HDAC6-IN-33 (compound 6) is a selective and irreversible HDAC6 inhibitor with an IC 50 of 193 nM. HDAC6-IN-33 shows no activity against HDAC1-4. HDAC6-IN-33 is a tight-binding HDAC6 inhibitor capable of inhibiting HDAC6 via a two-step slow-binding mechanism.