TH6342 is a SAMHD1 modulator that binds to pretetrameric SAMHD1 and prevents its oligomerization and allosteric activation. SAMHD1 is a dNTP triphosphohydrolase and an HIV-1 restriction factor. SAMHD1 can limit the replication of retroviruses and DNA viruses and has antiviral effects. The inhibitory mechanism of TH6342 does not occupy the SAMHD1 nucleotide-binding pocket, gently binds the target, and functions as a chemical probe.
TH6342 (2.5, 10, 40 μM) blocks dGTP-induced SAMHD1 activation in a dose-dependent manne, without altering the stability of SAMHD1 to pronase treatment under 0.05-0.5 mM concentartion[1].
References:
[1]. Zhang SM, et al. Identification and evaluation of small-molecule inhibitors against the dNTPase SAMHD1 via a comprehensive screening funnel. iScience. 2024 Jan 13;27(2):108907.