synthesis routes and are blocked by drugs targeting IGF2BP2 m6A reader. By deciphering the molecular fingerprint of cells treated with therapies targeting translation we identify a rational approach to select broad-spectrum antivirals with potential to counteract future pandemic viruses.

To rationalize possible combinations, the efficacy in the Gata1low model of drugs currently used for these patients (the JAK1/2 inhibitor Ruxolitinib) was compared with that of drugs targeting other abnormalities, such as p27kip1 (Aplidin), TGF-β (SB431542, inhibiting ALK5 downstream to transforming growth factor beta (TGF-β) signaling and TGF-β trap AVID200), P-selectin (RB40.34), and CXCL1 (Reparixin, inhibiting the CXCL1 receptors CXCR1/2). None of the drugs reduced osteopetrosis. These results suggest that future therapies for myelofibrosis should consider combining JAK1/2 inhibitors with drugs targeting hematopoietic stem cells (p27Kip1) or the pro-inflammatory milieu (TGF-β or CXCL1).

Among them, plitidepsin was approved for the treatment of multiple myeloma whereas metarrestin was currently under clinical development. Despite significant achievements in these two interrelated fields, hitherto there lacks a systematic examination of the eEF1A protein in the context of cancer research. Therefore, the present work aims to delineate its clinical implications, molecular oncogenic mechanisms, and targeted therapeutic strategies as reflected in the ever expanding body of literature, so as to deepen mechanistic understanding of eEF1A-involved tumorigenesis and inspire the development of eEF1A-targeted chemotherapeutics and biologics.

However, despite the massive increase in the number of marine natural products classified as 'anticancer leads,' most of which correspond to general cytotoxic agents, and only a few have been characterized regarding their molecular targets and mechanisms of action. The current review presents a critical analysis of inhibitors of HIF-1 and HIF-2 and hypoxia-selective compounds that have been sourced from marine organisms and that might act as new chemotherapeutic candidates or serve as templates for the development of structurally similar derivatives with improved anticancer efficacy.

P2, N=37, Terminated, PharmaMar | N=150 --> 37 | Active, not recruiting --> Terminated; Significant difficulties in the recruitment of patients

P2, N=150, Active, not recruiting, PharmaMar | Recruiting --> Active, not recruiting | Trial completion date: Jul 2025 --> Apr 2024 | Trial primary completion date: Jun 2025 --> Mar 2024

P2, N=150, Recruiting, PharmaMar

EEF1A2 exhibits angiogenic potential in both normoxic and hypoxic conditions, underscoring its dual role in promoting EMT and angiogenesis, rendering it a promising target for cancer therapy.

P2, N=150, Recruiting, PharmaMar | Trial completion date: Aug 2024 --> Jul 2025 | Trial primary completion date: Jul 2024 --> Jun 2025

Sixty percent (3/5) had received 6 cycles of obitunuzumab and bendamustine (the last dose in patients 1 and 2 were administered 2 years prior to admission). Patients 2 and 5 had received rituximab maintenance, the last dose being administered in both < 2 months prior to admission for SARS-CoV-2. Patient 3 had received 6 cycles of obinutuzumab-COMP and maintenance with obinutuzumab, with the last dose administered 9 months before admission for SARS-COV-2... Plitidepsin shows a good safety profile in patients with NHL and SARS-CoV-2 infection. Four of the 5 patients presented resolution of SARS-CoV-2 infection. Prospective studies are needed to confirm the effectiveness of plitidepsin as a treatment for SARS-CoV-2 infection in patients with NHL who have received immunochemotherapy.

These data support plitidepsin as a well-tolerated treatment that might have potential clinical and antiviral efficacy in COVID-19 immunocompromised patients.