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Acetanilide, Acetylsalicylic acid, Amphetamine, Chloral hydrate, Cisplatin, Clonidine,
Cromoglycate, Cyclosporin, Dicoumarol, Diethylstilbestrol, Haloperidol, Heparin, Imipramine,
Iproniazid, Isoniazid, Levamisole, Lithium carbonate, Lysergide (LSD), Nitroglycerine,
Penicilli, Sulfonamides, Tamoxifen,Urethane, Valproic acid, Warfarin.

 2000 -


, ,
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screening (HTS)
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Screen smarter, not faster.

,
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9

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Log (1/C)-
C-

12

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13

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14

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Log biologic response versus log partition coefficient usina linear. oarabolic. and
bilinear models.

-
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15

- .

R=NO2
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16

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17

 .
.

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18

 -
(
leading compound) (
).
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100 000 database
.
virtual screening (
) :
-

2D

- pharmacophore

3D : molecular docking.

2D .

, HTS drug like
.
,
.
3D
.

.
virtual screening.
19


,
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logP) (
).
database.
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drug-like
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20

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hits. hits,
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2D 3D


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21


.
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PDB
(protein data bank) .

PDB file ATPO GluR2

PDB 3D
docking

pKa
His:

C,O N
: his, thr, asn, gln

22

K :

, . 15 .
2D 3D
.
docking:

-

pH

( , log P,
, , )

non-drug :
<200 >600, logP>7,
>8 >8.

2D

3D :
-

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.

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. box grid
10
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23

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grid . van der Waals
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24

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GluR2-ATPO ()

ATPO-GluR2
3D

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25

Phenylalanine-ATPO
GluR -

ATPO 100
4,5 6.
. GluR2
EL-7.
EL-7
HOOC

COOH

H2N

Cl

NO2

EL-7 GluR2
ATPO

.
.
26


ATP.

.

2,52 .
docking, EL-7
.

EL-7
GluR2

EL-7 GluR2


X-ray.
EL-7 GluR2 :

1)

2)

27


:
-
.

docking :
hits
? HTS ,

.
docking (1-10% )
hits . virtual screening
HTS,
. (
drug-like

).

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vacuo)
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+
+ , ,
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3D QSAR-
HTS

.

28

600-1500
.
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(GPCRs,
, , , , .)
: (
)
: ,
().

29

 : GPCRs, , ,, ,
/ , , .
90%
9 22 22-
bcr-abl .
.

STI 571 (Imatinib, Glivec, Novartis)

PKC-protein kinase C
Imatinib

30