Iversity (GNU), 501 Jinjudaero, Jinju 52828, Korea; [email protected] (S.P.); [email protected] (G.L.) Division of Veterinary Medicine, Institute of Animal Medicine, Gyeongsang National University (GNU), Jinju 52828, Korea; [email protected] Department of Bio Healthcare Huge Information (BK4 System), Investigation Institute of Life Sciences, Gyeongsang National University (GNU), Jinju 52828, Korea; [email protected] School of Cosmetics and Food Improvement, Kyungnam University, Masan 631701, Korea; [email protected] Division of Life Sciences and Applied Life Science (BK21 4), Analysis Institute of Organic Science (RINS), Gyeongsang National University (GNU), 501 Jinjudaero, Jinju 52828, Korea; [email protected] Correspondence: [email protected] (M.O.K.); [email protected] (K.W.L.); Tel.: 82557721360 (K.W.L.) These authors contributed equally.Publisher’s Note: MDPI stays neutral with Vorapaxar Data Sheet regard to jurisdictional claims in published maps and institutional affiliations.Abstract: The cyclindependent kinase 7 (CDK7) plays a crucial role in regulating the cell cycle and RNA polymerasebased transcription. L-Palmitoylcarnitine Biological Activity Overexpression of this kinase is linked with various cancers in humans on account of its dual involvement in cell improvement. In addition, emerging proof has revealed that inhibiting CDK7 has anticancer effects, driving the improvement of novel and more costeffective inhibitors with enhanced selectivity for CDK7 over other CDKs. In the present investigation, a pharmacophorebased strategy was utilized to determine potential hit compounds against CDK7. The generated pharmacophore models had been validated and utilised as 3D queries to screen 55,578 all-natural druglike compounds. The obtained compounds had been then subjected to molecular docking and molecular dynamics simulations to predict their binding mode with CDK7. The molecular dynamics simulation trajectories have been subsequently employed to calculate binding affinity, revealing four hitsZINC20392430, SN00112175, SN00004718, and SN00262261having a superior binding affinity towards CDK7 than the reference inhibitors (CT7001 and THZ1). The binding mode evaluation displayed hydrogen bond interactions using the hinge area residues Met94 and Glu95, DFG motif residue Asp155, ATPbinding internet site residues Thr96, Asp97, and Gln141, and quintessential residue outside the kinase domain, Cys312 of CDK7. The in silico selectivity with the hits was additional checked by docking with CDK2, the close homolog structure of CDK7. Moreover, the detailed pharmacokinetic properties had been predicted, revealing that our hits have far better properties than established CDK7 inhibitors CT7001 and THZ1. Hence, we argue that proposed hits may possibly be crucial against CDK7related malignancies. Key phrases: CDK7; cancer; pharmacophore; molecular docking; MD simulation; MMPBSA; pharmacokinetic propertiesCopyright: 2021 by the authors. Licensee MDPI, Basel, Switzerland. This short article is an open access write-up distributed under the terms and circumstances of your Inventive Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ four.0/).1. Introduction Cancer is among the major causes of death inside the 21st century and the most essential obstruction for the upsurge of the global lifespan [1]. As a result, the pharmaceutical business and scientific communities have all focused on decreasing the cancerrelated deathBiomedicines 2021, 9, 1197. https://doi.org/10.3390/biomedicineshttps://www.mdpi.com/journal/biomedicinesBiomedicines 2021, 9,two ofrate, wi.