22 // THE NEW GASTROENTEROLOGIST: INSIGHTS FOR FELLOWS & YOUNG GIS SUMMER 2016
SNAPSHOTS FROM THE
Snapshots from the AGA Journals
Dr. Wayne I. Lencer, AGAF, is chief of the division of gastroenterol-
ogy, hepatology and nutrition and the Harry Schwachman Chair in
Pediatric Gastroenterology at Boston Children’s Hospital; and Long-
wood Professor of Pediatrics at Harvard Medical School, Boston.
He has no conflicts of interest.
The article by Cil et al. de- scribes the discovery and characterization of a small molecule (termed CF- TRact-J027), which is capable of opening the Cl- channel
CFTR [the cystic fibrosis transmem-brane regulator]. The paper shows
that CFTRact-J027 induces intestinal
Cl secretion in the mouse by opening
CFTR, and the authors suggest that
the molecule may have clinical applications for the treatment of constipation in humans.
CFTRact-J027 has several potential
advantages, compared with other small
molecules, in use for the treatment of
constipation, including greater appar-
ent potency and the chance for local
such as constipation-predominant irritable bowel syndrome and opioid-in-duced constipation affect a large and
growing proportion of the U.S. population. The discovery of CFTRact-J027
is an important and timely advance
toward increasing the therapeutic
options for these disorders. There are
still many hurdles to overcome before
clinical application, but perhaps CFTRact-J027, or another more refined
compound that opens CFTR, will be
found effective in treating constipation
in humans. This would have a big impact. n
Key clinical point: Treatment at
the nanomolecular level may become an alternative for various
types of constipation.
Major finding: Oral doses of CF-
TRact-J027 normalized stool output
and water content in a lopera-mide-induced mouse model of constipation with a 50% effective dose
of approximately 0.5 mg/kg.
Data source: A proof-of-concept
study in which a cell-based screen
was performed for 120,000 drug-like, synthetic small molecules that
were then tested in constipation-in-duced mice and control mice.
Disclosures: Dr. Cil and two coauthors are inventors on a provisional
patent filing, with rights owned by
the University of California, San
Francisco. The study was funded
in part by several grants from organizations including the National
Institutes of Health and the Cystic
Cell-based Strategy Curbs Constipation
May Cellular and Molecular Gastroenterology and Hepatology (doi: 10.1016/j.jcmgh.2015.12.010)