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David H Munn - One of the best experts on this subject based on the ideXlab platform.
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inhibition of inDoleamine 2 3 Dioxygenase in DenDritic cells by stereoIsomers of 1 methyl tryptophan correlates with antitumor responses
Cancer Research, 2007Co-Authors: De Yan Hou, Alexander J Muller, Madhav D Sharma, James B Duhadaway, Tinku Banerjee, Maribeth H Johnson, Andrew L Mellor, George C Prendergast, David H MunnAbstract:InDoleamine 2,3-Dioxygenase (IDO) is an immunosuppressive enzyme that contributes to tolerance in a number of biological settings. In cancer, IDO activity may help promote acquireD tolerance to tumor antigens. The IDO inhibitor 1-methyl-tryptophan is being DevelopeD for clinical trials. However, 1-methyl-tryptophan exists in two stereoIsomers with potentially Different biological properties, anD it has been unclear which Isomer might be preferable for initial Development. In this stuDy, we proviDe eviDence that the D anD L stereoIsomers exhibit important cell type-specific variations in activity. The L Isomer was the more potent inhibitor of IDO activity using the purifieD enzyme anD in HeLa cell-baseD assays. However, the D Isomer was significantly more effective in reversing the suppression of T cells createD by IDO-expressing DenDritic cells, using both human monocyte-DeriveD DenDritic cells anD murine DenDritic cells isolateD Directly from tumor-Draining lymph noDes. In vivo, the D Isomer was more efficacious as an anticancer agent in chemo-immunotherapy regimens using cyclophosphamiDe, paclitaxel, or gemcitabine, when testeD in mouse moDels of transplantable melanoma anD transplantable anD autochthonous breast cancer. The D Isomer of 1-methyl-tryptophan specifically targeteD the IDO gene because the antitumor effect of D-1-methyl-tryptophan was completely lost in mice with a Disruption of the IDO gene (IDO-knockout mice). Taken together, our finDings support the suitability of D-1-methyl-tryptophan for human trials aiming to assess the utility of IDO inhibition to block host-meDiateD immunosuppression anD enhance antitumor immunity in the setting of combineD chemo-immunotherapy regimens.
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inhibition of inDoleamine 2 3 Dioxygenase in DenDritic cells by stereoIsomers of 1 methyl tryptophan correlates with antitumor responses
Cancer Research, 2007Co-Authors: Alexander J Muller, Madhav D Sharma, James B Duhadaway, Tinku Banerjee, Maribeth H Johnson, Andrew L Mellor, George C Prendergast, David H MunnAbstract:InDoleamine 2,3-Dioxygenase (IDO) is an immunosuppressive enzyme that contributes to tolerance in a number of biological settings. In cancer, IDO activity may help promote acquireD tolerance to tumor antigens. The IDO inhibitor 1-methyl-tryptophan is being DevelopeD for clinical trials. However, 1-methyl-tryptophan exists in two stereoIsomers with potentially Different biological properties, anD it has been unclear which Isomer might be preferable for initial Development. In this stuDy, we proviDe eviDence that the D anD l stereoIsomers exhibit important cell type–specific variations in activity. The l Isomer was the more potent inhibitor of IDO activity using the purifieD enzyme anD in HeLa cell–baseD assays. However, the D Isomer was significantly more effective in reversing the suppression of T cells createD by IDO-expressing DenDritic cells, using both human monocyte–DeriveD DenDritic cells anD murine DenDritic cells isolateD Directly from tumor-Draining lymph noDes. In vivo , the D Isomer was more efficacious as an anticancer agent in chemo-immunotherapy regimens using cyclophosphamiDe, paclitaxel, or gemcitabine, when testeD in mouse moDels of transplantable melanoma anD transplantable anD autochthonous breast cancer. The D Isomer of 1-methyl-tryptophan specifically targeteD the IDO gene because the antitumor effect of D-1-methyl-tryptophan was completely lost in mice with a Disruption of the IDO gene (IDO-knockout mice). Taken together, our finDings support the suitability of D-1-methyl-tryptophan for human trials aiming to assess the utility of IDO inhibition to block host-meDiateD immunosuppression anD enhance antitumor immunity in the setting of combineD chemo-immunotherapy regimens. [Cancer Res 2007;67(2):792–801]
Carrie Haskellluevano - One of the best experts on this subject based on the ideXlab platform.
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arg phe phe D amino aciD stereochemistry scan in the macrocyclic agouti relateD protein antagonist scaffolD c pro arg phe phe xxx ala phe Dpro results in unanticipateD melanocortin 1 receptor agonist profiles
ACS Chemical Neuroscience, 2018Co-Authors: Mark D Ericson, Katie T Freeman, Katlyn A Fleming, Zoe M Koerperich, Carrie HaskellluevanoAbstract:The melanocortin-3 anD melanocortin-4 receptors (MC3R anD MC4R), enDogenous agonists DeriveD from the proopiomelanocortin gene transcript, anD naturally occurring antagonists agouti anD agouti-relateD protein (AGRP) have been linkeD to biological pathways associateD with energy homeostasis. The active tripeptiDe sequence of AGRP, Arg111-Phe112-Phe113, is locateD on a hypothesizeD β-hairpin loop. Herein, stereochemical moDifications of the Arg-Phe-Phe sequence were examineD in the octapeptiDe AGRP-DeriveD macrocyclic scaffolD c[Pro-Arg-Phe-Phe-Xxx-Ala-Phe-DPro], where Xxx was Asn or Diaminopropionic aciD (Dap). Macrocyclic peptiDes were synthesizeD with one, two, or three resiDues of the Arg-Phe-Phe sequence substituteD with the corresponDing D-Isomer(s), generating a 14 compounD library. While l-to-D inversions of the Arg-Phe-Phe sequence in a 20-resiDue AGRP-DeriveD liganD previously resulteD in agonist activity at the MC1R, MC3R, MC4R, anD MC5R, only the MC1R was consistently stimulateD by the macrocycl...
Alexander J Muller - One of the best experts on this subject based on the ideXlab platform.
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inhibition of inDoleamine 2 3 Dioxygenase in DenDritic cells by stereoIsomers of 1 methyl tryptophan correlates with antitumor responses
Cancer Research, 2007Co-Authors: De Yan Hou, Alexander J Muller, Madhav D Sharma, James B Duhadaway, Tinku Banerjee, Maribeth H Johnson, Andrew L Mellor, George C Prendergast, David H MunnAbstract:InDoleamine 2,3-Dioxygenase (IDO) is an immunosuppressive enzyme that contributes to tolerance in a number of biological settings. In cancer, IDO activity may help promote acquireD tolerance to tumor antigens. The IDO inhibitor 1-methyl-tryptophan is being DevelopeD for clinical trials. However, 1-methyl-tryptophan exists in two stereoIsomers with potentially Different biological properties, anD it has been unclear which Isomer might be preferable for initial Development. In this stuDy, we proviDe eviDence that the D anD L stereoIsomers exhibit important cell type-specific variations in activity. The L Isomer was the more potent inhibitor of IDO activity using the purifieD enzyme anD in HeLa cell-baseD assays. However, the D Isomer was significantly more effective in reversing the suppression of T cells createD by IDO-expressing DenDritic cells, using both human monocyte-DeriveD DenDritic cells anD murine DenDritic cells isolateD Directly from tumor-Draining lymph noDes. In vivo, the D Isomer was more efficacious as an anticancer agent in chemo-immunotherapy regimens using cyclophosphamiDe, paclitaxel, or gemcitabine, when testeD in mouse moDels of transplantable melanoma anD transplantable anD autochthonous breast cancer. The D Isomer of 1-methyl-tryptophan specifically targeteD the IDO gene because the antitumor effect of D-1-methyl-tryptophan was completely lost in mice with a Disruption of the IDO gene (IDO-knockout mice). Taken together, our finDings support the suitability of D-1-methyl-tryptophan for human trials aiming to assess the utility of IDO inhibition to block host-meDiateD immunosuppression anD enhance antitumor immunity in the setting of combineD chemo-immunotherapy regimens.
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inhibition of inDoleamine 2 3 Dioxygenase in DenDritic cells by stereoIsomers of 1 methyl tryptophan correlates with antitumor responses
Cancer Research, 2007Co-Authors: Alexander J Muller, Madhav D Sharma, James B Duhadaway, Tinku Banerjee, Maribeth H Johnson, Andrew L Mellor, George C Prendergast, David H MunnAbstract:InDoleamine 2,3-Dioxygenase (IDO) is an immunosuppressive enzyme that contributes to tolerance in a number of biological settings. In cancer, IDO activity may help promote acquireD tolerance to tumor antigens. The IDO inhibitor 1-methyl-tryptophan is being DevelopeD for clinical trials. However, 1-methyl-tryptophan exists in two stereoIsomers with potentially Different biological properties, anD it has been unclear which Isomer might be preferable for initial Development. In this stuDy, we proviDe eviDence that the D anD l stereoIsomers exhibit important cell type–specific variations in activity. The l Isomer was the more potent inhibitor of IDO activity using the purifieD enzyme anD in HeLa cell–baseD assays. However, the D Isomer was significantly more effective in reversing the suppression of T cells createD by IDO-expressing DenDritic cells, using both human monocyte–DeriveD DenDritic cells anD murine DenDritic cells isolateD Directly from tumor-Draining lymph noDes. In vivo , the D Isomer was more efficacious as an anticancer agent in chemo-immunotherapy regimens using cyclophosphamiDe, paclitaxel, or gemcitabine, when testeD in mouse moDels of transplantable melanoma anD transplantable anD autochthonous breast cancer. The D Isomer of 1-methyl-tryptophan specifically targeteD the IDO gene because the antitumor effect of D-1-methyl-tryptophan was completely lost in mice with a Disruption of the IDO gene (IDO-knockout mice). Taken together, our finDings support the suitability of D-1-methyl-tryptophan for human trials aiming to assess the utility of IDO inhibition to block host-meDiateD immunosuppression anD enhance antitumor immunity in the setting of combineD chemo-immunotherapy regimens. [Cancer Res 2007;67(2):792–801]
Mark D Ericson - One of the best experts on this subject based on the ideXlab platform.
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arg phe phe D amino aciD stereochemistry scan in the macrocyclic agouti relateD protein antagonist scaffolD c pro arg phe phe xxx ala phe Dpro results in unanticipateD melanocortin 1 receptor agonist profiles
ACS Chemical Neuroscience, 2018Co-Authors: Mark D Ericson, Katie T Freeman, Katlyn A Fleming, Zoe M Koerperich, Carrie HaskellluevanoAbstract:The melanocortin-3 anD melanocortin-4 receptors (MC3R anD MC4R), enDogenous agonists DeriveD from the proopiomelanocortin gene transcript, anD naturally occurring antagonists agouti anD agouti-relateD protein (AGRP) have been linkeD to biological pathways associateD with energy homeostasis. The active tripeptiDe sequence of AGRP, Arg111-Phe112-Phe113, is locateD on a hypothesizeD β-hairpin loop. Herein, stereochemical moDifications of the Arg-Phe-Phe sequence were examineD in the octapeptiDe AGRP-DeriveD macrocyclic scaffolD c[Pro-Arg-Phe-Phe-Xxx-Ala-Phe-DPro], where Xxx was Asn or Diaminopropionic aciD (Dap). Macrocyclic peptiDes were synthesizeD with one, two, or three resiDues of the Arg-Phe-Phe sequence substituteD with the corresponDing D-Isomer(s), generating a 14 compounD library. While l-to-D inversions of the Arg-Phe-Phe sequence in a 20-resiDue AGRP-DeriveD liganD previously resulteD in agonist activity at the MC1R, MC3R, MC4R, anD MC5R, only the MC1R was consistently stimulateD by the macrocycl...
James B Duhadaway - One of the best experts on this subject based on the ideXlab platform.
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inhibition of inDoleamine 2 3 Dioxygenase in DenDritic cells by stereoIsomers of 1 methyl tryptophan correlates with antitumor responses
Cancer Research, 2007Co-Authors: De Yan Hou, Alexander J Muller, Madhav D Sharma, James B Duhadaway, Tinku Banerjee, Maribeth H Johnson, Andrew L Mellor, George C Prendergast, David H MunnAbstract:InDoleamine 2,3-Dioxygenase (IDO) is an immunosuppressive enzyme that contributes to tolerance in a number of biological settings. In cancer, IDO activity may help promote acquireD tolerance to tumor antigens. The IDO inhibitor 1-methyl-tryptophan is being DevelopeD for clinical trials. However, 1-methyl-tryptophan exists in two stereoIsomers with potentially Different biological properties, anD it has been unclear which Isomer might be preferable for initial Development. In this stuDy, we proviDe eviDence that the D anD L stereoIsomers exhibit important cell type-specific variations in activity. The L Isomer was the more potent inhibitor of IDO activity using the purifieD enzyme anD in HeLa cell-baseD assays. However, the D Isomer was significantly more effective in reversing the suppression of T cells createD by IDO-expressing DenDritic cells, using both human monocyte-DeriveD DenDritic cells anD murine DenDritic cells isolateD Directly from tumor-Draining lymph noDes. In vivo, the D Isomer was more efficacious as an anticancer agent in chemo-immunotherapy regimens using cyclophosphamiDe, paclitaxel, or gemcitabine, when testeD in mouse moDels of transplantable melanoma anD transplantable anD autochthonous breast cancer. The D Isomer of 1-methyl-tryptophan specifically targeteD the IDO gene because the antitumor effect of D-1-methyl-tryptophan was completely lost in mice with a Disruption of the IDO gene (IDO-knockout mice). Taken together, our finDings support the suitability of D-1-methyl-tryptophan for human trials aiming to assess the utility of IDO inhibition to block host-meDiateD immunosuppression anD enhance antitumor immunity in the setting of combineD chemo-immunotherapy regimens.
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inhibition of inDoleamine 2 3 Dioxygenase in DenDritic cells by stereoIsomers of 1 methyl tryptophan correlates with antitumor responses
Cancer Research, 2007Co-Authors: Alexander J Muller, Madhav D Sharma, James B Duhadaway, Tinku Banerjee, Maribeth H Johnson, Andrew L Mellor, George C Prendergast, David H MunnAbstract:InDoleamine 2,3-Dioxygenase (IDO) is an immunosuppressive enzyme that contributes to tolerance in a number of biological settings. In cancer, IDO activity may help promote acquireD tolerance to tumor antigens. The IDO inhibitor 1-methyl-tryptophan is being DevelopeD for clinical trials. However, 1-methyl-tryptophan exists in two stereoIsomers with potentially Different biological properties, anD it has been unclear which Isomer might be preferable for initial Development. In this stuDy, we proviDe eviDence that the D anD l stereoIsomers exhibit important cell type–specific variations in activity. The l Isomer was the more potent inhibitor of IDO activity using the purifieD enzyme anD in HeLa cell–baseD assays. However, the D Isomer was significantly more effective in reversing the suppression of T cells createD by IDO-expressing DenDritic cells, using both human monocyte–DeriveD DenDritic cells anD murine DenDritic cells isolateD Directly from tumor-Draining lymph noDes. In vivo , the D Isomer was more efficacious as an anticancer agent in chemo-immunotherapy regimens using cyclophosphamiDe, paclitaxel, or gemcitabine, when testeD in mouse moDels of transplantable melanoma anD transplantable anD autochthonous breast cancer. The D Isomer of 1-methyl-tryptophan specifically targeteD the IDO gene because the antitumor effect of D-1-methyl-tryptophan was completely lost in mice with a Disruption of the IDO gene (IDO-knockout mice). Taken together, our finDings support the suitability of D-1-methyl-tryptophan for human trials aiming to assess the utility of IDO inhibition to block host-meDiateD immunosuppression anD enhance antitumor immunity in the setting of combineD chemo-immunotherapy regimens. [Cancer Res 2007;67(2):792–801]
