Identification of novel inhibitors against Cyclin Dependent Kinase 9/Cyclin T1 complex as: Anti cancer agent

Abstract

Cell cycle consists of different types of phases, transition from G1, S, G2, M. Inhibition of associated CDKs like CDK9/Cyclin T1 complex, which are indirectly involved in the Cell cycle progression in the form of transcription elongation, reduces diverse diseases such as Cardiac Hypertrophy, Alzheimer's, Cancer, AIDS and Inflammation. Glide tool of the Schrodinger software has been used for performing Structure Based Virtual Screening and Docking against Drug Bank and MDPI database. The best hits were identified which go and bind in the active site of the target where ATP binds for the activity. The ADMET, MM-GBSA and DFT analysis is also done for the same. Compound 4-{4-[4-(3-aminopropoxy)phenyl]-1H-pyrazol-5-yl}-6-chlorobenzene-1,3-diol () was found to be more potent, novel and selective as an inhibitor. Hopefully compound () could be used as an anti-cancer agent for the treatment of life-threatening diseases.

Discovery of a tetrahydroisoquinoline-based CDK9-cyclin T1 protein–protein interaction inhibitor as an anti-proliferative and anti-migration agent against triple-negative breast cancer cells

“… 45 , 46 Another report described the in silico docking of drugs to the ATP site of CDK9-cyclin T1. 47 However, to our knowledge, no CDK9-cyclin T1 PPI inhibitor has yet been reported for targeting TNBC metastasis.…”

Analyzing the scaffold diversity of cyclin‐dependent kinase inhibitors and revisiting the clinical and preclinical pipeline

“…For activation of CDKs, the binding to their cyclin partner is a vital event 37 . Each CDK plays a specific role in the cellular machinery such as CDK2 cause apoptosis, CDK5 is essential in neuronal cell growth, and CDK7, 8, 9, 12 assists in the transcription process 38 . Based on their functions, there are two major types of CDKs viz.…”

“…37 Each CDK plays a specific role in the cellular machinery such as CDK2 cause apoptosis, CDK5 is essential in neuronal cell growth, and CDK7, 8, 9, 12 assists in the transcription process. 38 Based on their functions, there are two major types of CDKs viz. the cell-cycle CDKs (1,2,4,6) and noncell cycle CDKs (7,8,9,11,12); the former promoting the cell cycle, whereas later involved in the regulation of…”

Computational Drug Repurposing Resources and Approaches for Discovering Novel Antifungal Drugs against Candida albicans N-Myristoyl Transferase

“…In our survey, we are in consideration of Candida albicans NMT as a drug target for drug designing purpose. Typically molecular docking technique is performed either to searched out that how a specific ligand molecule bind to a target protein or illustrate binding interaction with the targetspecific amino acid residues either H-bonding, Hydrophobic interaction, disulfide bond formation, salt bridge, pi-pi interaction or to find out the potent compound from the available databases that can bind with the target protein [112][113][114][115][116][117][118][119] . The docking can be categorized into two key steps, the initial positioning of the ligand structure at the active site of the target protein using the docking algorithm.…”