TaxKB: a knowledge base for new taxane-related drug discovery

Abstract

BackgroundTaxanes are naturally occurring compounds which belong to a powerful group of chemotherapeutic drugs with anticancer properties. Their current use, clinical efficacy, and unique mechanism of action indicate their potentiality for cancer drug discovery and development thereby promising to reduce the high economy associated with cancer worldwide. Extensive research has been carried out on taxanes with the aim to combat issues of drug resistance, side effects, limited natural supply, and also to increase the therapeutic index of these molecules. These efforts have led to the isolation of many naturally occurring compounds belonging to this family (more than 350 different kinds), and the synthesis of semisynthetic analogs of the naturally existing molecules (>500), and has also led to the characterization of many (>1000) of them. A web-based database system on clinically exploitable taxanes, providing a link between the structure and the pharmacological property of these molecules could help to reduce the druggability gap for these molecules.ResultsTaxane knowledge base (TaxKB, http://bioinfo.au-kbc.org.in/taxane/Taxkb/), is an online multi-tier relational database that currently holds data on 42 parameters of 250 natural and 503 semisynthetic analogs of taxanes. This database provides researchers with much-needed information necessary for drug development. TaxKB enables the user to search data on the structure, drug-likeness, and physicochemical properties of both natural and synthetic taxanes with a “General Search” option in addition to a “Parameter Specific Search.” It displays 2D structure and allows the user to download the 3D structure (a PDB file) of taxanes that can be viewed with any molecular visualization tool. The ultimate aim of TaxKB is to provide information on Absorption, Distribution, Metabolism, and Excretion/Toxicity (ADME/T) as well as data on bioavailability and target interaction properties of candidate anticancer taxanes, ahead of expensive clinical trials.ConclusionThis first web-based single-information portal will play a central role and help researchers to move forward in taxane-based cancer drug research.

Pharmacokinetic profiling of anticancer phytocompounds using computational approach

“…Three anticancer databases NPACT, CancerHSP, TaxKB were accessed from the provided hyperlinks (http://crdd.osdd.net/raghava/npact, http://lsp.nwsuaf.edu.cn/CancerHSP.php, and http://bioinfo.au-kbc.org.in/taxane/Taxkb) and the structures of chemical compounds were downloaded. These libraries contain 3269, 1565 and 252 molecules, respectively.…”

“…Several NP databases have been developed in recent years, many of which can be accessed freely . These libraries can act as a useful source for choosing lead molecules when examined for drug‐like properties .…”

“…Several NP databases have been developed in recent years, many of which can be accessed freely. 4,[11][12][13][14][15][16][17][18] These libraries can act as a useful source for choosing lead molecules when examined for drug-like properties. [19][20][21] The current trend in anticancer drug discovery is to screen for NPs with potential activity against known therapeutic targets to select leads for optimisation and development.…”

Recent advances in the area of plant-based anti-cancer drug discovery using computational approaches

“…Sharma et al [ 5 ] collected ~ 5000 anti-cancer phytomolecules from three open-access databases NPACT, CancerHSP [ 87 ], and TaxKB [ 88 ], which were then checked for their ADMET properties. The ADMET profiling of these compounds was done using QikProp with 13 parameters (namely Lipinski's Rule of 5, Jorgensen's Rule of 3, polar surface area, number of rotatable bonds, octanol–water partition coefficient [logP], affinity to plasma protein [logKHSA], number of likely metabolic reactions, number of reactive functional groups, number of amides, number of amines, number of acids, IC 50 for blockage across K+ channels [loghERG] and transport across blood–brain barrier [logBB]).…”

Current situation and future usage of anticancer drug databases

“…(1) Taxane knowledge base (TaxKB) [23] is a comprehensive database which collects detailed data on taxanes and their analogs and provides much-needed information for drug discovery (http://bioinfo.au-kbc.org. in/taxane/Taxkb).…”