ScafBank: a public comprehensive Scaffold database to support molecular hopping

Abstract

Aim:The search for molecules whose bioactivities are similar to those of given compounds or to optimize the initial lead compounds from high throughput screening has attracted increasing interest in recent years. Our goal is to provide a publically searchable database of scaffolds out from a large collection of existing chemical molecules. Results: Although a number of in silico methods have emerged to facilitate this process, which has become known as "scaffold hopping" or "molecular hopping", there is an urgent need for a database system to provide such valuable data in the drug design field. Here we have systematically analyzed a collection of commercially available small molecule databases and a bioactive compound database to identify unique scaffolds and we have built apublically searchable database. The analysis of approximately 4 800 000 of these compounds identified 241 824 unique scaffolds, which are stored in a relational database (http://202.127.30.184:8080/db.html). Each entry in the database is associated with a molecular occurrence and includes its distribution of molecular properties, such as molecular weight, logP, hydrogen bond acceptor number, hydrogen bond donor number, rotatable bond number and ring number. More importantly, for scaffolds derived from the bioactive compounds database, it also contains the original compounds and their target information. Conclusion: This Web-based database system could help researchers in the fields of medicinal and organic chemistry to design novel molecules with properties similar to the original compounds, but built on novel scaffolds.

Consensus Diversity Plots: a global diversity analysis of chemical libraries

“…Different approaches to obtain the scaffold of a molecule in a consistent manner have been reviewed elsewhere [23, 24]. In this work, the scaffolds were derived with the methodology described by Johnson and Xu.…”

SuperTarget goes quantitative: update on drug-target interactions

“…cancer ( 7 ) and infection ( 8 )], technical aspects [e.g. pharmacophores ( 9 ) or scaffold hoppers ( 10 )], side effects ( 11 ) or special metabolic pathways ( 12 ). The database STITCH is focused on the relation of >70 000 chemicals to targets from hundreds of different organisms ( 13 ).…”

Knowledge-Based Scoring Functions in Drug Design. 1. Developing a Target-Specific Method for Kinase−Ligand Interactions

“…The essential structural pattern of kinase ligands is that they usually consist of an aromatic ring which forms a conservative hydrophobic and hydrogen bond interaction with the hinge of CDK2. 38 By utilizing an in-house scaffold fragmentation program, 46 the scaffolds located at the hinge their derivatives, it is likely that their carbonyl oxygen atom can form a hydrogen bond with CDK2. This structural characteristic is consistent with the ligand volume factor results and the characteristics of the interactions of kinaseinhibitor systems.…”