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niTza Biologicals April,2007
Enriching Bio-Science .
niTza Biologicals April,2007
Enriching Bio-Science .
niTza Biologicals April,2007
Enriching Bio-Science .
niTza Biologicals April,2007
Enriching Bio-Science .
niTza Biologicals April,2007
Enriching Bio-Science .
niTza Biologicals April,2007
Enriching Bio-Science .
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PRINCIPLES OF DRUG DESIGNING
DRUG DISCOVERY PROCESS
1) Target Identification.
2) Target Validation.3) Lead Identification.
4) Lead Optimization.
5) Preclinical Pharmacology & Toxicology
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WHAT ISADRUG ?
Drug is a molecule that designed to bind, interact or
to modulate the action of specific biological receptor;
The Biological Receptor may be a cell surface receptor
(Hormone receptor, Neurotransmitter receptor) or may
be any enzyme whose activity has been altered by any
physiological stresses or due to genetic abnormalities, etc.
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PROPERTIES OFAN IDEAL LIGAND
Steric complementarity
Physico-chemical complementarity
Electrostatic complementarity
Hydrophobic interactions
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MAINAPPROACHES OF DRUG DESIGNING
1) Ligand basedApproaches :-(a) Ligand Unknown :-
- Combinatorial Chemistry used to generate a large
libraries of molecules which can be screened for
biologically active compound.
(b) Ligand Known :-
- a set of active ligand molecules is known for themacromolecular target but a little information
exist for the target.
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Ligand Known :-
1) QSARMethod :-
It involves the statistical analysis of a set of properties or
descriptor for a series of biologically active molecules.
The Statistical model developed then is used to predict
the activity of additional compounds against the target.
eg., Mol. Wt., Volume, Solvent Accessible Surface Area,
Mol. Interaction field.
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2) PharmacophoreModel :-
Depending upon the size of the active site there
may be numerous Steric, electrostatic & hydrophobic
interactions.
The specific interactions that are crucial for the ligand
recognition and binding by the receptor are termed asPharmacophore.
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2)Target basedApproach :-
(a) Ligand known :-
- Docking :- It involves scanning a database of knownmolecules for those likely to bind well to the receptor.
It generate possible binding geometry for each
molecule and evaluate the score for each.
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(b) Ligand Unknown :-
- De novo designing :-
Used to build a customized ligand for a given receptor.
Identify favourable interaction points on receptor.
Choose complementary groups.
Connect them into a molecular frame work.
- Receptor based 3D searching
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Protein-Drug Interaction
Mechanism of
Drug Action:
A drug interferes withthe function of a
disease protein bybinding to it.
This interferencestops the diseaseprocess
Drug Design:
Structure of diseaseprotein is very useful
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Protein-Drug Interaction
Mechanism of
Drug Action:
A drug interferes withthe function of a
disease protein bybinding to it.
This interferencestops the diseaseprocess
Drug Design:
Structure of diseaseprotein is very useful
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DRUG DESIGNING SOFTWARES
AutoDock
Dock
LUDI LEGEND
Hook
HYPERCHEM
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Drug Design CycleDrug Design Cycle
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TH NK YOUTH NK YOU
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