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Hck-IN-1 (compound B9), a diphenylpyrazolo compound, is a selective Nef-dependent Hck inhibitor with IC₅₀s of 2.8 μM, >20 μM for Nef:Hck complex and Hck, respectively. Hck-IN-1 is a direct and wide HIV-1 Nef antagonists with an IC₅₀ of 100-300 nM for wild-type HIV-1 replication. Hck-IN-1 binds pocket residue Asn126 and has anti-retroviral activity.

Hck-IN-1 (compound B9) shows weak activity against other Src-family members in vitro, with IC₅₀ values >20 μM for c-Src, Lck and Lyn.
B9 (1 μM; 8 days) completely inhibits Nef-dependent SFK activation at a concentration of 1.0 μM.
Hck-IN-1 (0.1, 0.3, 1, 3 μM) also inhibits Nef-mediated enhancement of HIV-1 infectivity in a concentration-dependent manner in the reporter cell line, TZM-bl.
Hck-IN-1 inhibits the replication of all eleven HIV-1 Nef chimeras with IC₅₀ values of ~ 300 nM in CEM-T4 cells, demonstrating that the compound is broadly active against HIV replication supported by a wide range of HIV-1 Nef proteins.

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