The Experts below are selected from a list of 132 Experts worldwide ranked by ideXlab platform
Cédric Boyère - One of the best experts on this subject based on the ideXlab platform.
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Piperidinyl-embeded chalcones possessing anti PI3Kδ inhibitory properties exhibit anti-atopic properties in preclinical models.
European journal of medicinal chemistry, 2018Co-Authors: Charles Dumontet, Guillaume Beck, Fabrice Gardebien, Romain Haudecoeur, Doriane Mathé, Eva-laure Matera, Anne Tourette, Eve Mattei, Justine Esmenjaud, Cédric BoyèreAbstract:Phosphatidylinositide 3-kinases (PI3Ks) are widely expressed enzymes involved in membrane signalization pathways. Attempts to administer inhibitors with broad activity against different isoforms have failed due to toxicity. Conversely the PI3Kδ isoform is much more selectively expressed, enabling therapeutic targeting of this isoform. Of particular interest PI3Kδ is expressed in human Basophils and its inhibition has been shown to reduce anti-IgE induced Basophil Degranulation, suggesting that PI3Kδ inhibitors could be useful as anti-allergy drugs. Herein, we report for the first time the activity of compounds derived from chalcone scaffolds as inhibitors of normal human Basophil Degranulation and identified the most active compound with anti-PI3Kδ properties that was investigated in preclinical models. Compound 18, namely 1-[2-hydroxy-4,6-dimethoxy-3-(N-methylpiperidin-4-yl)phenyl]-3-(2,4,6-trimethoxyphenyl)-prop-2-en-1-one, was found to inhibit normal human Basophil Degranulation in a dose-dependent manner. In a murine model of ovalbumin-induced asthma, compound 18 was shown to reduce expiratory pressure while its impact on the inflammatory infiltrate in alveolar lavage and total lung was dependent on the route of administration. In a DNFB-induced model of atopic dermatitis compound 18 administered systemically proved to be as potent as topical betamethasone. These results support the anti-atopic and allergic properties of the title compound and warrant further clinical development.
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Piperidinyl-embeded chalcones possessing anti PI3K delta inhibitory properties exhibit anti-atopic properties in preclinical models
European Journal of Medicinal Chemistry, 2018Co-Authors: Charles Dumontet, Guillaume Beck, Fabrice Gardebien, Romain Haudecoeur, Eva-laure Matera, Anne Tourette, Eve Mattei, Justine Esmenjaud, Doriane Mahe, Cédric BoyèreAbstract:Phosphatidylinositide 3-kinases (PI3Ks) are widely expressed enzymes involved in membrane signalization pathways. Attempts to administer inhibitors with broad activity against different isoforms have failed due to toxicity. Conversely the PI3K delta isoform is much more selectively expressed, enabling therapeutic targeting of this isoform. Of particular interest PI3K delta is expressed in human Basophils and its inhibition has been shown to reduce anti-IgE induced Basophil Degranulation, suggesting that PI3K delta inhibitors could be useful as anti-allergy drugs. Herein, we report for the first time the activity of compounds derived from chalcone scaffolds as inhibitors of normal human Basophil Degranulation and identified the most active compound with anti-PI3K delta properties that was investigated in preclinical models. Compound 18, namely 1-[2-hydroxy-4,6-dimethoxy-3-(N-methylpiperidin-4-yl)pheny1]-3(2,4,6-trimethoxypheny1)-prop-2-en-1-one, was found to inhibit normal human Basophil Degranulation in a dose-dependent manner. In a murine model of ovalbumin-induced asthma, compound 18 was shown to reduce expiratory pressure while its impact on the inflammatory infiltrate in alveolar lavage and total lung was dependent on the route of administration. In a DNFB-induced model of atopic dermatitis compound 18 administered systemically proved to be as potent as topical betamethasone. These results support the anti-atopic and allergic properties of the title compound and warrant further clinical development. (C) 2018 Elsevier Masson SAS
Esther Von Stebut - One of the best experts on this subject based on the ideXlab platform.
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interleukin 2 immediate type hypersensitivity
Journal Der Deutschen Dermatologischen Gesellschaft, 2008Co-Authors: Peri Caucig, Susanne Lescau, Jurgen Knop, Marcus Maurer, Esther Von StebutAbstract:Summary Two patients with metastatic malignant melanoma developed immediate type hypersensitivity-like symptoms while being treated with recombinant interleukin-(IL-)2 immunotherapy. Both patients showed positive skin prick tests to IL-2, enhanced Basophil Degranulation in vitro and responded to anti-histamines, but laboratory investigations suggested an IgE-independent, pseudoallergic mast cell Degranulation against IL-2.
Charles Dumontet - One of the best experts on this subject based on the ideXlab platform.
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Piperidinyl-embeded chalcones possessing anti PI3Kδ inhibitory properties exhibit anti-atopic properties in preclinical models.
European journal of medicinal chemistry, 2018Co-Authors: Charles Dumontet, Guillaume Beck, Fabrice Gardebien, Romain Haudecoeur, Doriane Mathé, Eva-laure Matera, Anne Tourette, Eve Mattei, Justine Esmenjaud, Cédric BoyèreAbstract:Phosphatidylinositide 3-kinases (PI3Ks) are widely expressed enzymes involved in membrane signalization pathways. Attempts to administer inhibitors with broad activity against different isoforms have failed due to toxicity. Conversely the PI3Kδ isoform is much more selectively expressed, enabling therapeutic targeting of this isoform. Of particular interest PI3Kδ is expressed in human Basophils and its inhibition has been shown to reduce anti-IgE induced Basophil Degranulation, suggesting that PI3Kδ inhibitors could be useful as anti-allergy drugs. Herein, we report for the first time the activity of compounds derived from chalcone scaffolds as inhibitors of normal human Basophil Degranulation and identified the most active compound with anti-PI3Kδ properties that was investigated in preclinical models. Compound 18, namely 1-[2-hydroxy-4,6-dimethoxy-3-(N-methylpiperidin-4-yl)phenyl]-3-(2,4,6-trimethoxyphenyl)-prop-2-en-1-one, was found to inhibit normal human Basophil Degranulation in a dose-dependent manner. In a murine model of ovalbumin-induced asthma, compound 18 was shown to reduce expiratory pressure while its impact on the inflammatory infiltrate in alveolar lavage and total lung was dependent on the route of administration. In a DNFB-induced model of atopic dermatitis compound 18 administered systemically proved to be as potent as topical betamethasone. These results support the anti-atopic and allergic properties of the title compound and warrant further clinical development.
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Piperidinyl-embeded chalcones possessing anti PI3K delta inhibitory properties exhibit anti-atopic properties in preclinical models
European Journal of Medicinal Chemistry, 2018Co-Authors: Charles Dumontet, Guillaume Beck, Fabrice Gardebien, Romain Haudecoeur, Eva-laure Matera, Anne Tourette, Eve Mattei, Justine Esmenjaud, Doriane Mahe, Cédric BoyèreAbstract:Phosphatidylinositide 3-kinases (PI3Ks) are widely expressed enzymes involved in membrane signalization pathways. Attempts to administer inhibitors with broad activity against different isoforms have failed due to toxicity. Conversely the PI3K delta isoform is much more selectively expressed, enabling therapeutic targeting of this isoform. Of particular interest PI3K delta is expressed in human Basophils and its inhibition has been shown to reduce anti-IgE induced Basophil Degranulation, suggesting that PI3K delta inhibitors could be useful as anti-allergy drugs. Herein, we report for the first time the activity of compounds derived from chalcone scaffolds as inhibitors of normal human Basophil Degranulation and identified the most active compound with anti-PI3K delta properties that was investigated in preclinical models. Compound 18, namely 1-[2-hydroxy-4,6-dimethoxy-3-(N-methylpiperidin-4-yl)pheny1]-3(2,4,6-trimethoxypheny1)-prop-2-en-1-one, was found to inhibit normal human Basophil Degranulation in a dose-dependent manner. In a murine model of ovalbumin-induced asthma, compound 18 was shown to reduce expiratory pressure while its impact on the inflammatory infiltrate in alveolar lavage and total lung was dependent on the route of administration. In a DNFB-induced model of atopic dermatitis compound 18 administered systemically proved to be as potent as topical betamethasone. These results support the anti-atopic and allergic properties of the title compound and warrant further clinical development. (C) 2018 Elsevier Masson SAS
Leonardo Greiding - One of the best experts on this subject based on the ideXlab platform.
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Idiopathic chronic urticaria: Comparison between intradermal skin test and TDBH (human Basophils Degranulation test)
Journal of Allergy and Clinical Immunology, 2002Co-Authors: Zulma Liliana Morales, Viviana Segui, Jose Egidio Fabiani, Leonardo GreidingAbstract:54 Idiopathic Chronic Urticaria: Comparison Between Intradermal Skin Test and TDBH (Human Basophils Degranulation Test) Zulma Liliana Morales, Viviana Segui, Jose Egidio Fabiani, Leonardo Greiding Argentine Institute of Allergy and Immunology, Buenos Aires, Argentina URTICARIA AND AUTOANTIBODIES: In 1991 Greaves reported that intradermal injection of autologous sera obtained from patients with chronic urticaria could give inmediate positive results. Several groups have confirmed and extended the original observation of Greaves, demonstrated that 37% of IgG isolated from chronic urticaria patients exhibited autoreactivity against FCe R1. OBJECTIVE: Compare the results of intradermal test with autologous sera with percentage of Basophil Degranulation, induced with those sera. METHODS: Total of 22 patients with ICU. Intradermal test with autologous sera: 0,05 cc compared with fisiologic solution witness. We consider positive test when the difference is > 1,5 mm. TDBH (Human Basophil Degranulation Test) concentrated sera and dilutions 1/10, 1/100, 1/1000 (Grinstein and Simkin Technic). Re-count and percentage of witness Basophil Degranulation. RESULTS: Positive lntradermal Test: 14/22 patients. Percents of Basophil Degranulation: 21-29-18-11-16-19-19-12-33-40-26-18-24-25, X= 22,2. Negative Intradermal Test: 8/22 patients. Percents of Basophil Degranulation: 22-17-19-14-22-18-19-7, X= 17,2. Fischer Test: p = 0,0981. CONCLUSION: The difference between positive and negative intradermal test and TDBH are, to this number of patients no significative, most number of patients could give us a definitive statistic relation.
Peri Caucig - One of the best experts on this subject based on the ideXlab platform.
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interleukin 2 immediate type hypersensitivity
Journal Der Deutschen Dermatologischen Gesellschaft, 2008Co-Authors: Peri Caucig, Susanne Lescau, Jurgen Knop, Marcus Maurer, Esther Von StebutAbstract:Summary Two patients with metastatic malignant melanoma developed immediate type hypersensitivity-like symptoms while being treated with recombinant interleukin-(IL-)2 immunotherapy. Both patients showed positive skin prick tests to IL-2, enhanced Basophil Degranulation in vitro and responded to anti-histamines, but laboratory investigations suggested an IgE-independent, pseudoallergic mast cell Degranulation against IL-2.