1A2 | Two positive potentials and two negative potentials are required for quinolone inhibitors. |
Fuhr et al., 1993
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| Planar molecules with a small volume to surface area are potent inhibitors. |
Lee et al., 1998
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| Identified positions of hydrogen bonding and hydrophobic groups for inhibitors |
Lozano et al., 2000
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2A6 | Potent CYP2A6 inhibitors do not include a lactone constituent. |
Poso et al., 2001
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2B6 | Substrates possess at least three hydrophobes and one hydrogen bond acceptor. |
Ekins et al., 1999c
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2C9 | Hydrogen bond donor 7 Å from site of metabolism in substrates |
Jones et al., 1996a
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| The distance between the hydroxylation site and the anionic site is 7.8 Å. There is a hydrophobic zone between the hydroxylation site and the cationic site on the protein. |
Mancy et al., 1995 Mancy et al., 1996
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| Inhibitors display two cationic enzyme binding sites that were predicted to be important, along with the aromatic binding region, and a steric region. Favorable interactions occur when the substrate has a partial negative charge 10 Å from the oxidation site, with a second position of favored negative charge on the substrate 6 Å from the oxidation site and 35 degrees clockwise from the first electrostatic site. |
Jones et al., 1996b Rao et al., 2000
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| Inhibitor models had at least one hydrophobic region and one hydrogen bond acceptor. The hydrogen bond acceptor and the hydrogen bond donor/acceptor are 3.4 to 5.7 Å apart, with the hydrophobic region 3 to 5.8 Å from the hydrogen bond acceptor. |
Ekins et al., 2000a
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2D6 | Substrates possess a basic nitrogen atom at either 5 or 7 Å from the site of oxidation, and aromatic rings that are coplanar. |
Wolff et al., 1985; Meyer et al., 1986 Islam et al., 1991
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| Substrates possess a carboxylate group within the protein responsible for a well defined distance of either 5 or 7 Å between basic nitrogen atom and the site of oxidation within the substrate. |
Koymans et al., 1992
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| An aspartic acid residue was coupled to the basic nitrogen atoms. |
de Groot et al., 1997a
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| Two substrate pharmacophores (one forO-dealkylation and oxidation reactions and a second one forN-dealkylation reactions catalyzed by CYP2D6) were generated. |
de Groot et al., 1999a,b |
| Inhibitor model contains a tertiary nitrogen atom (protonated at physiological pH) and a flat hydrophobic region plus two regions in which functional groups with lone pairs are allowed. |
Strobl et al., 1993
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| Inhibitor pharmacophores contain a hydrogen bond acceptor and a hydrogen bond donor and two to three hydrophobic regions. |
Ekins et al., 1999a
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2E1 | Long hydrophobic access channel |
Waller et al., 1996
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3A4 | Substrate model includes hydrogen bond acceptor atom 5.5 to 7.8 Å from the site of metabolism and 3 Å from the oxygen molecule associated with the heme. |
Lewis et al., 1996
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| Inhibitor pharmacophores include three hydrophobes at distances of 5.2 to 8.8 Å from a hydrogen bond acceptor, three hydrophobes at distances of 4.2 to 7.1 Å from a hydrogen bond acceptor and an additional 5.2 Å from another hydrogen bond acceptor, or one hydrophobe at distances from 8.1 to 16.3 Å from the two furthest of three hydrogen bond acceptors |
Ekins et al., 1999b
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| Substrate pharmacophore possessed two hydrogen bond acceptors, one hydrogen bond donor, and one hydrophobic region. |
Ekins et al., 1999d
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