The Experts below are selected from a list of 234 Experts worldwide ranked by ideXlab platform
Per Artursson - One of the best experts on this subject based on the ideXlab platform.
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structural requirements for Drug Inhibition of the liver specific human organic cation transport protein 1
Journal of Medicinal Chemistry, 2008Co-Authors: Gustav Ahlin, Lena Gustavsson, Pär Matsson, Jenny M. Pedersen, Johan Karlsson, Rolf Larsson, Ulf Norinder, Christel A. S. Bergström, Per ArturssonAbstract:The liver-specific organic cation transport protein (OCT1; SLC22A1) transports several cationic Drugs including the antidiabetic Drug metformin and the anticancer agents oxaliplatin and imatinib. I ...
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structural requirements for Drug Inhibition of the liver specific human organic cation transport protein 1
Journal of Medicinal Chemistry, 2008Co-Authors: Gustav Ahlin, Lena Gustavsson, Pär Matsson, Jenny M. Pedersen, Johan Karlsson, Rolf Larsson, Ulf Norinder, Christel A. S. Bergström, Per ArturssonAbstract:The liver-specific organic cation transport protein (OCT1; SLC22A1) transports several cationic Drugs including the antidiabetic Drug metformin and the anticancer agents oxaliplatin and imatinib. In this study, we explored the chemical space of registered oral Drugs with the aim of studying the Inhibition pattern of OCT1 and of developing predictive computational models of OCT1 Inhibition. In total, 191 structurally diverse compounds were examined in HEK293-OCT1 cells. The assay identified 47 novel inhibitors and confirmed 15 previously known inhibitors. The enrichment of OCT1 inhibitors was seen in several Drug classes including antidepressants. High lipophilicity and a positive net charge were found to be the key physicochemical properties for OCT1 Inhibition, whereas a high molecular dipole moment and many hydrogen bonds were negatively correlated to OCT1 Inhibition. The data were used to generate OPLS-DA models for OCT1 inhibitors; the final model correctly predicted 82% of the inhibitors and 88% of the noninhibitors of the test set.
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a global Drug Inhibition pattern for the human atp binding cassette transporter breast cancer resistance protein abcg2
Journal of Pharmacology and Experimental Therapeutics, 2007Co-Authors: Pär Matsson, Gustav Ahlin, Ulf Norinder, Christel A. S. Bergström, Gunilla Englund, Per ArturssonAbstract:In this article, we explore the entire structural space of registered Drugs to obtain a global model for the Inhibition of the Drug efflux transporter breast cancer resistance protein (BCRP; ABCG2). For this purpose, the inhibitory effect of 123 structurally diverse Drugs and Drug-like compounds on mitoxantrone efflux was studied in Saos-2 cells transfected with human wild-type (Arg482) BCRP. The search for BCRP inhibitors throughout the Drug-like chemical space resulted in the identification of 29 previously unknown inhibitors. The frequency of BCRP Inhibition was 3 times higher for compounds reported to interact with other ATP-binding cassette (ABC) transporters than for compounds without reported ABC transporter affinity. An easily interpreted computational model capable of discriminating inhibitors from noninhibitors using only two molecular descriptors, octanol-water partition coefficient at pH 7.4 and molecular polarizability, was constructed. The discriminating power of this two-descriptor model was 93% for the training set and 79% for the test set, respectively. The results were supported by a global pharmacophore model and are in agreement with a two-step mechanism for the Inhibition of BCRP, where both the Drug's capacity to insert into the cell membrane and to interact with the inhibitory binding site of the transporter are important.
Gustav Ahlin - One of the best experts on this subject based on the ideXlab platform.
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structural requirements for Drug Inhibition of the liver specific human organic cation transport protein 1
Journal of Medicinal Chemistry, 2008Co-Authors: Gustav Ahlin, Lena Gustavsson, Pär Matsson, Jenny M. Pedersen, Johan Karlsson, Rolf Larsson, Ulf Norinder, Christel A. S. Bergström, Per ArturssonAbstract:The liver-specific organic cation transport protein (OCT1; SLC22A1) transports several cationic Drugs including the antidiabetic Drug metformin and the anticancer agents oxaliplatin and imatinib. I ...
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structural requirements for Drug Inhibition of the liver specific human organic cation transport protein 1
Journal of Medicinal Chemistry, 2008Co-Authors: Gustav Ahlin, Lena Gustavsson, Pär Matsson, Jenny M. Pedersen, Johan Karlsson, Rolf Larsson, Ulf Norinder, Christel A. S. Bergström, Per ArturssonAbstract:The liver-specific organic cation transport protein (OCT1; SLC22A1) transports several cationic Drugs including the antidiabetic Drug metformin and the anticancer agents oxaliplatin and imatinib. In this study, we explored the chemical space of registered oral Drugs with the aim of studying the Inhibition pattern of OCT1 and of developing predictive computational models of OCT1 Inhibition. In total, 191 structurally diverse compounds were examined in HEK293-OCT1 cells. The assay identified 47 novel inhibitors and confirmed 15 previously known inhibitors. The enrichment of OCT1 inhibitors was seen in several Drug classes including antidepressants. High lipophilicity and a positive net charge were found to be the key physicochemical properties for OCT1 Inhibition, whereas a high molecular dipole moment and many hydrogen bonds were negatively correlated to OCT1 Inhibition. The data were used to generate OPLS-DA models for OCT1 inhibitors; the final model correctly predicted 82% of the inhibitors and 88% of the noninhibitors of the test set.
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a global Drug Inhibition pattern for the human atp binding cassette transporter breast cancer resistance protein abcg2
Journal of Pharmacology and Experimental Therapeutics, 2007Co-Authors: Pär Matsson, Gustav Ahlin, Ulf Norinder, Christel A. S. Bergström, Gunilla Englund, Per ArturssonAbstract:In this article, we explore the entire structural space of registered Drugs to obtain a global model for the Inhibition of the Drug efflux transporter breast cancer resistance protein (BCRP; ABCG2). For this purpose, the inhibitory effect of 123 structurally diverse Drugs and Drug-like compounds on mitoxantrone efflux was studied in Saos-2 cells transfected with human wild-type (Arg482) BCRP. The search for BCRP inhibitors throughout the Drug-like chemical space resulted in the identification of 29 previously unknown inhibitors. The frequency of BCRP Inhibition was 3 times higher for compounds reported to interact with other ATP-binding cassette (ABC) transporters than for compounds without reported ABC transporter affinity. An easily interpreted computational model capable of discriminating inhibitors from noninhibitors using only two molecular descriptors, octanol-water partition coefficient at pH 7.4 and molecular polarizability, was constructed. The discriminating power of this two-descriptor model was 93% for the training set and 79% for the test set, respectively. The results were supported by a global pharmacophore model and are in agreement with a two-step mechanism for the Inhibition of BCRP, where both the Drug's capacity to insert into the cell membrane and to interact with the inhibitory binding site of the transporter are important.
Pär Matsson - One of the best experts on this subject based on the ideXlab platform.
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structural requirements for Drug Inhibition of the liver specific human organic cation transport protein 1
Journal of Medicinal Chemistry, 2008Co-Authors: Gustav Ahlin, Lena Gustavsson, Pär Matsson, Jenny M. Pedersen, Johan Karlsson, Rolf Larsson, Ulf Norinder, Christel A. S. Bergström, Per ArturssonAbstract:The liver-specific organic cation transport protein (OCT1; SLC22A1) transports several cationic Drugs including the antidiabetic Drug metformin and the anticancer agents oxaliplatin and imatinib. I ...
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structural requirements for Drug Inhibition of the liver specific human organic cation transport protein 1
Journal of Medicinal Chemistry, 2008Co-Authors: Gustav Ahlin, Lena Gustavsson, Pär Matsson, Jenny M. Pedersen, Johan Karlsson, Rolf Larsson, Ulf Norinder, Christel A. S. Bergström, Per ArturssonAbstract:The liver-specific organic cation transport protein (OCT1; SLC22A1) transports several cationic Drugs including the antidiabetic Drug metformin and the anticancer agents oxaliplatin and imatinib. In this study, we explored the chemical space of registered oral Drugs with the aim of studying the Inhibition pattern of OCT1 and of developing predictive computational models of OCT1 Inhibition. In total, 191 structurally diverse compounds were examined in HEK293-OCT1 cells. The assay identified 47 novel inhibitors and confirmed 15 previously known inhibitors. The enrichment of OCT1 inhibitors was seen in several Drug classes including antidepressants. High lipophilicity and a positive net charge were found to be the key physicochemical properties for OCT1 Inhibition, whereas a high molecular dipole moment and many hydrogen bonds were negatively correlated to OCT1 Inhibition. The data were used to generate OPLS-DA models for OCT1 inhibitors; the final model correctly predicted 82% of the inhibitors and 88% of the noninhibitors of the test set.
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a global Drug Inhibition pattern for the human atp binding cassette transporter breast cancer resistance protein abcg2
Journal of Pharmacology and Experimental Therapeutics, 2007Co-Authors: Pär Matsson, Gustav Ahlin, Ulf Norinder, Christel A. S. Bergström, Gunilla Englund, Per ArturssonAbstract:In this article, we explore the entire structural space of registered Drugs to obtain a global model for the Inhibition of the Drug efflux transporter breast cancer resistance protein (BCRP; ABCG2). For this purpose, the inhibitory effect of 123 structurally diverse Drugs and Drug-like compounds on mitoxantrone efflux was studied in Saos-2 cells transfected with human wild-type (Arg482) BCRP. The search for BCRP inhibitors throughout the Drug-like chemical space resulted in the identification of 29 previously unknown inhibitors. The frequency of BCRP Inhibition was 3 times higher for compounds reported to interact with other ATP-binding cassette (ABC) transporters than for compounds without reported ABC transporter affinity. An easily interpreted computational model capable of discriminating inhibitors from noninhibitors using only two molecular descriptors, octanol-water partition coefficient at pH 7.4 and molecular polarizability, was constructed. The discriminating power of this two-descriptor model was 93% for the training set and 79% for the test set, respectively. The results were supported by a global pharmacophore model and are in agreement with a two-step mechanism for the Inhibition of BCRP, where both the Drug's capacity to insert into the cell membrane and to interact with the inhibitory binding site of the transporter are important.
Christel A. S. Bergström - One of the best experts on this subject based on the ideXlab platform.
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structural requirements for Drug Inhibition of the liver specific human organic cation transport protein 1
Journal of Medicinal Chemistry, 2008Co-Authors: Gustav Ahlin, Lena Gustavsson, Pär Matsson, Jenny M. Pedersen, Johan Karlsson, Rolf Larsson, Ulf Norinder, Christel A. S. Bergström, Per ArturssonAbstract:The liver-specific organic cation transport protein (OCT1; SLC22A1) transports several cationic Drugs including the antidiabetic Drug metformin and the anticancer agents oxaliplatin and imatinib. I ...
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structural requirements for Drug Inhibition of the liver specific human organic cation transport protein 1
Journal of Medicinal Chemistry, 2008Co-Authors: Gustav Ahlin, Lena Gustavsson, Pär Matsson, Jenny M. Pedersen, Johan Karlsson, Rolf Larsson, Ulf Norinder, Christel A. S. Bergström, Per ArturssonAbstract:The liver-specific organic cation transport protein (OCT1; SLC22A1) transports several cationic Drugs including the antidiabetic Drug metformin and the anticancer agents oxaliplatin and imatinib. In this study, we explored the chemical space of registered oral Drugs with the aim of studying the Inhibition pattern of OCT1 and of developing predictive computational models of OCT1 Inhibition. In total, 191 structurally diverse compounds were examined in HEK293-OCT1 cells. The assay identified 47 novel inhibitors and confirmed 15 previously known inhibitors. The enrichment of OCT1 inhibitors was seen in several Drug classes including antidepressants. High lipophilicity and a positive net charge were found to be the key physicochemical properties for OCT1 Inhibition, whereas a high molecular dipole moment and many hydrogen bonds were negatively correlated to OCT1 Inhibition. The data were used to generate OPLS-DA models for OCT1 inhibitors; the final model correctly predicted 82% of the inhibitors and 88% of the noninhibitors of the test set.
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a global Drug Inhibition pattern for the human atp binding cassette transporter breast cancer resistance protein abcg2
Journal of Pharmacology and Experimental Therapeutics, 2007Co-Authors: Pär Matsson, Gustav Ahlin, Ulf Norinder, Christel A. S. Bergström, Gunilla Englund, Per ArturssonAbstract:In this article, we explore the entire structural space of registered Drugs to obtain a global model for the Inhibition of the Drug efflux transporter breast cancer resistance protein (BCRP; ABCG2). For this purpose, the inhibitory effect of 123 structurally diverse Drugs and Drug-like compounds on mitoxantrone efflux was studied in Saos-2 cells transfected with human wild-type (Arg482) BCRP. The search for BCRP inhibitors throughout the Drug-like chemical space resulted in the identification of 29 previously unknown inhibitors. The frequency of BCRP Inhibition was 3 times higher for compounds reported to interact with other ATP-binding cassette (ABC) transporters than for compounds without reported ABC transporter affinity. An easily interpreted computational model capable of discriminating inhibitors from noninhibitors using only two molecular descriptors, octanol-water partition coefficient at pH 7.4 and molecular polarizability, was constructed. The discriminating power of this two-descriptor model was 93% for the training set and 79% for the test set, respectively. The results were supported by a global pharmacophore model and are in agreement with a two-step mechanism for the Inhibition of BCRP, where both the Drug's capacity to insert into the cell membrane and to interact with the inhibitory binding site of the transporter are important.
Ulf Norinder - One of the best experts on this subject based on the ideXlab platform.
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structural requirements for Drug Inhibition of the liver specific human organic cation transport protein 1
Journal of Medicinal Chemistry, 2008Co-Authors: Gustav Ahlin, Lena Gustavsson, Pär Matsson, Jenny M. Pedersen, Johan Karlsson, Rolf Larsson, Ulf Norinder, Christel A. S. Bergström, Per ArturssonAbstract:The liver-specific organic cation transport protein (OCT1; SLC22A1) transports several cationic Drugs including the antidiabetic Drug metformin and the anticancer agents oxaliplatin and imatinib. I ...
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structural requirements for Drug Inhibition of the liver specific human organic cation transport protein 1
Journal of Medicinal Chemistry, 2008Co-Authors: Gustav Ahlin, Lena Gustavsson, Pär Matsson, Jenny M. Pedersen, Johan Karlsson, Rolf Larsson, Ulf Norinder, Christel A. S. Bergström, Per ArturssonAbstract:The liver-specific organic cation transport protein (OCT1; SLC22A1) transports several cationic Drugs including the antidiabetic Drug metformin and the anticancer agents oxaliplatin and imatinib. In this study, we explored the chemical space of registered oral Drugs with the aim of studying the Inhibition pattern of OCT1 and of developing predictive computational models of OCT1 Inhibition. In total, 191 structurally diverse compounds were examined in HEK293-OCT1 cells. The assay identified 47 novel inhibitors and confirmed 15 previously known inhibitors. The enrichment of OCT1 inhibitors was seen in several Drug classes including antidepressants. High lipophilicity and a positive net charge were found to be the key physicochemical properties for OCT1 Inhibition, whereas a high molecular dipole moment and many hydrogen bonds were negatively correlated to OCT1 Inhibition. The data were used to generate OPLS-DA models for OCT1 inhibitors; the final model correctly predicted 82% of the inhibitors and 88% of the noninhibitors of the test set.
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a global Drug Inhibition pattern for the human atp binding cassette transporter breast cancer resistance protein abcg2
Journal of Pharmacology and Experimental Therapeutics, 2007Co-Authors: Pär Matsson, Gustav Ahlin, Ulf Norinder, Christel A. S. Bergström, Gunilla Englund, Per ArturssonAbstract:In this article, we explore the entire structural space of registered Drugs to obtain a global model for the Inhibition of the Drug efflux transporter breast cancer resistance protein (BCRP; ABCG2). For this purpose, the inhibitory effect of 123 structurally diverse Drugs and Drug-like compounds on mitoxantrone efflux was studied in Saos-2 cells transfected with human wild-type (Arg482) BCRP. The search for BCRP inhibitors throughout the Drug-like chemical space resulted in the identification of 29 previously unknown inhibitors. The frequency of BCRP Inhibition was 3 times higher for compounds reported to interact with other ATP-binding cassette (ABC) transporters than for compounds without reported ABC transporter affinity. An easily interpreted computational model capable of discriminating inhibitors from noninhibitors using only two molecular descriptors, octanol-water partition coefficient at pH 7.4 and molecular polarizability, was constructed. The discriminating power of this two-descriptor model was 93% for the training set and 79% for the test set, respectively. The results were supported by a global pharmacophore model and are in agreement with a two-step mechanism for the Inhibition of BCRP, where both the Drug's capacity to insert into the cell membrane and to interact with the inhibitory binding site of the transporter are important.
