ddhCTP trisodium solution (100 mM ± 3 mM)

ddhCTP trisodium solution (100 mM ± 3 mM) is an endogenously produced pyrimidine base analog with a K d of 17.0 nM for LLDH and an IC₅₀ of 55.8 μM for GAPDH. By inhibiting key metabolic enzymes such as GAPDH, ddhCTP trisodium reduces glycolytic flux and shifts metabolic flow toward the pentose phosphate pathway, thereby regulating the redox balance of cells. As a competitive CTP analog, ddhCTP trisodium terminates RNA synthesis by flavivirus RdRps and SARS-CoV-2 RdRp, and inhibits Zika virus replication in vivo. ddhCTP trisodium can be used in studies related to viral infections, COVID-19 and Zika virus infections ^{[1] [2]}.

In Vitro, ddhCTP (24-96 h) trisodium completely abolishes the extracellular levels of phenylacetic acid and 4-hydroxyphenyllactic acid in HEK293 cells expressing wild-type RSAD2^[1]. ddhCTP (72 h) trisodium modulates the levels of NAD+-dependent enzyme-related metabolites, including decreased taurine levels, increased 2-oxoglutarate levels, increased glyceraldehyde 3-phosphate levels, and increased levels of pentose phosphate pathway intermediates in hiPSC-derived macrophages expressing wild-type RSAD2 after stimulation with LPS and IFN-γ^[1]. ddhCTP trisodium inhibits the NAD+-dependent forward activity of purified rabbit muscle GAPDH with an IC₅₀ of 55.8 μM, but does not affect the NADH-dependent reverse reaction^[1]. ddhCTP (72 μM, 30 s) trisodium inhibits the NAD+-dependent activities of purified rabbit muscle LLDH and purified bovine heart MDH, but does not affect the NADH-dependent reverse reaction of LLDH^[1].

References:
[1]. Honarmand Ebrahimi K, et al. ddhCTP produced by the radical-SAM activity of RSAD2 (viperin) inhibits the NAD+ -dependent activity of enzymes to modulate metabolism. FEBS Lett. 2020;594(10):1631-1644.
[2]. Ciardullo G, et al. Viral RNA Replication Suppression of SARS-CoV-2: Atomistic Insights into Inhibition Mechanisms of RdRp Machinery by ddhCTP. J Chem Inf Model. 2024;64(5):1593-1604.