A brief bioinformatics approach to design matrix metallo proteinase inhibitors.

1. A New Approach to Design
Matrix metalloprotienase Inhibitors
Venu Thatikonda
M.S(pharm)- PI-15

2. Introduction of MMP
 Role in cancer
 MMP-inhibitors
 Computer Aided Drug Design
 Virtual screening
 Docking
Contents

3. MMP’s
 Matrix metalloprotienases are Zn-dependent
endopeptidases.
 Catalytic domain contains 2 ‘Zn’ atoms.
 Degrades all kinds of extracellular matrix proteins.

4. MMP’s
Role in CANCER :
 Increased IGF by cleaving IGF-BP
 Cleavage of FAS ligand
 Regulate ‘Invasion & Metastasis’

5. MMP’s
 Promote Angiogenesis by increasing the
levels of
 VEGF
 FGF-2
 TGF

6. MMP-Inhibitors
 Drugs which inhibit the activities of these
MMP’s are helpful in the treatment of cancer
Eg – Batimastat (BB-94)
 A new approach to design these drugs is
“Computer Based Drug Designing”

7. Determination of Crystal structure of Target
Drawing 2D structure
Converting it to 3D using computers
The concept of CBDD includes..

8. Continues..
‘Virtual screening’ of Chemical libraries(Ligands)
‘Docking’ of ligand & Target
Hit compound evaluation
In-vivo experiments

10.  Virtual screening :
Automatically evaluating very large libraries
of compounds using computer programs.
- Ligand based
- Structure based

11. Virtual screening

12.  Docking :
It is a method which predicts the preferred
orientation of one molecule to a second when
bound to each other to form a stable complex.

13. Docking

14. After Docking evaluation is done for the size, chemical,
Physilogical properties through 3D QSAR
Hit compound evaluation in-vivo

15. Refference :
 Rollinger JM, Stuppner H, Langer T (2008). "Virtual screening for the
discovery of bioactive natural products". Prog Drug Res. Progress in
Drug Research 65 (211): 213–49.
 "Pharmacophore-based virtual screening".
Curr Med Chem 15 (10): 1018–24.
 "Computational methods for biomolecular docking".
Curr. Opin. Struct. Biol. 6 (3): 402–6.

16. Any Questions ??

17. Do Work to Empty your BRAIN &
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