ArticleMolecular pharmacology2010
Crofelemer, an antisecretory antidiarrheal proanthocyanidin oligomer extracted from Croton lechleri, targets two distinct intestinal chloride channels.
Article in Molecular pharmacology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 5 registered trials, which are not on this map. Cited by 64 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
An Open Label Study to Characterize the Incidence and Severity of Diarrhea in Patients With HER2+ Breast Cancer Treated With Neratinib With or Without Trastuzumab
A Phase 4 Open Label Study to Assess the Safety and Effects of Crofelemer on the Gut Microbiome in Healthy Volunteers and in People Living With HIV/AIDS (PLWHA) With Non-Infectious Diarrhea
A Phase 3 Multicenter, Randomized, Double-blind Placebo-controlled Trial Evaluating Crofelemer for the Prophylaxis of Diarrhea in Adult Patients With Solid Tumors Receiving Targeted-cancer Therapies With or Without Standard Chemotherapy
Evaluation of Safety, Tolerability and Efficacy of Crofelemer Following Multiple Ascending Doses of Crofelemer Powder for Oral Solution in Pediatric Participants With Microvillus Inclusion Disease (MVID)
A Phase 2, Placebo-Controlled, Randomized, Double-Blind Study of 2 Doses of Crofelemer for the Treatment of Adult Patients With Short Bowel Syndrome and Intestinal Failure (SBS-IF) Without Colon-in-continuity (CIC)
Who cites it
64 citing papers in PubMed, 134 citations in OpenAlex.
- HALT-D: a randomized open-label phase II study of crofelemer for the prevention of chemotherapy-induced diarrhea in patients with HER2-positive breast cancer receiving trastuzumab, pertuzumab, and a taxane.Breast cancer research and treatment · 2022Trial
- Prophylactic use of a standardized botanical extract for the prevention of naturally occurring diarrhea in newborn Holstein calves.Journal of dairy science · 2017Trial
- BEST4⁺ cells: a potential hub of intestinal ion transport and diarrhea manipulation.Advanced biotechnology · 2026Review
- Epithelial plasma membrane transporters as drug targets.Physiological reviews · 2026Review
- Krisanaklan Reduces Intestinal Anion and Fluid Secretion Through Inhibition of NaAnnals of the New York Academy of Sciences · 2026Article
- From forgotten to frontier: vindicating Latin America's indigenous biotechnology.Journal of ethnobiology and ethnomedicine · 2025Review
- DTIAM: a unified framework for predicting drug-target interactions, binding affinities and drug mechanisms.Nature communications · 2025Article
- ANO1: central role and clinical significance in non-neoplastic and neoplastic diseases.Frontiers in immunology · 2025Review
- Review
- Article
- Effects of orally administered crofelemer on the incidence and severity of neratinib-induced diarrhea in female dogs.PloS one · 2024Article
- Patient-derived enteroids provide a platform for the development of therapeutic approaches in microvillus inclusion disease.The Journal of clinical investigation · 2023Article
- Rare variants in ANO1, encoding a calcium-activated chloride channel, predispose to moyamoya disease.Brain : a journal of neurology · 2023Article
- Therapy Development for Microvillus Inclusion Disease using Patient-derived Enteroids.bioRxiv : the preprint server for biology · 2023Article
- The Roots ofMolecules (Basel, Switzerland) · 2023Article
- Intestinal secretory mechanisms and diarrhea.American journal of physiology. Gastrointestinal and liver physiology · 2022Review
- Paneth Cell Secretion in vivo Requires Expression of Tmem16a and Tmem16f.Gastro hep advances · 2022Article
- Emerging Modulators of TMEM16A and Their Therapeutic Potential.The Journal of membrane biology · 2021Review
- Natural Phytochemicals Derived from Gymnosperms in the Prevention and Treatment of Cancers.International journal of molecular sciences · 2021Review
- Improved Control of Tyrosine Kinase Inhibitor-Induced Diarrhea with a Novel Chloride Channel Modulator: A Case Report.Oncology and therapy · 2021Article
4 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Crofelemer, a purified proanthocyanidin oligomer extracted from the bark latex of Croton lechleri, is in clinical trials for secretory diarrheas of various etiologies. We investigated the antisecretory mechanism of crofelemer by determining its effect on the major apical membrane transport and signaling processes involved in intestinal fluid transport. Using cell lines and measurement procedures to isolate the effects on individual membrane transport proteins, crofelemer at 50 microM had little or no effect on the activity of epithelial Na(+) or K(+) channels or on cAMP or calcium signaling. Crofelemer inhibited the cystic fibrosis transmembrane regulator (CFTR) Cl(-) channel with maximum inhibition of approximately 60% and an IC(50) approximately 7 microM. Crofelemer action at an extracellular site on CFTR produced voltage-independent block with stabilization of the channel closed state. Crofelemer did not affect the potency of glycine hydrazide or thiazolidinone CFTR inhibitors. Crofelemer action resisted washout, with <50% reversal of CFTR inhibition after 4 h. Crofelemer was also found to strongly inhibit the intestinal calcium-activated Cl(-) channel TMEM16A by a voltage-independent inhibition mechanism with maximum inhibition >90% and IC(50) approximately 6.5 microM. The dual inhibitory action of crofelemer on two structurally unrelated prosecretory intestinal Cl(-) channels may account for its intestinal antisecretory activity.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.