the role of bioinformatics in the drug discovery process
TRANSCRIPT
![Page 1: The Role of Bioinformatics in The Drug Discovery Process](https://reader036.vdocuments.net/reader036/viewer/2022081521/5877efd91a28ab20088b6f67/html5/thumbnails/1.jpg)
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.
TH E
RO
LES
OF B
IOIN
FOR
MATIC
S IN
THE
DR
UG
DIS
CO
VE
RY
PR
OC
ES
S
05/03/2023 10:16:56 AMDepartment of Biochemistry, Faculty of Life Sciences, University of Ilorin, Ilorin.
![Page 2: The Role of Bioinformatics in The Drug Discovery Process](https://reader036.vdocuments.net/reader036/viewer/2022081521/5877efd91a28ab20088b6f67/html5/thumbnails/2.jpg)
THE ROLES OF BIOINFORMATICS IN
THE DRUG DISCOVERY PROCESSPresented
By
ADEBOWALE, Qazeem Omotola
11/55EH018
TH E
RO
LES
OF B
IOIN
FOR
MATIC
S IN
THE
DR
UG
DIS
CO
VE
RY
PR
OC
ES
S
05/03/2023 10:16:56 AMDepartment of Biochemistry, Faculty of Life Sciences, University of Ilorin, Ilorin.
![Page 3: The Role of Bioinformatics in The Drug Discovery Process](https://reader036.vdocuments.net/reader036/viewer/2022081521/5877efd91a28ab20088b6f67/html5/thumbnails/3.jpg)
05/03/2023 10:16:56 AM
TH E
RO
LES
OF B
IOIN
FOR
MATIC
S IN
THE
DR
UG
DIS
CO
VE
RY
PR
OC
ES
S
OUTLINES
IntroductionThe Drug Discovery Applications of Bioinformatics in The drug Discovery ProcessConclusion
Department of Biochemistry, Faculty of Life Sciences, University of Ilorin, Ilorin.
![Page 4: The Role of Bioinformatics in The Drug Discovery Process](https://reader036.vdocuments.net/reader036/viewer/2022081521/5877efd91a28ab20088b6f67/html5/thumbnails/4.jpg)
05/03/2023 10:16:56 AM Department of Biochemistry, Faculty of Life Sciences, University of Ilorin, Ilorin.
TH E
RO
LES
OF B
IOIN
FOR
MATIC
S IN
THE
DR
UG
DIS
CO
VE
RY
PR
OC
ES
S
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
![Page 5: The Role of Bioinformatics in The Drug Discovery Process](https://reader036.vdocuments.net/reader036/viewer/2022081521/5877efd91a28ab20088b6f67/html5/thumbnails/5.jpg)
05/03/2023 10:16:57 AM Department of Biochemistry, Faculty of Life Sciences, University of Ilorin, Ilorin.
TH E
RO
LES
OF B
IOIN
FOR
MATIC
S IN
THE
DR
UG
DIS
CO
VE
RY
PR
OC
ES
S
Figure 1: Illustrating the definition of bioinformatics (Lopresti, 2008).
INTRODUCTION (Contd.)
![Page 6: The Role of Bioinformatics in The Drug Discovery Process](https://reader036.vdocuments.net/reader036/viewer/2022081521/5877efd91a28ab20088b6f67/html5/thumbnails/6.jpg)
05/03/2023 10:16:57 AM Department of Biochemistry, Faculty of Life Sciences, University of Ilorin, Ilorin.
TH E
RO
LES
OF B
IOIN
FOR
MATIC
S IN
THE
DR
UG
DIS
CO
VE
RY
PR
OC
ES
S
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 ).
![Page 7: The Role of Bioinformatics in The Drug Discovery Process](https://reader036.vdocuments.net/reader036/viewer/2022081521/5877efd91a28ab20088b6f67/html5/thumbnails/7.jpg)
05/03/2023 10:16:57 AM Department of Biochemistry, Faculty of Life Sciences, University of Ilorin, Ilorin.
Definition of drug discovery
TH E
RO
LES
OF B
IOIN
FOR
MATIC
S IN
THE
DR
UG
DIS
CO
VE
RY
PR
OC
ES
S
THE DRUG DISCOVERY PROCESS
![Page 8: The Role of Bioinformatics in The Drug Discovery Process](https://reader036.vdocuments.net/reader036/viewer/2022081521/5877efd91a28ab20088b6f67/html5/thumbnails/8.jpg)
05/03/2023 10:16:57 AM Department of Biochemistry, Faculty of Life Sciences, University of Ilorin, Ilorin.
TH E
RO
LES
OF B
IOIN
FOR
MATIC
S IN
THE
DR
UG
DIS
CO
VE
RY
PR
OC
ES
S
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).
![Page 9: The Role of Bioinformatics in The Drug Discovery Process](https://reader036.vdocuments.net/reader036/viewer/2022081521/5877efd91a28ab20088b6f67/html5/thumbnails/9.jpg)
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)
![Page 10: The Role of Bioinformatics in The Drug Discovery Process](https://reader036.vdocuments.net/reader036/viewer/2022081521/5877efd91a28ab20088b6f67/html5/thumbnails/10.jpg)
05/03/2023 10:16:57 AM Department of Biochemistry, Faculty of Life Sciences, University of Ilorin, Ilorin.
TH E
RO
LES
OF B
IOIN
FOR
MATIC
S IN
THE
DR
UG
DIS
CO
VE
RY
PR
OC
ES
S Figure 3 : How expensive the traditional drug discovery is (Jayaram et al.)
![Page 11: The Role of Bioinformatics in The Drug Discovery Process](https://reader036.vdocuments.net/reader036/viewer/2022081521/5877efd91a28ab20088b6f67/html5/thumbnails/11.jpg)
05/03/2023 10:16:57 AM Department of Biochemistry, Faculty of Life Sciences, University of Ilorin, Ilorin.
TH E
RO
LES
OF B
IOIN
FOR
MATIC
S IN
THE
DR
UG
DIS
CO
VE
RY
PR
OC
ES
S
Stages involve in the discovery of drugs (figure 4)
![Page 12: The Role of Bioinformatics in The Drug Discovery Process](https://reader036.vdocuments.net/reader036/viewer/2022081521/5877efd91a28ab20088b6f67/html5/thumbnails/12.jpg)
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
atio
n
Figure 4: Illustrating the stages of drug discovery process (according to Tenthoff, 2006)
![Page 13: The Role of Bioinformatics in The Drug Discovery Process](https://reader036.vdocuments.net/reader036/viewer/2022081521/5877efd91a28ab20088b6f67/html5/thumbnails/13.jpg)
05/03/2023 10:16:57 AM Department of Biochemistry, Faculty of Life Sciences, University of Ilorin, Ilorin.
TH E
RO
LES
OF B
IOIN
FOR
MATIC
S IN
THE
DR
UG
DIS
CO
VE
RY
PR
OC
ES
S
APPLICATION OF BIOINFORMATICS IN
THE DRUG DISCOVERY PROCESS
![Page 14: The Role of Bioinformatics in The Drug Discovery Process](https://reader036.vdocuments.net/reader036/viewer/2022081521/5877efd91a28ab20088b6f67/html5/thumbnails/14.jpg)
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.
TH E
RO
LES
OF B
IOIN
FOR
MATIC
S IN
THE
DR
UG
DIS
CO
VE
RY
PR
OC
ES
S
ROLES OF BIOINFORMATICS IN THE DRUG DISCOVERY PROCESS
![Page 15: The Role of Bioinformatics in The Drug Discovery Process](https://reader036.vdocuments.net/reader036/viewer/2022081521/5877efd91a28ab20088b6f67/html5/thumbnails/15.jpg)
05/03/2023 10:16:57 AM Department of Biochemistry, Faculty of Life Sciences, University of Ilorin, Ilorin.
TH E
RO
LES
OF B
IOIN
FOR
MATIC
S IN
THE
DR
UG
DIS
CO
VE
RY
PR
OC
ES
S
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).
![Page 16: The Role of Bioinformatics in The Drug Discovery Process](https://reader036.vdocuments.net/reader036/viewer/2022081521/5877efd91a28ab20088b6f67/html5/thumbnails/16.jpg)
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).
TH E
RO
LES
OF B
IOIN
FOR
MATIC
S IN
THE
DR
UG
DIS
CO
VE
RY
PR
OC
ES
S
APPLICATIONS OF THE DRUG DISCOVERY PROCESS
![Page 17: The Role of Bioinformatics in The Drug Discovery Process](https://reader036.vdocuments.net/reader036/viewer/2022081521/5877efd91a28ab20088b6f67/html5/thumbnails/17.jpg)
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.
TH E
RO
LES
OF B
IOIN
FOR
MATIC
S IN
THE
DR
UG
DIS
CO
VE
RY
PR
OC
ES
S
![Page 18: The Role of Bioinformatics in The Drug Discovery Process](https://reader036.vdocuments.net/reader036/viewer/2022081521/5877efd91a28ab20088b6f67/html5/thumbnails/18.jpg)
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).
TH E
RO
LES
OF B
IOIN
FOR
MATIC
S IN
THE
DR
UG
DIS
CO
VE
RY
PR
OC
ES
S
![Page 19: The Role of Bioinformatics in The Drug Discovery Process](https://reader036.vdocuments.net/reader036/viewer/2022081521/5877efd91a28ab20088b6f67/html5/thumbnails/19.jpg)
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).
TH E
RO
LES
OF B
IOIN
FOR
MATIC
S IN
THE
DR
UG
DIS
CO
VE
RY
PR
OC
ES
S
![Page 20: The Role of Bioinformatics in The Drug Discovery Process](https://reader036.vdocuments.net/reader036/viewer/2022081521/5877efd91a28ab20088b6f67/html5/thumbnails/20.jpg)
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).
TH E
RO
LES
OF B
IOIN
FOR
MATIC
S IN
THE
DR
UG
DIS
CO
VE
RY
PR
OC
ES
S
![Page 21: The Role of Bioinformatics in The Drug Discovery Process](https://reader036.vdocuments.net/reader036/viewer/2022081521/5877efd91a28ab20088b6f67/html5/thumbnails/21.jpg)
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).
![Page 22: The Role of Bioinformatics in The Drug Discovery Process](https://reader036.vdocuments.net/reader036/viewer/2022081521/5877efd91a28ab20088b6f67/html5/thumbnails/22.jpg)
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.
TH E
RO
LES
OF B
IOIN
FOR
MATIC
S IN
THE
DR
UG
DIS
CO
VE
RY
PR
OC
ES
S
CONCLUSION
![Page 23: The Role of Bioinformatics in The Drug Discovery Process](https://reader036.vdocuments.net/reader036/viewer/2022081521/5877efd91a28ab20088b6f67/html5/thumbnails/23.jpg)
05/03/2023 10:16:58 AM Department of Biochemistry, Faculty of Life Sciences, University of Ilorin, Ilorin.
TH E
RO
LES
OF B
IOIN
FOR
MATIC
S IN
THE
DR
UG
DIS
CO
VE
RY
PR
OC
ES
S
THANK YOU FOR LISTENING
THANK YOU FOR LISTENING
THANK YOU FOR LISTENING
THANK YOU FOR LISTENING