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Daniel M Sheehan - One of the best experts on this subject based on the ideXlab platform.

  • the estrogen receptor relative Binding affinities of 188 natural and xenochemicals structural diversity of ligands
    Toxicological Sciences, 2000
    Co-Authors: R Blair, Hong Fang, William S Branham, Bruce S Hass, Stacey L Dial, Carrie L Moland, Weida Tong, Roger Perkins, Daniel M Sheehan
    Abstract:

    We have utilized a validated (standardized) estrogen receptor (ER) Competitive-Binding Assay to determine the ER affinity for a large, structurally diverse group of chemicals. Uteri from ovariectomized Sprague-Dawley rats were the ER source for the Competitive-Binding Assay. Initially, test chemicals were screened at high concentrations to determine whether a chemical competed with [ 3 H]-estradiol for the ER. Test chemicals that exhibited affinity for the ER in the first tier were subsequently Assayed using a wide range of concentrations to characterize the Binding curve and to determine each chemical’s IC50 and relative Binding affinity (RBA) values. Overall, we Assayed 188 chemicals, covering a 1 3 10 6 -fold range of RBAs from several different chemical or use categories, including steroidal estrogens, synthetic estrogens, antiestrogens, other miscellaneous steroids, alkylphenols, diphenyl derivatives, organochlorines, pesticides, alkylhydroxybenzoate preservatives (parabens), phthalates, benzophenone compounds, and a number of other miscellaneous chemicals. Of the 188 chemicals tested, 100 bound to the ER while 88 were non-binders. Included in the 100 chemicals that bound to the ER were 4-benzyloxyphenol, 2,4dihydroxybenzophenone, and 2,2*-methylenebis(4-chlorophenol), compounds that have not been shown previously to bind the ER. It was also evident that certain structural features, such as an overall ring structure, were important for ER Binding. The current study provides the most structurally diverse ER RBA data set with

  • the estrogen receptor relative Binding affinities of 188 natural and xenochemicals structural diversity of ligands
    Toxicological Sciences, 2000
    Co-Authors: R Blair, Hong Fang, William S Branham, Bruce S Hass, Stacey L Dial, Carrie L Moland, Weida Tong, Roger Perkins, Leming Shi, Daniel M Sheehan
    Abstract:

    We have utilized a validated (standardized) estrogen receptor (ER) Competitive-Binding Assay to determine the ER affinity for a large, structurally diverse group of chemicals. Uteri from ovariectomized Sprague-Dawley rats were the ER source for the Competitive-Binding Assay. Initially, test chemicals were screened at high concentrations to determine whether a chemical competed with [3H]-estradiol for the ER. Test chemicals that exhibited affinity for the ER in the first tier were subsequently Assayed using a wide range of concentrations to characterize the Binding curve and to determine each chemical's IC50 and relative Binding affinity (RBA) values. Overall, we Assayed 188 chemicals, covering a 1 x 10(6)-fold range of RBAs from several different chemical or use categories, including steroidal estrogens, synthetic estrogens, antiestrogens, other miscellaneous steroids, alkylphenols, diphenyl derivatives, organochlorines, pesticides, alkylhydroxybenzoate preservatives (parabens), phthalates, benzophenone compounds, and a number of other miscellaneous chemicals. Of the 188 chemicals tested, 100 bound to the ER while 88 were non-binders. Included in the 100 chemicals that bound to the ER were 4-benzyloxyphenol, 2,4-dihydroxybenzophenone, and 2,2'-methylenebis(4-chlorophenol), compounds that have not been shown previously to bind the ER. It was also evident that certain structural features, such as an overall ring structure, were important for ER Binding. The current study provides the most structurally diverse ER RBA data set with the widest range of RBA values published to date.

Atsushi Tomonaga - One of the best experts on this subject based on the ideXlab platform.

  • identification of allosteric erk2 inhibitors through in silico biased screening and Competitive Binding Assay
    Bioorganic & Medicinal Chemistry Letters, 2016
    Co-Authors: Takayoshi Kinoshita, Hajime Sugiyama, Yurika Mori, Naruhide Takahashi, Atsushi Tomonaga
    Abstract:

    Extracellular signal-regulated kinase 2 (ERK2) is a drug target for type 2 diabetes mellitus. A peptide-type ERK2 inhibitor (PEP) was discovered in the previous study through the knowledge-based method and showed physiological effects on the db/db mice model of type 2 diabetes. Here, the crystal structure showed that PEP bound to the allosteric site without the interruption of the ATP Competitive inhibitor Binding to ERK2. An in silico biased-screening using the focused library rendered three compounds with inhibitory activity of IC50 <100 μM. Among them, two compounds revealed the concentration-dependent competition with PEP and could be lead compounds for antidiabetic medicine.

  • Identification of allosteric ERK2 inhibitors through in silico biased screening and Competitive Binding Assay.
    Bioorganic & medicinal chemistry letters, 2015
    Co-Authors: Takayoshi Kinoshita, Hajime Sugiyama, Yurika Mori, Naruhide Takahashi, Atsushi Tomonaga
    Abstract:

    Extracellular signal-regulated kinase 2 (ERK2) is a drug target for type 2 diabetes mellitus. A peptide-type ERK2 inhibitor (PEP) was discovered in the previous study through the knowledge-based method and showed physiological effects on the db/db mice model of type 2 diabetes. Here, the crystal structure showed that PEP bound to the allosteric site without the interruption of the ATP Competitive inhibitor Binding to ERK2. An in silico biased-screening using the focused library rendered three compounds with inhibitory activity of IC50

R Blair - One of the best experts on this subject based on the ideXlab platform.

  • the estrogen receptor relative Binding affinities of 188 natural and xenochemicals structural diversity of ligands
    Toxicological Sciences, 2000
    Co-Authors: R Blair, Hong Fang, William S Branham, Bruce S Hass, Stacey L Dial, Carrie L Moland, Weida Tong, Roger Perkins, Daniel M Sheehan
    Abstract:

    We have utilized a validated (standardized) estrogen receptor (ER) Competitive-Binding Assay to determine the ER affinity for a large, structurally diverse group of chemicals. Uteri from ovariectomized Sprague-Dawley rats were the ER source for the Competitive-Binding Assay. Initially, test chemicals were screened at high concentrations to determine whether a chemical competed with [ 3 H]-estradiol for the ER. Test chemicals that exhibited affinity for the ER in the first tier were subsequently Assayed using a wide range of concentrations to characterize the Binding curve and to determine each chemical’s IC50 and relative Binding affinity (RBA) values. Overall, we Assayed 188 chemicals, covering a 1 3 10 6 -fold range of RBAs from several different chemical or use categories, including steroidal estrogens, synthetic estrogens, antiestrogens, other miscellaneous steroids, alkylphenols, diphenyl derivatives, organochlorines, pesticides, alkylhydroxybenzoate preservatives (parabens), phthalates, benzophenone compounds, and a number of other miscellaneous chemicals. Of the 188 chemicals tested, 100 bound to the ER while 88 were non-binders. Included in the 100 chemicals that bound to the ER were 4-benzyloxyphenol, 2,4dihydroxybenzophenone, and 2,2*-methylenebis(4-chlorophenol), compounds that have not been shown previously to bind the ER. It was also evident that certain structural features, such as an overall ring structure, were important for ER Binding. The current study provides the most structurally diverse ER RBA data set with

  • the estrogen receptor relative Binding affinities of 188 natural and xenochemicals structural diversity of ligands
    Toxicological Sciences, 2000
    Co-Authors: R Blair, Hong Fang, William S Branham, Bruce S Hass, Stacey L Dial, Carrie L Moland, Weida Tong, Roger Perkins, Leming Shi, Daniel M Sheehan
    Abstract:

    We have utilized a validated (standardized) estrogen receptor (ER) Competitive-Binding Assay to determine the ER affinity for a large, structurally diverse group of chemicals. Uteri from ovariectomized Sprague-Dawley rats were the ER source for the Competitive-Binding Assay. Initially, test chemicals were screened at high concentrations to determine whether a chemical competed with [3H]-estradiol for the ER. Test chemicals that exhibited affinity for the ER in the first tier were subsequently Assayed using a wide range of concentrations to characterize the Binding curve and to determine each chemical's IC50 and relative Binding affinity (RBA) values. Overall, we Assayed 188 chemicals, covering a 1 x 10(6)-fold range of RBAs from several different chemical or use categories, including steroidal estrogens, synthetic estrogens, antiestrogens, other miscellaneous steroids, alkylphenols, diphenyl derivatives, organochlorines, pesticides, alkylhydroxybenzoate preservatives (parabens), phthalates, benzophenone compounds, and a number of other miscellaneous chemicals. Of the 188 chemicals tested, 100 bound to the ER while 88 were non-binders. Included in the 100 chemicals that bound to the ER were 4-benzyloxyphenol, 2,4-dihydroxybenzophenone, and 2,2'-methylenebis(4-chlorophenol), compounds that have not been shown previously to bind the ER. It was also evident that certain structural features, such as an overall ring structure, were important for ER Binding. The current study provides the most structurally diverse ER RBA data set with the widest range of RBA values published to date.

John Ferkany - One of the best experts on this subject based on the ideXlab platform.

  • Radioligand Binding Assays for the glycine site on N-methyl-D-aspartate receptors.
    Current protocols in pharmacology, 2002
    Co-Authors: Scott Perschke, John Ferkany
    Abstract:

    This unit describes a Competitive Binding Assay for the glycine Binding site on the NMDA subtype of glutamate receptors in rat brain homogenates. Agonists of the NMDA receptor associated glycine Binding site have been proposed as potential therapeutics in cognitive disorders. Conversely, antagonists may be useful in a variety of disorders associated with excessive activation of EAA receptors, including Parkinson, Huntington and Alzheimer Diseases, and neuropathic pain, among others. This unit describes a Competitive Binding Assay for the glycine Binding site on the NMDA subtype of glutamate receptors in rat.

  • Current Protocols in Pharmacology - Radioligand Binding Assays for the Glycine Site on N‐Methyl‐D‐Aspartate Receptors
    Current Protocols in Pharmacology, 2002
    Co-Authors: Scott Perschke, John Ferkany
    Abstract:

    This unit describes a Competitive Binding Assay for the glycine Binding site on the NMDA subtype of glutamate receptors in rat brain homogenates. Agonists of the NMDA receptor associated glycine Binding site have been proposed as potential therapeutics in cognitive disorders. Conversely, antagonists may be useful in a variety of disorders associated with excessive activation of EAA receptors, including Parkinson, Huntington and Alzheimer Diseases, and neuropathic pain, among others. This unit describes a Competitive Binding Assay for the glycine Binding site on the NMDA subtype of glutamate receptors in rat.

Takayoshi Kinoshita - One of the best experts on this subject based on the ideXlab platform.

  • identification of allosteric erk2 inhibitors through in silico biased screening and Competitive Binding Assay
    Bioorganic & Medicinal Chemistry Letters, 2016
    Co-Authors: Takayoshi Kinoshita, Hajime Sugiyama, Yurika Mori, Naruhide Takahashi, Atsushi Tomonaga
    Abstract:

    Extracellular signal-regulated kinase 2 (ERK2) is a drug target for type 2 diabetes mellitus. A peptide-type ERK2 inhibitor (PEP) was discovered in the previous study through the knowledge-based method and showed physiological effects on the db/db mice model of type 2 diabetes. Here, the crystal structure showed that PEP bound to the allosteric site without the interruption of the ATP Competitive inhibitor Binding to ERK2. An in silico biased-screening using the focused library rendered three compounds with inhibitory activity of IC50 <100 μM. Among them, two compounds revealed the concentration-dependent competition with PEP and could be lead compounds for antidiabetic medicine.

  • Identification of allosteric ERK2 inhibitors through in silico biased screening and Competitive Binding Assay.
    Bioorganic & medicinal chemistry letters, 2015
    Co-Authors: Takayoshi Kinoshita, Hajime Sugiyama, Yurika Mori, Naruhide Takahashi, Atsushi Tomonaga
    Abstract:

    Extracellular signal-regulated kinase 2 (ERK2) is a drug target for type 2 diabetes mellitus. A peptide-type ERK2 inhibitor (PEP) was discovered in the previous study through the knowledge-based method and showed physiological effects on the db/db mice model of type 2 diabetes. Here, the crystal structure showed that PEP bound to the allosteric site without the interruption of the ATP Competitive inhibitor Binding to ERK2. An in silico biased-screening using the focused library rendered three compounds with inhibitory activity of IC50