title: Improvement of pulmonary function by oral treatment with a VLA-4 antagonist in a mouse asthmatic model.
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]-(4S)methoxy-(2S)-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.
authors: Daiichi Sankyo Co., Ltd., Tokyo, Japan. takayama.gensuke.ib@daiichisankyo.co.jp
authors: Gensuke
authors: G
authors: Takayama
authors: Keiko
authors: K
authors: Matsumoto
authors: Tomoe
authors: T
authors: Taira
authors: Misato
authors: M
authors: Aonuma
authors: Mika
authors: M
authors: Yokoyama
authors: Yutaka
authors: Y
authors: Iigo
authors: Tohru
authors: T
authors: Takashi
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000284:Administration, Oral; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D003509:Cyclohexanecarboxylic Acids / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004487:Edema / Q000188:drug therapy; D004804:Eosinophils / Q000187:drug effects; D005260:Female; D007249:Inflammation / Q000188:drug therapy; D039041:Integrin alpha4beta1 / Q000037:antagonists & inhibitors*; D008168:Lung / Q000187:drug effects* / Q000502:physiology* / Q000503:physiopathology; D051379:Mice; D011759:Pyrrolidines / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D012137:Respiratory System / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D013997:Time Factors
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D003509:Cyclohexanecarboxylic Acids; D039041:Integrin alpha4beta1; D011759:Pyrrolidines; C576301:trans-4-(1-((2,5-dichloro-4-(1-methyl-3-indolylcarboxyamide)phenyl)acetyl)-(4S)-methoxy-(2S)-pyrrolidinylmethoxy)cyclohexanecarboxylic acid; D000109:Acetylcholine