samhd1

TH7127 is a selective inhibitor of the sterile alpha motif and histidine-aspartate domain-containing protein-1 (SAMHD1), inhibits hydrolysis of ara-CTP and Cl-F-ara-ATP, and inhibits the enzymatic activity of SAMHD1 on dGTP, Cl-F-ara-ATP, and ara-CTP.

Sp-2'-Deoxycytidine-5'-O-(1-thiotriphosphate) (Sp-dCTP-α-S), an isomer of the sulfur-containing nucleotide derivative dCTP-α-S, functions as an inhibitor of the deoxynucleoside triphosphate triphosphohydrolase SAMHD1, with an inhibition constant (Ki) of 6.3 µM.

Rp-dGTPαS, an enantiomer of the dNTPαS nucleotide, serves as the substrate for SAMHD1, a critical regulator of cellular dNTP levels that curtails the replication of viruses (HIV-1, etc.) in CD4+ myeloid lineage and resting T cells. The SAMHD1 tetrameric complex facilitates the hydrolysis of Rp-dGQTPαS into 2'-deoxynucleosides and triphosphates [1].

Sp-TTPαS is a competitive inhibitor of the catalytic activity of sterile alpha motif and HD domain containing protein 1 (SAMHD1). It competitively inhibits TTP hydrolysis, with a Ki value of 46 µM.

Sp-2'-Deoxyguanosine-5'-O-(1-thiotriphosphate), a sulfur-containing isomer of 2'-deoxyguanosine-5'-O-triphosphate (dGTP), functions as an inhibitor of the deoxynucleoside triphosphate triphosphohydrolase SAMHD1, with an inhibitory constant (Ki) of 820 nM.

Sp-Thymidine-5'-O-(1-thiotriphosphate) (Sp-TTP-α-S), an isomer of the sulfur-containing nucleotide derivative TTP-α-S, exhibits affinity for HIV-1 reverse transcriptase with dissociation constants (Kds) of 2.88, 4.23, and 20.21 µM in the presence of magnesium, manganate, and cobalt, respectively. Additionally, Sp-TTP-α-S effectively inhibits the enzyme deoxynucleoside triphosphate triphosphohydrolase SAMHD1 with an inhibition constant (Ki) of 46 nM.

Cephalosporin C zinc salt was a potent inhibitor of SAMHD1 (IC50 : 1.1 ± 0.1 µM), and this inhibition was largely attributable to the presence of zinc.