Mgr. Peter Š ramel, Katedra organickej chémie, PriF UK
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Transcript of Mgr. Peter Š ramel, Katedra organickej chémie, PriF UK
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Objav Mer-špecifického tyrozín kinázového inhibítora a jeho
aplikácia pri liečbe a prevencii trombózy
Mgr. Peter Šramel, Katedra organickej chémie, PriF UK
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Krvné doštičky (trombocity, platelety)
www. medimoon.com
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Funkcia krvných doštičiek
www.atvb.ahajournals.com
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Trombóza
www.ortho.com
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1. vs 2. generácia MER inhibítorov
Zhang, W. et al. J. Med. Chem. September 9, 2013.
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Syntéza základného (pyrimidínového) skeletu
Zhang, W. et al. J. Med. Chem. September 9, 2013.
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SAR (kľúčové pozorovanie)
Zhang, W. et al. J. Med. Chem. September 9, 2013.
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SAR (R1 poloha)
Zhang, W. et al. J. Med. Chem. September 9, 2013.
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SAR (R2 poloha)
Zhang, W. et al. J. Med. Chem. September 9, 2013.
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SAR (R3 poloha)
Zhang, W. et al. J. Med. Chem. September 9, 2013.
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Analýza väzbových interakcií
N
NNH
NH
NH
O
HO
SNH2
O O
22IC50 Mer 5.2 nM
Axl 260 nMTyro3 280 nM
N
NNH
NH
N
O
HO
7IC50 Mer 5900 nMAxl >30 000 nM
Tyro3 >30 000 nM
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Finálna „lead compound“
N
NNH
NH
NH
O
HO
23 (UNC2881)IC50 Mer 4.3 nM
Axl 360 nMTyro3 250 nM
N
N
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ĎAKUJEM VÁM ZA POZORNOSŤ
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ATP