A molecular dynamics study of AZD4573 and Roscovitine as two potent inhibitors of cyclin dependent kinase 9

Hamza Siyar, Hassane Mamad, Souad Benkirane, Azlarab MASRAR

Department of Hematology, University of Mohammed V Souissi, Rabat, Morocco.

Refer this article

Hamza Siyar, Hassane Mamad, Souad Benkirane, Azlarab masrar, 2023. A molecular dynamics study of AZD 4573 and Roscovitine as two potent inhibitors of cyclin dependent kinase 9. Journal of medical pharmaceutical and allied sciences, V 12 - I 6, Pages- 6191 – 6198. Doi: https://doi.org/10.55522/jmpas.V12I6.5609.

ABSTRACT

The cyclin dependent kinase 9(CDK9) was confirmed in several malignancies, notably those brought on by the dysregulation of the transcriptional elongation and mRNA maturation processes, have made CDK9 an appealing therapeutic target. The creation of selective CDK9 inhibitors continues to be extremely difficult due to the great homology of these CDKs in the catalytic domain. In this work we present two potential inhibitors, AZD4573 and Roscovitine, to detect potential binding between these compounds and the protein. These two compounds are in different experimental phases. AZD4573 were able to establish hydrogen bond with Asn154 and Asp167 with several hydrophobic bonds in the complex formed. Using the assistance of molecular dynamics (MD) simulations, the mechanism and dynamic stability of the interaction between the investigated chemicals and CDK9 were identified. It is strongly advised to consider these drug candidates as potential treatments, and we propose conducting in vivo trials to experimentally validate our findings.

Keywords:

AZD4573, Roscovitine, Cyclin Dependent Kinase 9, RMSD.

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