Resumo

ESMAEILI, Arefeh; YOOSEFIAN, Mehdi  e  MAHANI, Mohamad. Molecular Dynamics Simulation of Lenalidomide Interaction with CRBN Protein: A target for immunomodulatory Drugs. S.Afr.j.chem. (Online) [online]. 2023, vol.77, pp.157-162. ISSN 1996-840X.  https://doi.org/10.17159/0379-4350/2023/v77a20.

Lenalidomide, an immune-modulating drug, has shown promising therapeutic efficacy in treating haematological malignancies. Lenalidomide's primary target is Cereblon (CRBN), a widely expressed protein, which plays a crucial role and found in the CUL4-RBX1-DDB1-containing E3 ubiquitin ligase complex known as CRL4. The interaction between CRBN and DDB1 results the formation of a CUL4-based E3 ubiquitin ligase complex. This complex is responsible for the ubiquitination and proteasomal degradation of proteins identified by CRBN, thereby maintaining cellular homeostasis, survival, division, proliferation, and growth by eliminating non-essential or damaged proteins. Remarkably, lenalidomide exhibits selective prevention of substrate binding to CRBN through an anti-selective mechanism and directly binds to CRBN. This mechanism has been extensively linked with treating patients with multiple myeloma-related cancers. In this study, we employ molecular dynamics simulations to investigate the interaction of lenalidomide with the CRBN protein, the primary target of immunomodulatory drugs. Our results demonstrate the effective exchange of lenalidomide with its primary target.

Palavras-chave : Lenalidomide; Cereblon; Ubiquitin; Substrate; Molecular Dynamics Simulations.

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