Chirality. 2026 Aug;38(8):e70125. doi: 10.1002/chir.70125.
ABSTRACT
Pomalidomide is a 2nd-generation chiral immunomodulatory (IMiDs) drugs and have antiangiogenic activity. Despite being teratogenic, it has been shown to be effective in treating multiple myeloma. Enantioselectivity, chemical structure, and biological activity have been investigated using molecular docking. In silico docking simulations to confirm the enantioselective binding of pomalidomide to immunomodulator targets, namely, CRBN, TNF- α11, Pg G/H synthase 2, and Cadeherin-5 Protein. The protein was preprocessed using hydrogen addition, disulphide treatment, and bond order assignment. The Ligand Preparation Module was used to optimize all of the chosen ligands, and OPLS3e Forcefield was used to optimize the geometry. Site map analysis module was used to determine the top-ranked receptor binding sites for the enzymes. Molecules were docked by using Schrodinger 2020_3 software. Docking study confirms the enantioselective binding of pomalidomide to immunomodulator targets (CRBN, TNF-α_11, Pg G/H synthase 2, and Cadeherin-5 Protein). Out of all four targets S- (-) enantiomer of pomalidomide had significant binding with CRBN and TNF-α 11, while R-(+)enantiomer of pomalidomide had significant binding with Pg G/H synthase 2, and Cadeherin-5 Protein. The result suggests that, chemical interactions of S-enantiomer of pomalidomide have better binding with residues at the active site of CRBN and TNF-α 11. This concludes that S-enantiomer of pomalidomide could be a better choice for multiple myeloma therapy.
PMID:42470200 | DOI:10.1002/chir.70125