AN UNDERGRADUATE SEMINAR

PRESENTATIONOn

The Roles Of Bioinformatics in the Drug Discovery Process

Department of Biochemistry, Faculty of Life Sciences,

University of Ilorin, March 2015.

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05/03/2023 10:16:56 AMDepartment of Biochemistry, Faculty of Life Sciences, University of Ilorin, Ilorin.

THE ROLES OF BIOINFORMATICS IN

THE DRUG DISCOVERY PROCESSPresented

By

ADEBOWALE, Qazeem Omotola

11/55EH018

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05/03/2023 10:16:56 AMDepartment of Biochemistry, Faculty of Life Sciences, University of Ilorin, Ilorin.

05/03/2023 10:16:56 AM

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OUTLINES

IntroductionThe Drug Discovery Applications of Bioinformatics in The drug Discovery ProcessConclusion

Department of Biochemistry, Faculty of Life Sciences, University of Ilorin, Ilorin.

05/03/2023 10:16:56 AM Department of Biochemistry, Faculty of Life Sciences, University of Ilorin, Ilorin.

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Definition of BioinformaticsAs defined by National Center for Biotechnology Information (2001).As defined by Lopresti (2008).

Aims of BioinformaticsTo Store and arrange,To analyze,To interpret vast amount of large data

INTRODUCTION

05/03/2023 10:16:57 AM Department of Biochemistry, Faculty of Life Sciences, University of Ilorin, Ilorin.

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Figure 1: Illustrating the definition of bioinformatics (Lopresti, 2008).

INTRODUCTION (Contd.)

05/03/2023 10:16:57 AM Department of Biochemistry, Faculty of Life Sciences, University of Ilorin, Ilorin.

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THE DRUG DISCOVERYWhat is Drug?

In pharmacology, Drug is any chemical agent that alters the biochemical or physiological processes of tissues or organisms (United Nations Office Drug and Crime, 2015 ).

05/03/2023 10:16:57 AM Department of Biochemistry, Faculty of Life Sciences, University of Ilorin, Ilorin.

Definition of drug discovery

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THE DRUG DISCOVERY PROCESS

05/03/2023 10:16:57 AM Department of Biochemistry, Faculty of Life Sciences, University of Ilorin, Ilorin.

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THE DRUG DISCOVERY PROCESSDeveloping a new drug (figure 2) is

Lengthy (Ibekwe and Ameh, 2014),RiskyIt involves a number of processes, that are very expensive, figure 3, (Bie et al, 2015).

05/03/2023 10:16:57 AM Department of Biochemistry, Faculty of Life Sciences, University of Ilorin, Ilorin.

Review and approval by Food & Drug Administration

1 compound approved

Phase III: Confirms effectiveness and monitors adverse reactions from long-term use in 1,000 to5,000 patient volunteers.

Phase II: Assesses effectiveness and looks for side effects in 100 to 500 patient volunteers.

Phase I: Evaluates safety and dosage in 20 to 100 healthy human volunteers.

5 compounds enter clinical trials

Discovery and preclininal testing: Compounds are identified and evaluated in laboratory and animal studies for safety, biological activity, and formulation.

5,000 compounds evaluated

0 2 4 6 8 10 12 14 Years 16

Figure 2 : how risky and lengthy traditional drug discovery is (Source: Tufts Center for the Study of Drug Development)

05/03/2023 10:16:57 AM Department of Biochemistry, Faculty of Life Sciences, University of Ilorin, Ilorin.

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S Figure 3 : How expensive the traditional drug discovery is (Jayaram et al.)

05/03/2023 10:16:57 AM Department of Biochemistry, Faculty of Life Sciences, University of Ilorin, Ilorin.

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Stages involve in the discovery of drugs (figure 4)

05/03/2023 10:16:57 AM Department of Biochemistry, Faculty of Life Sciences, University of Ilorin, Ilorin.

Drug Discovery & DevelopmentIdentify disease

Isolate proteininvolved in disease (2-5 years)

Find a drug effectiveagainst disease protein(2-5 years)

Preclinical testing(1-3 years)

Human clinical trials(2-10 years)

FDA approval(2-3 years)

Lead

op

timiz

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Figure 4: Illustrating the stages of drug discovery process (according to Tenthoff, 2006)

05/03/2023 10:16:57 AM Department of Biochemistry, Faculty of Life Sciences, University of Ilorin, Ilorin.

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APPLICATION OF BIOINFORMATICS IN

THE DRUG DISCOVERY PROCESS

05/03/2023 10:16:57 AM Department of Biochemistry, Faculty of Life Sciences, University of Ilorin, Ilorin.

The application of bioinformatics cut across all the process of drug discovery, thereby

Reducing the risk of drug failureMaking it a bit cheaperReducing the time spent in the discoveryAnd also automates the entire process, thereby reducing human intervention.

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ROLES OF BIOINFORMATICS IN THE DRUG DISCOVERY PROCESS

05/03/2023 10:16:57 AM Department of Biochemistry, Faculty of Life Sciences, University of Ilorin, Ilorin.

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APPLICATIONS OF THE DRUG DISCOVERY PROCESS

IN TARGET IDENTIFICATION:

One need to know about the molecular bases of the disease

Bioinformatics method have been used to virtually screen target for compound that binds and inhibit the protein (Searls , 2000).

05/03/2023 10:16:58 AM Department of Biochemistry, Faculty of Life Sciences, University of Ilorin, Ilorin.

IN TARGET VALIDATIONA target needs to be evaluated to ensure that modulation of the target, will have desired therapeutic effect.

This process can be accelerated with bioinformatics tools, therefore speeds up target validation step significantly (searls , 2000).

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APPLICATIONS OF THE DRUG DISCOVERY PROCESS

05/03/2023 10:16:58 AM Department of Biochemistry, Faculty of Life Sciences, University of Ilorin, Ilorin.

IN LEAD IDENTIFICATIONHigh throughput screening is a major strategy for the discovery of new leads (Evans 2009).

With Bioinformatics, protein targets are screened against database of small molecule compounds, to see which molecule binds strongly to the targets.

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05/03/2023 10:16:58 AM Department of Biochemistry, Faculty of Life Sciences, University of Ilorin, Ilorin.

IN LEAD OPTIMIZATIONThe computational technique used in refining the structure of lead compound is QSAR - Quantity Structure Activity Relationship (Roa and Srinivas 2011).

The information from QSAR can be used to suggests new chemical modifications for synthesis and testing (Roa and Srinivas 2011).

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05/03/2023 10:16:58 AM Department of Biochemistry, Faculty of Life Sciences, University of Ilorin, Ilorin.

IN PRE CLINICAL TESTINGTest is done with or without the use of animalsPurpose: To limit the risk of novel drugsPreclinical testing involves:Pharmacology,Toxicology,Pharmacokinetics, etc. (Roa and Srinivas 2011).

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05/03/2023 10:16:58 AM Department of Biochemistry, Faculty of Life Sciences, University of Ilorin, Ilorin.

ROLES IN CLINICAL TRIALS The bioavailability and bioactivity of drugs are: absorption, distribution, metabolism, excretion, toxicity (ADMET) and efficacy (Roa and Srinivas 2011).

Although these properties are usually measured in the lab, they can also be predicted in advance with bioinformatics such as C2-ADME, TOPKAT, CLOGP, DrugMatrix, AbSolv, Bioprint, GastroPlus (Roa and Srinivas 2011).

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Identify disease

Isolate protein

Find drug

Preclinical testing

GENOMICS, PROTEOMICS & BIOPHARM.

HIGH THROUGHPUT SCREENING

MOLECULAR MODELING

VIRTUAL SCREENING

COMBINATORIAL CHEMISTRY

IN VITRO & IN SILICO ADME MODELS

Potentially producing many more targetsand “personalized” targets

Screening up to 100,000 compounds aday for activity against a target protein

Using a computer topredict activity

Rapidly producing vast numbersof compounds

Computer graphics & models help improve activity

Tissue and computer models begin to replace animal testing

Figure 5 : Summary of the application of bioinformatics in the drug discovery process (According to Searls , 2000).

05/03/2023 10:16:58 AM Department of Biochemistry, Faculty of Life Sciences, University of Ilorin, Ilorin.

The drug discovery and development process is a long and expensive one. It starts from target identification, to Clinical trials before it is being approved.

Therefore before any newly discovered drug is placed on the market, it must undergo extreme preclinical and clinical tests and get a regulatory approval.

Due to the limitation of throughput, accuracy and cost, experimental techniques cannot be applied widely, therefore, in recent times the drug discovery process has shifted to the use of BIOINFORMATICS.

Bioinformatics approach has been of great importance to develop fast and accurate target identification and prediction method for the discovery.

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CONCLUSION

05/03/2023 10:16:58 AM Department of Biochemistry, Faculty of Life Sciences, University of Ilorin, Ilorin.

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