Elsulfavirine sodium

Elsulfavirine sodium (R-1206 sodium) is an orally effective inhibitor of human carbonic anhydrase (CA) and an allosteric inhibitor of HIV-1 non-nucleoside reverse transcriptase (NNRT). It targets and disrupts the interaction between adenylosuccinate lyase (ADSL) and insulin-induced gene proteins INSIG1/2, blocking SREBP-1-mediated de novo lipid synthesis and inhibiting liver cancer cell proliferation. In combination with Lenvatinib, Elsulfavirine sodium exhibits synergistic antitumor effects. Inside the body, it converts to the active metabolite VM1500A, which blocks reverse transcriptase DNA polymerization activity, thereby inhibiting HIV-1 replication. The Ki values for Elsulfavirine sodium against human carbonic anhydrase subtypes I, VII, VI, VA, VB, IX, XIII, XIV range from 1960 nM to 52400 nM. This compound is utilized in research related to HIV-1 infection and liver cancer.

CA I (human):52400 nM (Ki)

Elsulfavirine (10 μM; 1 h) sodium significantly inhibits the interaction between ADSL and INSIG1/2 in high-glucose-induced Huh7 cells, suppresses the cleavage activation and nuclear translocation of SREBP-1, blocks SRE-driven luciferase transcription activity, and prevents activation of the SREBP lipid synthesis pathway. Elsulfavirine (10 μM; 12 h) sodium effectively reduces the transport of SCAP from the endoplasmic reticulum to the Golgi in high-glucose-induced Huh7 cells, downregulates mRNA expression levels of SREBP-1 downstream lipogenic target genes FASN, ACACA, SCD, and GPAM, decreases intracellular lipid droplet accumulation, and inhibits lipid storage induced by high glucose. Elsulfavirine (10 μM; 8 h) sodium markedly blocks the conversion of 14 C-glucose into triglycerides and fatty acids in Huh7 cells, thereby inhibiting de novo lipogenesis. The active metabolite of Elsulfavirine, VM-1500A (serum-adjusted EC50 approximately 13.8 nM), effectively inhibits replication of HIV-1 clinical isolates in in vitro cell models.

Elsulfavirine sodium (10 mg/kg; oral administration; once daily; for 20 days) significantly inhibits liver cancer tumor growth in a subcutaneous xenograft model with Huh7 cells in nude mice. It reduces the expression of the proliferation marker Ki-67 in tumor tissues, enhances tumor cell apoptosis, and downregulates the protein expression of SREBP-1, FASN, and ACLY. When combined with Lenvatinib (administered similarly to Elsulfavirine), Elsulfavirine sodium further synergizes to suppress liver cancer tumor growth in the same model, proving more effective than the use of a single agent.