The Experts below are selected from a list of 849 Experts worldwide ranked by ideXlab platform
Gensuke Takayama - One of the best experts on this subject based on the ideXlab platform.
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Improvement of pulmonary function by oral treatment with a VLA-4 antagonist in a mouse asthmatic model.
Journal of pharmacological sciences, 2013Co-Authors: Gensuke Takayama, Mika Yokoyama, Keiko Matsumoto, Tomoe Taira, Misato Aonuma, Yutaka Iigo, Tohru TakashiAbstract:Abstract We investigated in vivo efficacies of the newly synthesized VLA-4 antagonist Compound A { trans -4-[1-[[2,5-Dichloro-4-(1-methyl-3-indolylcarboxamido)phenyl]acetyl]-(4 S )-methoxy-(2 S )-pyrrolidinylmethoxy]cyclohexanecarboxylic acid} on Ascaris antigen–induced airway inflammation and hyperresponsiveness in a murine asthmatic model. Oral administration of Compound A significantly inhibited eosinophil infiltration into BALF and airway hyperresponsiveness 48 h after the antigen challenge. Histologic analysis of the lung sections confirmed the BALF result and revealed suppression of edema and mucus hyperplasia at 8 and 48 h after the challenge, respectively. These findings clearly show that orally active Compound A has therapeutic potential for treatment of asthma.
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Identification of trans-4-[1-[[7-fluoro-2-(1-methyl-3-indolyl)-6-benzoxazolyl]acetyl]-(4S)-fluoro-(2S)-pyrrolidinylmethoxy]cyclohexanecarboxylic acid as a potent, orally active VLA-4 antagonist.
Bioorganic & medicinal chemistry, 2011Co-Authors: Masaki Setoguchi, Jun Chiba, Gensuke Takayama, Yutaka Iigo, Shin Iimura, Yuuichi Sugimoto, Yoshiyuki Yoneda, Toshiyuki Watanabe, Fumihito Muro, Mika YokoyamaAbstract:For the purpose of obtaining orally potent VLA-4 inhibitors, we have carried out structural modification of the (N'-phenylureido)phenyl group in compound 1, where the group was found to be attributed to poor pharmacokinetic profile in our previous research. Through modification, we have identified several compounds with both potent in vitro activity and improved oral exposure. In particular, compound 7e with 7-fluoro-2-(1-methyl-1H-indol-3-yl)-1,3-benzoxazolyl group as a novel replacement of the (N'-phenylureido)phenyl group significantly inhibited eosinophil infiltration into bronchoalveolar lavage fluid at 15mg/kg in an Ascaris-antigen-induced murine bronchial inflammatory model, and its efficacy was comparable to that of the anti-mouse α(4) antibody (R1-2).
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Identified a morpholinyl-4-piperidinylacetic acid derivative as a potent oral active VLA-4 antagonist
Bioorganic & Medicinal Chemistry Letters, 2005Co-Authors: Jun Chiba, Nobuo Machinaga, Tohru Takashi, Akio Ejima, Gensuke Takayama, Mika Yokoyama, Atsushi Nakayama, John J. Baldwin, Edward Mcdonald, Kurt W. SaionzAbstract:Abstract An investigation into the structure–activity relationship of a lead compound, prolyl-5-aminopentanoic acid 4 , led to the identification of a novel series of 4-piperidinylacetic acid, 1-piperazinylacetic acid, and 4-aminobenzoic acid derivatives as potent VLA-4 antagonists with low nanomolar IC 50 values. A representative compound morpholinyl-4-piperidinylacetic acid derivative ( 13d : IC 50 = 4.4 nM) showed efficacy in the Ascaris -antigen sensitized murine airway inflammation model by oral administration.
Tohru Takashi - One of the best experts on this subject based on the ideXlab platform.
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Improvement of pulmonary function by oral treatment with a VLA-4 antagonist in a mouse asthmatic model.
Journal of pharmacological sciences, 2013Co-Authors: Gensuke Takayama, Mika Yokoyama, Keiko Matsumoto, Tomoe Taira, Misato Aonuma, Yutaka Iigo, Tohru TakashiAbstract:Abstract We investigated in vivo efficacies of the newly synthesized VLA-4 antagonist Compound A { trans -4-[1-[[2,5-Dichloro-4-(1-methyl-3-indolylcarboxamido)phenyl]acetyl]-(4 S )-methoxy-(2 S )-pyrrolidinylmethoxy]cyclohexanecarboxylic acid} on Ascaris antigen–induced airway inflammation and hyperresponsiveness in a murine asthmatic model. Oral administration of Compound A significantly inhibited eosinophil infiltration into BALF and airway hyperresponsiveness 48 h after the antigen challenge. Histologic analysis of the lung sections confirmed the BALF result and revealed suppression of edema and mucus hyperplasia at 8 and 48 h after the challenge, respectively. These findings clearly show that orally active Compound A has therapeutic potential for treatment of asthma.
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Identified a morpholinyl-4-piperidinylacetic acid derivative as a potent oral active VLA-4 antagonist
Bioorganic & Medicinal Chemistry Letters, 2005Co-Authors: Jun Chiba, Nobuo Machinaga, Tohru Takashi, Akio Ejima, Gensuke Takayama, Mika Yokoyama, Atsushi Nakayama, John J. Baldwin, Edward Mcdonald, Kurt W. SaionzAbstract:Abstract An investigation into the structure–activity relationship of a lead compound, prolyl-5-aminopentanoic acid 4 , led to the identification of a novel series of 4-piperidinylacetic acid, 1-piperazinylacetic acid, and 4-aminobenzoic acid derivatives as potent VLA-4 antagonists with low nanomolar IC 50 values. A representative compound morpholinyl-4-piperidinylacetic acid derivative ( 13d : IC 50 = 4.4 nM) showed efficacy in the Ascaris -antigen sensitized murine airway inflammation model by oral administration.
Mika Yokoyama - One of the best experts on this subject based on the ideXlab platform.
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Improvement of pulmonary function by oral treatment with a VLA-4 antagonist in a mouse asthmatic model.
Journal of pharmacological sciences, 2013Co-Authors: Gensuke Takayama, Mika Yokoyama, Keiko Matsumoto, Tomoe Taira, Misato Aonuma, Yutaka Iigo, Tohru TakashiAbstract:Abstract We investigated in vivo efficacies of the newly synthesized VLA-4 antagonist Compound A { trans -4-[1-[[2,5-Dichloro-4-(1-methyl-3-indolylcarboxamido)phenyl]acetyl]-(4 S )-methoxy-(2 S )-pyrrolidinylmethoxy]cyclohexanecarboxylic acid} on Ascaris antigen–induced airway inflammation and hyperresponsiveness in a murine asthmatic model. Oral administration of Compound A significantly inhibited eosinophil infiltration into BALF and airway hyperresponsiveness 48 h after the antigen challenge. Histologic analysis of the lung sections confirmed the BALF result and revealed suppression of edema and mucus hyperplasia at 8 and 48 h after the challenge, respectively. These findings clearly show that orally active Compound A has therapeutic potential for treatment of asthma.
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Identification of trans-4-[1-[[7-fluoro-2-(1-methyl-3-indolyl)-6-benzoxazolyl]acetyl]-(4S)-fluoro-(2S)-pyrrolidinylmethoxy]cyclohexanecarboxylic acid as a potent, orally active VLA-4 antagonist.
Bioorganic & medicinal chemistry, 2011Co-Authors: Masaki Setoguchi, Jun Chiba, Gensuke Takayama, Yutaka Iigo, Shin Iimura, Yuuichi Sugimoto, Yoshiyuki Yoneda, Toshiyuki Watanabe, Fumihito Muro, Mika YokoyamaAbstract:For the purpose of obtaining orally potent VLA-4 inhibitors, we have carried out structural modification of the (N'-phenylureido)phenyl group in compound 1, where the group was found to be attributed to poor pharmacokinetic profile in our previous research. Through modification, we have identified several compounds with both potent in vitro activity and improved oral exposure. In particular, compound 7e with 7-fluoro-2-(1-methyl-1H-indol-3-yl)-1,3-benzoxazolyl group as a novel replacement of the (N'-phenylureido)phenyl group significantly inhibited eosinophil infiltration into bronchoalveolar lavage fluid at 15mg/kg in an Ascaris-antigen-induced murine bronchial inflammatory model, and its efficacy was comparable to that of the anti-mouse α(4) antibody (R1-2).
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Identified a morpholinyl-4-piperidinylacetic acid derivative as a potent oral active VLA-4 antagonist
Bioorganic & Medicinal Chemistry Letters, 2005Co-Authors: Jun Chiba, Nobuo Machinaga, Tohru Takashi, Akio Ejima, Gensuke Takayama, Mika Yokoyama, Atsushi Nakayama, John J. Baldwin, Edward Mcdonald, Kurt W. SaionzAbstract:Abstract An investigation into the structure–activity relationship of a lead compound, prolyl-5-aminopentanoic acid 4 , led to the identification of a novel series of 4-piperidinylacetic acid, 1-piperazinylacetic acid, and 4-aminobenzoic acid derivatives as potent VLA-4 antagonists with low nanomolar IC 50 values. A representative compound morpholinyl-4-piperidinylacetic acid derivative ( 13d : IC 50 = 4.4 nM) showed efficacy in the Ascaris -antigen sensitized murine airway inflammation model by oral administration.
Philip J Cooper - One of the best experts on this subject based on the ideXlab platform.
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evidence for in utero sensitization to Ascaris lumbricoides in newborns of mothers with ascariasis
The Journal of Infectious Diseases, 2009Co-Authors: Irene Guadalupe, Philip J Cooper, Martha E Chico, Susana Benitez, Edward Mitre, Thomas B NutmanAbstract:Human infections with Ascaris lumbricoides may have important effects on allergy and susceptibility to infectious diseases that start in early life. To investigate if sensitization to Ascaris occurs in utero, we measured IFN-γ and IL-4 responses in Ascaris antigen-stimulated cord blood of newborns of infected and non-infected mothers using flow cytometry. There was evidence of elevated frequencies of IFN-γ and IL-4-expressing CD4+ T cells in newborns of infected mothers compared to those of non-infected mothers. Our data provide evidence of in utero sensitization to A. lumbricoides, and raise the possibility that the immunological effects of infection start in the fetus.
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repeated treatments with albendazole enhance th2 responses to Ascaris lumbricoides but not to aeroallergens in children from rural communities in the tropics
The Journal of Infectious Diseases, 2008Co-Authors: Philip J Cooper, Martha E Chico, Ana L Moncayo, Irene Guadalupe, Susana Benitez, Maritza Vaca, George E GriffinAbstract:Geohelminth infections are associated with a modulation of immunity to parasite antigens and aeroallergens that may be affected by anthelmintic treatment. To investigate this, we compared cytokine responses between children that had received repeated doses of albendazole over a year or no treatment. Whole blood was cultured with Ascaris antigen and house dust mite and cockroach allergens and IL-5, IL-13, IFN-γ, and IL-10 were measured. Anthelmintic treatment was associated with enhanced production of Th2 cytokines to parasite antigen, but did not affect responses to aeroallergens. The data indicate that long-term treatment may be associated with increased antiparasite Th2 immunity.
Roy Patterson - One of the best experts on this subject based on the ideXlab platform.
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Immunoglobulin E-Mediated Respiratory Responses of Subhuman Primates
The American review of respiratory disease, 2015Co-Authors: Roy Patterson, Catharine H Talbot, Bernard H BoothAbstract:An immunoglobulin E (IgE)-mediated allergic respiratory response was established in rhesus monkeys. This reproducible respiratory reaction occurred in response to bronchial challenge with purified Ascaris antigen. A variety of respiratory reactors and nonreactors was obtained. The bronchial response was partially inhibited by an antihistaminic agent and partially reversed by a beta-adrenergic stimulating agent. A beta-adrenergic blocking agent did not potentiate the IgE-mediated respiratory response. The respiratory response in the most reactive animals was persistent throughout a 17-month period of observation. No differences in sensitivity to histamine in the group of animals with variable respiratory response occurred, and no correlations existed between the degree of respiratory reactivity to methacholine and the response to antigen.
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Sequential Immunologic Stimuli to the Respiratory Tract
The American review of respiratory disease, 2015Co-Authors: Roy Patterson, Kathleen E. Harris, Irena M. SuszkoAbstract:Immunologic stimuli to the airway of rhesus monkeys were given by aerosol challenge with Ascaris antigen or anti-IgE. Both of these stimuli produce immediate-type airway responses. When 2 sequential aerosol challenges were given during the same experiment, the response following the second stimulus was always less than or equal to the first response following any combination of stimuli except the anti-IgE-Ascaris sequence. The second response following the latter challenge was always greater than or equal to the first response. The possibility that this exception was the result of anti-IgE priming mediator releasing cells for antigen was not supported by in vitro experiments. It is suggested that the results obtained with the anti-IgE-Ascaris sequence may relate to the presence of intralumenal mast cells in the bronchi and the molecular weights of the 2 immunologic stimuli.
