Nomegestrol acetate exhibits a diverse range of bioactivities, showcasing its potential as an inhibitor in multiple biological contexts. It is potent in various assays targeting different biological activities, including Schistosoma Mansoni Peroxiredoxins, AmpC Beta-Lactamase, Nrf2, GCN5L2, Histone Lysine Methyltransferase G9a, delayed death inhibitors of the malarial parasite plastid, human tyrosyl-DNA phosphodiesterase 1 (TDP1), and as an antiviral against Foot and Mouth Disease Virus, with potency values ranging from 4610.9 nM to 100000.0 nM.
Specifically, Nomegestrol acetate demonstrates antiviral activity against SARS-CoV-2. It showed moderate inhibition of cell viability in Vero E6 cells infected with SARS-CoV-2 after 72 hours of treatment, exhibiting an inhibition index of 0.6186. It also inhibited SARS-CoV-2 induced cytotoxicity by 14.66% in Caco-2 cells at a concentration of 10 µM after 48 hours. Additionally, in HRCE cells, the compound exhibited antiviral activity against the SARS-CoV-2 (USA-WA1/2020 strain) with a hit score of 0.2782 at MOI 0.4 after 96 hours. Despite these activities, its inhibition of the SARS-CoV-2 3CL-Pro protease at 20 µM was moderate, with an inhibition percentage of 11.84%. The compound was also active in VERO-6 cells with an IC50 greater than 20000.0 nM, indicating a relatively high concentration required for a significant inhibitory effect.
Furthermore, Nomegestrol acetate showed inhibition in enzymatic assays of human HDAC6 using different peptide substrates, with inhibition percentages of 41.31% and 1.72%. It also demonstrated high binding affinity towards numerous receptors and transporters in in vitro assays, with significant activities noted:
- Inhibition of rat Gabra1 with an AC50 of 2500.0 nM.
- High affinity binding to human PGR and AR with AC50 values of 3.0 nM and 20.0 nM, respectively.
- Moderate inhibition of human PDE4D with an AC50 of 14000.1 nM.
- Inhibition of human NR3C1 with an AC50 of 67.0 nM.
In summary, Nomegestrol acetate is a multi-target agent with noteworthy inhibitory and antiviral properties, making it a candidate for further investigation in various biological and therapeutic contexts..
Note: Summary generated by AI. Data source: ChEMBL 