Designing Novel Lenalidomide Derivatives as Inhibitors of IKZF1-3 Transcription Factors Targeting CRL4CRBN E3 Ubiquitin Ligase Complex

Cancer continues to pose a significant threat to global health despite extensive research, clinical trials, and therapeutic interventions. The emergence of targeted therapies has brought hope to the field, with lenalidomide standing out as a promising treatment option for hematological malignancies. Lenalidomide, an immune-modulating drug, exhibits potent anti-cancer, anti-angiogenic, and anti-inflammatory properties. As research advances, there is a growing focus on designing novel drug compounds to combat cancer effectively. Immunomodulatory drugs (IMiDs), including lenalidomide, target the CRL4CRBN E3 ubiquitin ligase complex and facilitate the ubiquitination of transcription factors Ikaros and Aiolos (IKZF1 and IKZF3). This article aimed to compare lenalidomide's performance with the newly designed analog LENO54 in terms of its interactions with the CRBN protein and its ability to bind to Ikaros and Aiolos transcription factors through molecular docking. Molecular docking analysis revealed that the novel analog LENO54 demonstrated significantly lower binding energy and higher inhibitory capacity compared to lenalidomide. These findings suggest that LENO54 may hold greater promise as an anti-tumor agent, particularly for patients diagnosed with multiple myeloma. In conclusion, this study highlights the potential of LENO54 as a superior therapeutic candidate, shedding light on the importance of continued research in developing targeted therapies for cancer treatment.