A cell-permeable diphenylpyrazolo compound that disrupts HIV accessary protein Nef dimerization (IC50 = 3uM in HEK293T cells) and prevents Nef-mediated Src family kinase Hck activation (IC50 = 2.8uM) without directly affecting the catalytic activity of c-Src, Hck, Lck, or Lyn. Shown to suppress HIV and SIV viral replication (IC50/strain/culture = 1uM/SIV deltaB670/CEM-174 and <0.3uM/HIV-1 NL4-3/CEM-T4) and infectivity, being ineffective against the replication of Nef-defective HIV-1 mutant. Molecular docking and in vitro binding studies reveal a high-affinity B9-targeting site formed at the Nef dimerization interface and a low-affinity binding site on each Nef monomer at the dimer interface periphery.
Molecular Formula:C₁₆H₁₁ClN₆O₃S
Primary Target:Nef
Solubility:DMSO
Storage and Stability:Store at 4°C under inert atmosphere. For maximum recovery of product, centrifuge the original vial prior to removing the cap.
