Monoclonal antibodies work well for extracellular or cell surface-bound target antigens. Inside the membrane, though, small molecules with favorable pharmacological properties (e.g., Lipinski’s Rule of 5) are preferred.
That paradigm could change thanks to smaller antibodies (“nanobodies”) conjugated to cell penetrating peptides, as shown by Herce et al. (2017) in “Cell-permeable nanobodies for targeted immunolabelling and antigen manipulation in living cells.”
Coupled with new, well-named methods like AdPROM (Affinity-directed Protein Missiles) that mediate the “orderly” proteasomal degradation of targets, we may be opening a new chapter in pharmacology.
Also see: Phys.com, “Researchers report on cell-permeable nanobodies” 2017.