In Silico docking studies of Flavopiridol and its analogues with human CDK9/CYCLINT complex

Breast cancer is a malignant disease most commonly occurring in women. Mortality is high due to the fact that breast cancer in later stages metastases to other parts of the body causing multiple carcinoma and death. Many therapeutic targets have been identified for breast cancer of whichCDK9 is emerging as target for cancerous cells due to its role in cell proliferation. CDK9 is a component of multiprotien complex P-TEFb which plays a vital role as an elongation factor for RNA pol2 mediated transcription. Down regulation of CDK9 leads to disruption of P-TEFb complex thereby inducing apoptosis. Flavopiridol is a semisynthetic compound based on an extract from an Indian tree. Flavopiridol is a nonspecific inhibitor of CDK’s showing higher selectivity towards CDK9. Flavopiridol acts by competing for ATP binding site thereby disrupting CDK9/Cyclin t complex. In addition, flavopiridol is found to work synergistically with several other compounds which act on other targets like HER2 receptor, Androgen receptor, Oestrogen receptor, etc., which are extensively studied for their role in breast cancer. In this study we focus on the molecular interactions of flavopiridol and its analogues using Insilco docking methods. The results provide convincing proof to establish that using flavopiridol and its analogues might prove beneficial in treatment of breast cancer whether as a sole drug or in combination with other drugs to work synergistically.