Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0022104 (
irritable bowel syndrome
)
8,033
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
The identification of orally active, small molecule antagonists of the alpha4beta1 integrin,
VLA-4
, could lead to therapeutic agents with utility in a number of clinical settings, including asthma, multiple sclerosis and
IBD
. Starting from CDR3 sequences conserved among neutralizing alpha4 antibodies, peptides were identified that antagonized
VLA-4
mediated adhesion in vitro. Through a series of structural modifications, these peptides evolved into small molecules that exhibited high potency and selectivity for
VLA-4
in cell adhesion assays. Finally, through the optimization of physical and pharmacokinetic properties, compounds were identified that exhibited oral activity in animal models of asthma and multiple sclerosis.
...
PMID:The identification and optimization of orally efficacious, small molecule VLA-4 antagonists. 1554 38
