Bioisosteres are useful sets of tools for medicinal chemistry so as to endow a hit or the lead to possess the requisite pharmacokinetic and pharmacodynamic property with high activity and selectivity. As discussed in our blog,1) bioisosteres of prevalent chemical structures are still developing. However, it is often the case with a medicinal chemist to...

Structure-based drug design (SBDD) is a rational and reasonable way for the creation of more feasible and acceptable molecules to the target protein of interest. Generative AI is changing our way of life, and it has a huge impact on scientists and researchers. Recent development of generative AI-mediated structure-based computational design is opening the utilization...

Prediction and selection of a ligand binding mode with high accuracy is still a difficult challenge in molecular docking even in this age of high computational capacity. Numerous challenges have been performed for over a century due to the overwhelming demand for protein-ligand complex in drug discovery. Induced fit is one of the intriguing but...

Switching a problematic functional group to a surrogate bioisostere is a powerful strategy for pharmacophore-based lead generation and optimization. Carboxylic acids,1),2) peptide bonds,3) amines as well as aromatic rings including phenols and indoles often displays crucial role as the constituents of pharmacophores. However, a severe struggle would arise when the key functional group possesses undesirable...

Data is essential for decision making and its importance is expanding after the emergence of artificial intelligence (AI)-based technologies and methods. Even before the advent of AI, statistical analysis of real data has been widely performed to support the humans’ predictions. In the field of healthcare, however, data collection encounters the challenges of privacy due...

Innovation in technology have brought about paradigm shifts in pharmaceutical science. The landscape of pharmaceutical industry has changed its appearance over the decades, driven by the necessity to adapt itself to consumer expectation, regulatory forces and demographic shifts. It is substantially required for pharma to keep themselves updated and adjusted to the upcoming era so...

TIDES (peptides and nucleotides) is seeing the light of the day. TIDES gained an intense attention in drug discovery and the number of the approved TIDES by FDA rose up to nine in 2023.1) The molecular entity covers 16% of the approved drugs and it is expanding the realm over the couple of years.2) Still,...

Natural products often have significant biological activity and they have been taken as the pool of drug seeds for long. In order to lead natural products druggable, they were sometimes elaborated and derivatized to increase the PK/PD profile and decrease the toxicity. These synthesized compounds are, so to say, “natural product mimetics”. PepMetics® molecules are,...

Protein function is modulated not only by competitive inhibition but also by allosteric control. The natural ligand binding site has long been targeted because the mechanism of action is clear and the assay development is relatively easy for the directly targeting drugs. Allosteric modulator of a target protein is serendipitously emerged, but now it is...

Cyclic peptides gather interests of many pharmaceutical companies due to the known high potency against various protein targets. The conformationally restricted structure with three-dimensional architecture has enabled us to target proteins called undruggable so far. There are still scarce number of cyclic peptide drug in the market but the number is increasing in this century.1)...