Multi-cavity molecular descriptor interconnections: Enhanced protocol for prediction of serum albumin drug binding.

The role of human serum albumin (HSA) in the transport of molecules predicates its involvement in the determination of drug distribution and metabolism. Optimization of ADME properties are analogous to HSA binding thus this is imperative to the drug discovery process. Currently, various in silico predictive tools exist to complement the drug discovery process, however, the prediction of possible ligand-binding sites on HSA has posed several challenges.

Talazoparib Dual-targeting on Poly (ADP-ribose) Polymerase-1 and -16 Enzymes Offers a Promising Therapeutic Strategy in Small Cell Lung Cancer Therapy: Insight from Biophysical Computations.

In recent times, inhibition of poly (ADP-ribose) polymerase (PARP) enzymes by pharmacological drugs has attracted much attention as an anticancer therapy. As reported, PARP-16 has been discovered as a novel anticancer target for small cell lung cancer, and that the inhibition of both PARP-16 and PARP-1 by talazoparib can increase the overall effectiveness of talazoparib in the SCLC treatment. In this study, we employed computational approaches to investigate the differential inhibitory potency of Talazoparib on PARP-1 and PARP-16.

Simulation Models for Prediction of Bioavailability of Medicinal Drugs-the Interface Between Experiment and Computation.

The oral drug bioavailability (BA) problems have remained inevitable over the years, impairing drug efficacy and indirectly leading to eventual human morbidity and mortality. However, some conventional lab-based methods improve drug absorption leading to enhanced BA, and the recent experimental techniques are up-and-coming. Nevertheless, some have inherent drawbacks in improving the efficacy of poorly insoluble and low impermeable drugs.

Mechanistic Insights into the Selective Dual BET and PLK1 Inhibitory Activity of a Novel Benzamide Compound in Castration-Resistant Prostrate Cancer.

Though multifactorial, BET and PLK1 proteins have been found to be key players in the oncogenic process leading to castration-resistant prostate cancer through regulation of AR and MYC-mediated transcription. Hence, dual inhibition of these proteins appears to be an auspicious approach for CRPC therapy. WNY0824 has been reported to exhibit nanomolar range inhibition as well as significant anti-proliferative activity on AR-positive CRPC cells in vitro.

Unveiling the mechanistic roles of chlorine substituted phthalazinone-based compounds containing chlorophenyl moiety towards the differential inhibition of poly (ADP-ribose) polymerase-1 in the treatment of lung cancer.

PARP-1 has become an attractive target in cancer treatment owing to its significant role in breast and ovarian cancers. The design of highly selective and effective poly (ADP ribose) polymerase-1 inhibitors has significant therapeutic advantages and has remained the core of several PARP-1-based drug discovery research. The pharmacophoric relevance of a chlorine substituent in a recent study led to the design of compounds 11c (meta-chlorophenyl) and 11d (para-chlorophenyl).

Unravelling the Mechanistic Role of Quinazolinone Pharmacophore in the Inhibitory Activity of Bis-quinazolinone Derivative on Tankyrase-1 in the Treatment of Colorectal Cancer (CRC) and Non-small Cell Lung Cancer (NSCLC): A Computational Approach.

In recent years, tankyrase inhibition has gained a great focus as an anti-cancer strategy due to their modulatory effect on WNT/β-catenin pathway implicated in many malignancies, including colorectal cancer (CRC) and non-small cell lung cancer (NSCLC). Based on the structural homology in the catalytic domain of PARP enzymes, bis-quinazolinone 5 (Cpd 5) was designed to be a potent selective tankyrase inhibitor. In this study, we employed molecular dynamics simulations and binding energy analysis to decipher the underlying mechanism of TNK-1 inhibition by Cpd 5 in comparison with a known selective tankyrase, IWR-1.

East to West not North-West: Structure-Based Mechanistic Resolution of 8-Hydroxyl Replacement and Resulting Effects on the Activities of Imidazole-Based Heme Oxygenase-1 Inhibitors.

Upregulation of Heme Oxygenase-1 (HO-1) has been widely implicated in cancer growth and chemoresistance. This explains the numerous drug discovery efforts aimed at mitigating its pro-carcinogenic roles till date. In a recent study, two selective azole-based HO-1 inhibitors (Cpd1 and Cpd2) were synthesized, which exhibited differential inhibitory potencies of ~200μm.

Investigating the Mechanistic Inhibitory Discrepancies of Novel Halogen and Alkyl Di-Substituted Oxadiazole-Based Dibenzo-Azepine-Dione Derivatives on Poly (ADP-Ribose) Polymerase-1.

Numerous studies have established the involvement of Poly (ADP-ribose) Polymerase-1 (PARP-1) in cancer presenting it as an important therapeutic target over recent years. Although homology among the PARP protein family makes selective targeting difficult, two compounds [d11 (0.939 μM) and d21 (0.