From in silico target prediction to multi-target drug design: Current databases, methods and applications

2011 ◽  
Vol 74 (12) ◽  
pp. 2554-2574 ◽  
Author(s):  
Alexios Koutsoukas ◽  
Benjamin Simms ◽  
Johannes Kirchmair ◽  
Peter J. Bond ◽  
Alan V. Whitmore ◽  
...  
Keyword(s):  
Drug Design ◽  
In Silico ◽  
Target Prediction ◽  
Target Drug

Combination Vs. Multi-target drugs: The Clash of the titans in the arena of drug discovery; An overview and in silico evaluation

2021 ◽  
pp. 4455-4462
Author(s):  
Rohan Mishra ◽  
Aneesh T P
Keyword(s):  
Drug Design ◽  
In Silico ◽  
Fixed Dose ◽  
The Past ◽  
Target Drug ◽  
Single Pill ◽  
Development Processes ◽  
Potent Drug ◽  
New Perspective ◽  
Targeted Approach

Over the last few decades, either the single-pill therapy or the combinations of pill therapy were at the cutting edge in drug design and development processes, which not only proved to have treated innumerable complications but also have proved its drastic need in the past and even in the present watch. This review has a briefing on the comparison of the different aspects of prescriptions as polypharmacy, combination therapy along with multi targets drugs. As the time passed, the need for an alternative to overcome the several possible ill-effects like drug-drug interaction, non-adherence, fixed-dose medications for all patients, etc., also have paved the way to showcase the in-efficiency in treating the complex nexus cascade that has raised a thought amongst for a newer brand new perspective to take a turn and transmute the concept of drug design. From a single targeted therapy to a multi-targeted approach in this drug design pattern. It also mentions the colligation of different pharmacophores entities to obtain a better potent drug with better ADMET. An overview of how 'efficient, relevant, and important multi-target drug therapy would be over a combination of pills' further have been sketched and depicted based on past prototype examples and present scenarios. The feasibility of the concept was investigated by an in silico approach where a colligated molecule of tranexamic acid and Meloxicam was analysed for its binding affinity towards the parent receptors. The newly designed, the colligated molecule was found to be more active than the parent drugs to multiple targets. The evaluation of the concept leads to a new horizon of MTD, which can be adopted through several approaches, including the colligation of the already existing drugs.

Identification of BAP1-associated MicroRNAs and Implications in Cancer Development

2019 ◽  
pp. 1-4
Author(s):  
Tikam Chand ◽  
Tikam Chand
Keyword(s):  
Gene Regulation ◽  
In Silico ◽  
Mirna Target ◽  
Target Prediction ◽  
Differential Regulation ◽  
Cancer Development ◽  
Mirna Target Prediction ◽  
Cancer Types ◽  
In Silico Tools

Having role in gene regulation and silencing, miRNAs have been implicated in development and progression of a number of diseases, including cancer. Herein, I present potential miRNAs associated with BAP1 gene identified using in-silico tools such as TargetScan and Exiqon miRNA Target Prediction. I identified fifteen highly conserved miRNA (hsa-miR-423-5p, hsa-miR-3184-5p, hsa-miR-4319, hsa-miR125b-5p, hsa-miR-125a-5p, hsa-miR-6893-3p, hsa-miR-200b-3p, hsa-miR-200c-3p, hsa-miR-505-3p.1, hsa-miR-429, hsa-miR-370-3p, hsa-miR-125a-5p, hsa-miR-141-3p, hsa-miR-200a-3p, and hsa-miR-429) associated with BAP1 gene. We also predicted the differential regulation of these twelve miRNAs in different cancer types.

Phytochemicals for drug discovery in Alzheimer’s disease: In silico Advances

2020 ◽  
Vol 26 ◽  
Author(s):  
Smriti Sharma ◽  
Vinayak Bhatia
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Drug Design ◽  
In Silico ◽  
Drug Targets ◽  
Development Process ◽  
Phytochemical Analysis ◽  
Computational Drug Design ◽  
Novel Drugs ◽  
Game Changer

: The search for novel drugs that can prevent or control Alzheimer’s disease has attracted lot of attention from researchers across the globe. Phytochemicals are increasingly being used to provide scaffolds to design drugs for AD. In silico techniques, have proven to be a game-changer in this drug design and development process. In this review, the authors have focussed on current advances in the field of in silico medicine, applied to phytochemicals, to discover novel drugs to prevent or cure AD. After giving a brief context of the etiology and available drug targets for AD, authors have discussed the latest advances and techniques in computational drug design of AD from phytochemicals. Some of the prototypical studies in this area are discussed in detail. In silico phytochemical analysis is a tool of choice for researchers all across the globe and helps integrate chemical biology with drug design.

Appraisal of the role of In silico Methods in Pyrazole based drug design

2020 ◽  
Vol 20 ◽  
Author(s):  
Smriti Sharma ◽  
Vinayak Bhatia
Keyword(s):  
Drug Design ◽  
In Silico ◽  
Md Simulations ◽  
Quantitative Structure Activity Relationship ◽  
Field Analysis ◽  
Computational Techniques ◽  
Neuroprotective Drugs ◽  
Pharmacological Potential ◽  
Available Information ◽  
Anti Fungal

: Pyrazole and its derivatives are a pharmacologically significant active scaffold that have innumerable physiological and pharmacological activities. They can be very good targets for the discovery of novel anti-bacterial, anticancer, anti-inflammatory, anti-fungal, anti-tubercular, antiviral, antioxidant, antidepressant, anti-convulsant and neuroprotective drugs. This review focuses on the importance of in silico manipulations of pyrazole and its derivatives for medicinal chemistry. The authors have discussed currently available information on the use of computational techniques like molecular docking, structure-based virtual screening (SBVS), molecular dynamics (MD) simulations, quantitative structure activity relationship (QSAR), comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) to drug design using pyrazole moieties. Pyrazole based drug design is mainly dependent on the integration of experimental and computational approaches. The authors feel that more studies need to be done to fully explore the pharmacological potential of the pyrazole moiety and in silico method can be of great help.

Drug repurposing using similarity-based target prediction, docking studies and scaffold hopping of lefamulin

2020 ◽  
Vol 17 ◽  
Author(s):  
Shikha Sharma ◽  
Shweta Sharma ◽  
Vaishali Pathak ◽  
Parwinder Kaur ◽  
Rajesh Kumar Singh
Keyword(s):  
In Silico ◽  
Target Prediction ◽  
Drug Repurposing ◽  
Docking Studies ◽  
Target Protein ◽  
Future Perspective ◽  
Antibacterial Drug ◽  
Scaffold Hopping ◽  
Target Proteins ◽  
Renin Inhibitors

Aim: To investigate and validate the potential target proteins for drug repurposing of newly FDA approved antibacterial drug. Background: Drug repurposing is the process of assigning indications for drugs other than the one(s) that they were initially developed for. Discovery of entirely new indications from already approved drugs is highly lucrative as it minimizes the pipeline of the drug development process by reducing time and cost. In silico driven technologies made it possible to analyze molecules for different target proteins which are not yet explored. Objective: To analyze possible targets proteins for drug repurposing of lefamulin and their validation. Also, in silico prediction of novel scaffolds from lefamulin has been performed for assisting medicinal chemists in future drug design. Methods: A similarity-based prediction tool was employed for predicting target protein and further investigated using docking studies on PDB ID: 2V16. Besides, various in silico tools were employed for prediction of novel scaffolds from lefamulin using scaffold hopping technique followed by evaluation with various in silico parameters viz., ADME, synthetic accessibility and PAINS. Results: Based on the similarity and target prediction studies, renin is found as the most probable target protein for lefamulin. Further, validation studies using docking of lefamulin revealed the significant interactions of lefamulin with the binding pocket of the target protein. Also, three novel scaffolds were predicted using scaffold hopping technique and found to be in the limit to reduce the chances of drug failure in the physiological system during the last stage approval process. Conclusion: To encapsulate the future perspective, lefamulin may assist in the development of the renin inhibitors and, also three possible novel scaffolds with good pharmacokinetic profile can be developed into both as renin inhibitors and for bacterial infections.

In Silico Study of Potential Cross-Kingdom Plant MicroRNA Based Regulation in Chronic Myeloid Leukemia

2020 ◽  
Vol 17 (2) ◽  
pp. 125-132
Author(s):  
Marjanu Hikmah Elias ◽  
Noraziah Nordin ◽  
Nazefah Abdul Hamid
Keyword(s):  
Targeted Therapy ◽  
In Silico ◽  
Structure Prediction ◽  
Tertiary Structure ◽  
Target Prediction ◽  
In Silico Analysis ◽  
Microrna Target ◽  
Good Target

Background: Chronic Myeloid Leukaemia (CML) is associated with the BCRABL1 gene, which plays a central role in the pathogenesis of CML. Thus, it is crucial to suppress the expression of BCR-ABL1 in the treatment of CML. MicroRNA is known to be a gene expression regulator and is thus a good candidate for molecularly targeted therapy for CML. Objective: This study aims to identify the microRNAs from edible plants targeting the 3’ Untranslated Region (3’UTR) of BCR-ABL1. Methods: In this in silico analysis, the sequence of 3’UTR of BCR-ABL1 was obtained from Ensembl Genome Browser. PsRNATarget Analysis Server and MicroRNA Target Prediction (miRTar) Server were used to identify miRNAs that have binding conformity with 3’UTR of BCR-ABL1. The MiRBase database was used to validate the species of plants expressing the miRNAs. The RNAfold web server and RNA COMPOSER were used for secondary and tertiary structure prediction, respectively. Results: In silico analyses revealed that cpa-miR8154, csi-miR3952, gma-miR4414-5p, mdm-miR482c, osa-miR1858a and osa-miR1858b show binding conformity with strong molecular interaction towards 3’UTR region of BCR-ABL1. However, only cpa-miR- 8154, osa-miR-1858a and osa-miR-1858b showed good target site accessibility. Conclusion: It is predicted that these microRNAs post-transcriptionally inhibit the BCRABL1 gene and thus could be a potential molecular targeted therapy for CML. However, further studies involving in vitro, in vivo and functional analyses need to be carried out to determine the ability of these miRNAs to form the basis for targeted therapy for CML.

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