The Experts below are selected from a list of 30738 Experts worldwide ranked by ideXlab platform
Keith Biggadike - One of the best experts on this subject based on the ideXlab platform.
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correlation of skin blanching and percutaneous absorption for glucocorticoid receptor agonists by matrix assisted laser desorption ionization mass spectrometry imaging and liquid extraction surface analysis with nanoelectrospray ionization mass spectrometry
Analytical Chemistry, 2010Co-Authors: Peter S Marshall, Valerie Toteudjomte, Philippe Bareille, Hayley Perry, Gillian Brown, Mark Baumert, Keith BiggadikeAbstract:Matrix-assisted laser desorption/ionization-mass spectrometry imaging (MALDI-MSI) and liquid extraction surface analysis (LESA) with nanoelectrospray ionization mass spectrometry (nESI-MS) have both been successfully employed to determine the degree of percutaneous absorption of three novel nonsteroid glucocorticoid receptor (GR) agonists in porcine ear sections. Historically, the ability of a glucocorticoid to elicit a skin blanching response when applied at low dose in ethanol solution to the forearms of healthy human volunteers has been a reliable predictor of their Topical Anti-Inflammatory activity. While all three nonsteroidal GR agonists under investigation caused a skin blanching effect, the responses did not correlate with in vitro GR agonist potencies and different time courses were also observed for the skin blanching responses. MALDI MSI and LESA with nESI-MS were used to investigate and understand these different responses. The findings of the investigation was that the depth of porcine skin ...
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correlation of skin blanching and percutaneous absorption for glucocorticoid receptor agonists by matrix assisted laser desorption ionization mass spectrometry imaging and liquid extraction surface analysis with nanoelectrospray ionization mass spectrometry
Analytical Chemistry, 2010Co-Authors: Peter S Marshall, Valerie Toteudjomte, Philippe Bareille, Hayley Perry, Gillian Brown, Mark Baumert, Keith BiggadikeAbstract:Matrix-assisted laser desorption/ionization-mass spectrometry imaging (MALDI-MSI) and liquid extraction surface analysis (LESA) with nanoelectrospray ionization mass spectrometry (nESI-MS) have both been successfully employed to determine the degree of percutaneous absorption of three novel nonsteroid glucocorticoid receptor (GR) agonists in porcine ear sections. Historically, the ability of a glucocorticoid to elicit a skin blanching response when applied at low dose in ethanol solution to the forearms of healthy human volunteers has been a reliable predictor of their Topical Anti-Inflammatory activity. While all three nonsteroidal GR agonists under investigation caused a skin blanching effect, the responses did not correlate with in vitro GR agonist potencies and different time courses were also observed for the skin blanching responses. MALDI MSI and LESA with nESI-MS were used to investigate and understand these different responses. The findings of the investigation was that the depth of porcine skin penetration correlates to the degree of skin blanching obtained for the same three compounds in human volunteers.
Peter S Marshall - One of the best experts on this subject based on the ideXlab platform.
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correlation of skin blanching and percutaneous absorption for glucocorticoid receptor agonists by matrix assisted laser desorption ionization mass spectrometry imaging and liquid extraction surface analysis with nanoelectrospray ionization mass spectrometry
Analytical Chemistry, 2010Co-Authors: Peter S Marshall, Valerie Toteudjomte, Philippe Bareille, Hayley Perry, Gillian Brown, Mark Baumert, Keith BiggadikeAbstract:Matrix-assisted laser desorption/ionization-mass spectrometry imaging (MALDI-MSI) and liquid extraction surface analysis (LESA) with nanoelectrospray ionization mass spectrometry (nESI-MS) have both been successfully employed to determine the degree of percutaneous absorption of three novel nonsteroid glucocorticoid receptor (GR) agonists in porcine ear sections. Historically, the ability of a glucocorticoid to elicit a skin blanching response when applied at low dose in ethanol solution to the forearms of healthy human volunteers has been a reliable predictor of their Topical Anti-Inflammatory activity. While all three nonsteroidal GR agonists under investigation caused a skin blanching effect, the responses did not correlate with in vitro GR agonist potencies and different time courses were also observed for the skin blanching responses. MALDI MSI and LESA with nESI-MS were used to investigate and understand these different responses. The findings of the investigation was that the depth of porcine skin ...
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correlation of skin blanching and percutaneous absorption for glucocorticoid receptor agonists by matrix assisted laser desorption ionization mass spectrometry imaging and liquid extraction surface analysis with nanoelectrospray ionization mass spectrometry
Analytical Chemistry, 2010Co-Authors: Peter S Marshall, Valerie Toteudjomte, Philippe Bareille, Hayley Perry, Gillian Brown, Mark Baumert, Keith BiggadikeAbstract:Matrix-assisted laser desorption/ionization-mass spectrometry imaging (MALDI-MSI) and liquid extraction surface analysis (LESA) with nanoelectrospray ionization mass spectrometry (nESI-MS) have both been successfully employed to determine the degree of percutaneous absorption of three novel nonsteroid glucocorticoid receptor (GR) agonists in porcine ear sections. Historically, the ability of a glucocorticoid to elicit a skin blanching response when applied at low dose in ethanol solution to the forearms of healthy human volunteers has been a reliable predictor of their Topical Anti-Inflammatory activity. While all three nonsteroidal GR agonists under investigation caused a skin blanching effect, the responses did not correlate with in vitro GR agonist potencies and different time courses were also observed for the skin blanching responses. MALDI MSI and LESA with nESI-MS were used to investigate and understand these different responses. The findings of the investigation was that the depth of porcine skin penetration correlates to the degree of skin blanching obtained for the same three compounds in human volunteers.
Lee T Zane - One of the best experts on this subject based on the ideXlab platform.
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a novel nonsteroidal Topical anti inflammatory phosphodiesterase 4 inhibitor crisaborole ointment reduced pruritus and signs of atopic dermatitis in 2 phase 3 studies in children and adults
Pediatrics, 2018Co-Authors: Adelaide A Hebert, Mark Lebwohl, Lawrence F Eichenfield, Amy S Paller, Eric L Simpson, Wynnis L Tom, Matilda H Hughes, Lee T ZaneAbstract:Background: Atopic dermatitis (AD) is an inflammatory skin disease that presents with intense pruritus and red, inflamed lesions. Crisaborole Topical Ointment, 2% (Anacor Pharmaceuticals, Palo Alto, CA), is an investigational, nonsteroidal, Topical Anti-Inflammatory, phosphodiesterase 4 inhibitor for the treatment of AD. Objective: To evaluate the additional predefined efficacy endpoints on the impact of crisaborole ointment on pruritus and signs of AD from 2 Phase …
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two phase 3 study results of children and adults with mild to moderate atopic dermatitis treated with crisaborole Topical ointment 2 a novel nonsteroidal Topical anti inflammatory phosphodiesterase 4 inhibitor
Journal of Immunology, 2016Co-Authors: Lee T Zane, Mark Lebwohl, Lawrence F Eichenfield, Amy S Paller, Wynnis L Tom, Robin L Blumenthal, Mark Boguniewicz, Robert S Call, Douglass W Forsha, William C ReesAbstract:Up to 90% of children and adults with atopic dermatitis (AD), a chronic inflammatory skin disease, present with mild-to-moderate disease. Crisaborole Topical Ointment, 2%, is a novel, nonsteroidal, Topical, Anti-Inflammatory, phosphodiesterase 4 inhibitor being studied for the treatment of AD. The efficacy and safety of crisaborole was assessed in 2 identically designed, multicenter, vehicle-controlled, double-blind Phase 3 studies (301 and 302) that enrolled patients ≥2 years old with mild-to-moderate AD affecting ≥5% of body surface area (BSA). Patients were randomized 2:1 to receive crisaborole or vehicle twice daily and evaluated on Days 8, 15, 22, and 29. The primary endpoint defined success in the Investigator’s Static Global Assessment (ISGA) as “almost clear/1” or “clear/0” with ≥2-grade improvement from baseline at Day 29. Secondary endpoints analyzed the time to success and the percentage of patients achieving “almost clear/1” or “clear/0” on ISGA. At Day 29, more crisaborole-treated patients achieved ISGA success than vehicle (301: 32.8% vs 25.4%, P = 0.038; 302: 31.4% vs 18.0%, P P = 0.005; 302: 48.5% vs 29.7%, P P
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crisaborole Topical ointment 2 a nonsteroidal Topical anti inflammatory phosphodiesterase 4 inhibitor in clinical development for the treatment of atopic dermatitis
Journal of Drugs in Dermatology, 2016Co-Authors: Kurt Jarnagin, Lee T Zane, Sanjay Chanda, Dina Coronado, E Guttmanyassky, Mark LebwohlAbstract:Crisaborole Topical ointment, 2% (formerly known as AN2728) is a benzoxaborole, nonsteroidal, Topical, Anti-Inflammatory phosphodiesterase 4 (PDE4) inhibitor investigational compound that recently completed phase 3 studies for the treatment of mild to moderate atopic dermatitis (AD). The unique configuration of boron within the crisaborole molecule enables selective targeting and inhibition of PDE4, an enzyme that converts the intracellular second messenger 3'5'-cyclic adenosine monophosphate (cAMP) into the active metabolite adenosine monophosphate (AMP). By inhibiting PDE4 and thus increasing levels of cAMP, crisaborole controls inflammation. The use of boron chemistry enabled synthesis of a low-molecular-weight compound (251 daltons), thereby facilitating effective penetration of crisaborole through human skin. In vitro experiments showed that crisaborole inhibits cytokine production from peripheral blood mononuclear cells in a pattern similar to other PDE4 inhibitors and distinct from corticosteroids. Crisaborole also displayed Topical Anti-Inflammatory activity in a skin inflammation model. Once crisaborole reaches systemic circulation after Topical application, it is metabolized to inactive metabolites. This limits systemic exposure to crisaborole and systemic PDE4 inhibition. In phase 1 and 2 clinical studies, crisaborole ointment, 2% was generally well tolerated and improved AD disease severity scores, pruritus, and all other AD signs and symptoms. Two large, randomized, controlled, phase 3, pivotal clinical trials assessing the efficacy and safety of crisaborole Topical ointment, 2% in children, adolescents, and adults with mild to moderate AD were recently completed with positive results.
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an2728 a new boron based Topical anti inflammatory agent inhibits phosphodiesterase 4 irc4p 611
Journal of Immunology, 2015Co-Authors: Yvonne Freund, Chen Dong, Charlotte Virtuciofrates, Fernando Rock, Yvonne Mak, Yasheen Zhou, Lee T Zane, Kurt JarnaginAbstract:The novel boron-containing compound, AN2728, is being investigated in phase 3 trials for atopic dermatitis treatment. It exerts its Anti-Inflammatory effect by inhibiting phosphodiesterase-4 (PDE4), which catalyzes the breakdown of cAMP to AMP. AN2728 competes with cAMP to inhibit the PDE4B1-catalytic domain with Ki of 173±26 nM; thus AN2728 interacts at the enzyme-active site. The X-ray structure of PDE4B-catalytic domain with AN2728 and its structural relative AN2898 reveals that the boron atom interacts with the bimetal center and occupies a position in the catalytic site similar to that of the cAMP phosphate. AN2728 has good affinity across PDE4 gene products A-D. Its selective affinity for PDE4 is 4-10-fold greater than its affinity for PDE1, 2, 3A, 6, or 7B. It is inactive on PDE3B, 5, 7A1, and 8-11. AN2728 activity increases intracellular cAMP and activates PKA, followed by phosphorylation and negative regulation of various cytokine transcription factors. AN2728 inhibits production of specific cytokines with a pattern similar to that of other established PDE4 inhibitors and distinct from those of a glucocorticoid and calcineurin inhibitor. To investigate reactivity against other targets, AN2728 was tested against a set of 50 receptors and ligand-gated ion channels for inhibition at 10 µM. Inhibition was <25% for all receptors; thus, AN2728 is specific for PDE4 and appears to exert an Anti-Inflammatory effect through inhibition of inflammatory cytokine production.
Gillian Brown - One of the best experts on this subject based on the ideXlab platform.
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correlation of skin blanching and percutaneous absorption for glucocorticoid receptor agonists by matrix assisted laser desorption ionization mass spectrometry imaging and liquid extraction surface analysis with nanoelectrospray ionization mass spectrometry
Analytical Chemistry, 2010Co-Authors: Peter S Marshall, Valerie Toteudjomte, Philippe Bareille, Hayley Perry, Gillian Brown, Mark Baumert, Keith BiggadikeAbstract:Matrix-assisted laser desorption/ionization-mass spectrometry imaging (MALDI-MSI) and liquid extraction surface analysis (LESA) with nanoelectrospray ionization mass spectrometry (nESI-MS) have both been successfully employed to determine the degree of percutaneous absorption of three novel nonsteroid glucocorticoid receptor (GR) agonists in porcine ear sections. Historically, the ability of a glucocorticoid to elicit a skin blanching response when applied at low dose in ethanol solution to the forearms of healthy human volunteers has been a reliable predictor of their Topical Anti-Inflammatory activity. While all three nonsteroidal GR agonists under investigation caused a skin blanching effect, the responses did not correlate with in vitro GR agonist potencies and different time courses were also observed for the skin blanching responses. MALDI MSI and LESA with nESI-MS were used to investigate and understand these different responses. The findings of the investigation was that the depth of porcine skin ...
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correlation of skin blanching and percutaneous absorption for glucocorticoid receptor agonists by matrix assisted laser desorption ionization mass spectrometry imaging and liquid extraction surface analysis with nanoelectrospray ionization mass spectrometry
Analytical Chemistry, 2010Co-Authors: Peter S Marshall, Valerie Toteudjomte, Philippe Bareille, Hayley Perry, Gillian Brown, Mark Baumert, Keith BiggadikeAbstract:Matrix-assisted laser desorption/ionization-mass spectrometry imaging (MALDI-MSI) and liquid extraction surface analysis (LESA) with nanoelectrospray ionization mass spectrometry (nESI-MS) have both been successfully employed to determine the degree of percutaneous absorption of three novel nonsteroid glucocorticoid receptor (GR) agonists in porcine ear sections. Historically, the ability of a glucocorticoid to elicit a skin blanching response when applied at low dose in ethanol solution to the forearms of healthy human volunteers has been a reliable predictor of their Topical Anti-Inflammatory activity. While all three nonsteroidal GR agonists under investigation caused a skin blanching effect, the responses did not correlate with in vitro GR agonist potencies and different time courses were also observed for the skin blanching responses. MALDI MSI and LESA with nESI-MS were used to investigate and understand these different responses. The findings of the investigation was that the depth of porcine skin penetration correlates to the degree of skin blanching obtained for the same three compounds in human volunteers.
Valerie Toteudjomte - One of the best experts on this subject based on the ideXlab platform.
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correlation of skin blanching and percutaneous absorption for glucocorticoid receptor agonists by matrix assisted laser desorption ionization mass spectrometry imaging and liquid extraction surface analysis with nanoelectrospray ionization mass spectrometry
Analytical Chemistry, 2010Co-Authors: Peter S Marshall, Valerie Toteudjomte, Philippe Bareille, Hayley Perry, Gillian Brown, Mark Baumert, Keith BiggadikeAbstract:Matrix-assisted laser desorption/ionization-mass spectrometry imaging (MALDI-MSI) and liquid extraction surface analysis (LESA) with nanoelectrospray ionization mass spectrometry (nESI-MS) have both been successfully employed to determine the degree of percutaneous absorption of three novel nonsteroid glucocorticoid receptor (GR) agonists in porcine ear sections. Historically, the ability of a glucocorticoid to elicit a skin blanching response when applied at low dose in ethanol solution to the forearms of healthy human volunteers has been a reliable predictor of their Topical Anti-Inflammatory activity. While all three nonsteroidal GR agonists under investigation caused a skin blanching effect, the responses did not correlate with in vitro GR agonist potencies and different time courses were also observed for the skin blanching responses. MALDI MSI and LESA with nESI-MS were used to investigate and understand these different responses. The findings of the investigation was that the depth of porcine skin ...
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correlation of skin blanching and percutaneous absorption for glucocorticoid receptor agonists by matrix assisted laser desorption ionization mass spectrometry imaging and liquid extraction surface analysis with nanoelectrospray ionization mass spectrometry
Analytical Chemistry, 2010Co-Authors: Peter S Marshall, Valerie Toteudjomte, Philippe Bareille, Hayley Perry, Gillian Brown, Mark Baumert, Keith BiggadikeAbstract:Matrix-assisted laser desorption/ionization-mass spectrometry imaging (MALDI-MSI) and liquid extraction surface analysis (LESA) with nanoelectrospray ionization mass spectrometry (nESI-MS) have both been successfully employed to determine the degree of percutaneous absorption of three novel nonsteroid glucocorticoid receptor (GR) agonists in porcine ear sections. Historically, the ability of a glucocorticoid to elicit a skin blanching response when applied at low dose in ethanol solution to the forearms of healthy human volunteers has been a reliable predictor of their Topical Anti-Inflammatory activity. While all three nonsteroidal GR agonists under investigation caused a skin blanching effect, the responses did not correlate with in vitro GR agonist potencies and different time courses were also observed for the skin blanching responses. MALDI MSI and LESA with nESI-MS were used to investigate and understand these different responses. The findings of the investigation was that the depth of porcine skin penetration correlates to the degree of skin blanching obtained for the same three compounds in human volunteers.
