Review2019
CRAC channels and disease - From human CRAC channelopathies and animal models to novel drugs
Feske et al.
Cell Calcium
Review of human CRAC channelopathies and animal models that links ORAI/STIM biology to therapeutic development.
00Scientific publications
Research across CRAC channel biology and therapeutic development.
Selected publications on CRAC channel biology, pulmonary hypertension, acute and chronic pancreatitis, and other diseases.
01CRAC channel biology
CRAC channel biology and drug discovery
Foundational discoveries and reviews defining STIM1/Orai1-mediated store-operated calcium entry and the therapeutic rationale for CRAC channel inhibition.
Selected publications
Review2018
CRAC channels as targets for drug discovery and development
Stauderman
Cell Calcium
Review of CRAC channel pharmacology, small-molecule discovery, and the progression of CRAC inhibitors into clinical development.
Preclinical2013
Blockade of NOX2 and STIM1 signaling limits lipopolysaccharide-induced vascular inflammation
Gandhirajan et al.
Journal of Clinical Investigation
Preclinical study linking STIM1-dependent calcium entry to endothelial activation, vascular permeability, and inflammatory lung injury.
Discovery2006
Genome-wide RNAi screen of Ca2+ influx identifies genes that regulate Ca2+ release-activated Ca2+ channel activity
Zhang et al.
Proceedings of the National Academy of Sciences
Genome-wide RNAi screen that identified Orai1 as an essential component of CRAC channel activity.
Discovery2006
A mutation in Orai1 causes immune deficiency by abrogating CRAC channel function
Feske et al.
Nature
Human genetics study establishing that loss of ORAI1 function can abolish CRAC channel activity and cause severe immunodeficiency.
Discovery2005
STIM1 is a Ca2+ sensor that activates CRAC channels and migrates from the Ca2+ store to the plasma membrane
Zhang et al.
Nature
Foundational study establishing STIM1 as the endoplasmic-reticulum calcium sensor that activates CRAC channels.
Discovery2005
STIM1, an essential and conserved component of store-operated Ca2+ channel function
Roos et al.
Journal of Cell Biology
RNAi-based discovery study establishing STIM1 as an essential and conserved component of store-operated calcium entry.
02Pulmonary hypertension
Pulmonary hypertension and cardiac biology
Preclinical, translational, and review articles evaluating Orai1/CRAC channel signaling in pulmonary vascular disease and ventricular remodeling.
Selected publications
Preclinical2025
Combination of Orai1 inhibitor CM5480 with specific therapy mitigates pulmonary hypertension and its cardiac dysfunction
Saint-Martin Willer et al.
JCI Insight
Preclinical study evaluating CM5480 alone and with standard PAH therapies across pulmonary vascular and right-ventricular endpoints.
Preclinical2025
Ca2+ cycling alteration in a porcine model of right ventricular dysfunction
Antigny et al.
Circulation: Heart Failure
Large-animal CTEPH study characterizing calcium-cycling abnormalities and STIM1L/Orai1 remodeling in right-ventricular dysfunction.
Review2024
Orai1/STIMs modulators in pulmonary vascular diseases
Saint-Martin Willer et al.
Cell Calcium
Review of Orai1/STIM regulation in pulmonary circulation, inflammation, and cardiorespiratory disease.
Preclinical2022
Orai1 inhibitors as potential treatments for pulmonary arterial hypertension
Masson et al.
Circulation Research
Target-validation study showing increased Orai1 expression and activity in human PAH vascular cells and effects of Orai1 inhibition across experimental PH models.
Review2022
The SOCE machinery: an unbalanced knowledge between left and right ventricular pathophysiology
Sabourin et al.
Cells
Review comparing store-operated calcium-entry biology in left- and right-ventricular pathophysiology and highlighting gaps in RV research.
Preclinical2020
Orai1 channel inhibition preserves left ventricular systolic function and normal Ca2+ handling after pressure overload
Bartoli et al.
Circulation
Pressure-overload study showing that Orai1 inhibition preserved left-ventricular systolic function and reduced adverse remodeling.
Preclinical2018
Ca2+ handling remodeling and STIM1L/Orai1/TRPC1/TRPC4 upregulation in monocrotaline-induced right ventricular hypertrophy
Sabourin et al.
Journal of Molecular and Cellular Cardiology
MCT model study identifying altered calcium handling and STIM1L/Orai1/TRPC upregulation in right-ventricular hypertrophy.
Review2018
ORAI channels as potential therapeutic targets in pulmonary hypertension
Rode et al.
Physiology
Review of ORAI channel involvement in pulmonary vasoconstriction, vascular remodeling, inflammation, and thrombosis.
Preclinical2011
Critical role for stromal interaction molecule 1 in cardiac hypertrophy
Hulot et al.
Circulation
Preclinical study establishing STIM1-dependent store-operated calcium entry as a driver of cardiac hypertrophy.
03Pancreatitis
Acute and chronic pancreatitis
Clinical and preclinical studies of calcium signaling, CRAC channel inhibition, and biomarkers in pancreatic disease.
Selected publications
Clinical analysis2026
Lactate Dehydrogenase, Interleukin-6, and 24 h Intra-Abdominal Pressure Exhibit Early Predictive Value in Hypertriglyceridemic Pancreatitis Complicated by Acute Respiratory Distress Syndrome
Zhu et al.
Emergency Medicine International
Independent retrospective study of 111 ICU patients with hypertriglyceridemic acute pancreatitis, evaluating LDH and other predictors of ARDS.
Clinical trial2026
Zegocractin for acute pancreatitis with systemic inflammatory response syndrome: a randomized, controlled, dose-ranging, phase 2b trial
Sutton et al.
EClinicalMedicine
Randomized, placebo-controlled Phase 2b trial of zegocractin in 216 patients with acute pancreatitis and SIRS.
Preclinical2023
Orai1 calcium channel inhibition prevents progression of chronic pancreatitis
Szabo et al.
JCI Insight
Preclinical study showing that CM5480 protected pancreatic acinar and ductal function and reduced inflammatory and fibrotic progression in chronic pancreatitis models.
Preclinical2022
Bile acid- and ethanol-mediated activation of Orai1 damages pancreatic ductal secretion in acute pancreatitis
Pallagi et al.
The Journal of Physiology
Preclinical study showing that Orai1-mediated calcium entry impairs pancreatic ductal secretion and that selective inhibition protects ductal function.
Commentary2022
CRAC channel inhibitors in pancreatic pathologies
Gerasimenko & Gerasimenko
The Journal of Physiology
Commentary on Orai1-mediated pancreatic injury and the therapeutic rationale for CRAC channel inhibition in pancreatic disease.
Clinical trial2021
Auxora for the treatment of patients with acute pancreatitis and accompanying systemic inflammatory response syndrome: clinical development of a calcium release-activated calcium channel inhibitor
Bruen et al.
Pancreas
Phase 2 study evaluating intravenous Auxora in patients with acute pancreatitis and SIRS, including clinical recovery and safety outcomes.
Preclinical2019
The Orai Ca2+ channel inhibitor CM4620 targets both parenchymal and immune cells to reduce inflammation in experimental acute pancreatitis
Waldron et al.
The Journal of Physiology
Preclinical study showing that CM4620 acted on pancreatic parenchymal and immune cells to reduce inflammation and disease severity.
Preclinical2015
Inhibitors of ORAI1 prevent cytosolic calcium-associated injury of human pancreatic acinar cells and acute pancreatitis in 3 mouse models
Wen et al.
Gastroenterology
Foundational study in human pancreatic acinar cells and three mouse models showing that ORAI1 inhibition reduced calcium overload, cell injury, and pancreatitis severity.
04Other indications
Other indications and translational research
Clinical and preclinical research evaluating CRAC channel biology across acute lung injury, inflammatory disease, kidney injury, and neurologic disease.
Selected publications
Translational2026
The CRAC channel inhibitor Auxora reprograms pathogenic alveolar macrophage–T cell circuits in viral pneumonia
Casalino-Matsuda et al.
Journal of Clinical Investigation
Research letter evaluating Auxora's effects on pathogenic alveolar macrophage–T cell signaling in viral pneumonia.
Clinical analysis2025
Reduction in D-dimer levels after treatment with Auxora in patients with severe COVID-19 pneumonia
Hou et al.
Thrombosis Update
Biomarker analysis from CARDEA evaluating Auxora-associated changes in D-dimer, angiopoietins, and sCD25 in severe COVID-19 pneumonia.
Clinical trial2022
Auxora vs. placebo for the treatment of patients with severe COVID-19 pneumonia: a randomized-controlled clinical trial
Bruen et al.
Critical Care
Randomized, double-blind, placebo-controlled Phase 2 CARDEA trial of Auxora in patients with severe COVID-19 pneumonia.
Translational2022
Store-operated calcium entry controls innate and adaptive immune cell function in inflammatory bowel disease
Letizia et al.
EMBO Molecular Medicine
Human translational and preclinical study showing that CRAC channel inhibition modulated inflammatory immune-cell function in inflammatory bowel disease.
Preclinical2022
Distinct roles of ORAI1 in T cell-mediated allergic airway inflammation and immunity to influenza A virus infection
Wang et al.
Science Advances
Preclinical study defining distinct roles of ORAI1 in T-cell-driven allergic airway inflammation and antiviral immunity.
Preclinical2021
Microglial calcium waves during the hyperacute phase of ischemic stroke
Liu et al.
Stroke
In vivo imaging study identifying CRAC-mediated microglial calcium waves during the hyperacute phase of ischemic stroke.
Clinical trial2020
Auxora versus standard of care for the treatment of severe or critical COVID-19 pneumonia: results from a randomized controlled trial
Miller et al.
Critical Care
Early randomized controlled study evaluating Auxora plus standard of care in severe or critical COVID-19 pneumonia.
Preclinical2019
Calcium channel Orai1 promotes lymphocyte IL-17 expression and progressive kidney injury
Mehrotra et al.
Journal of Clinical Investigation
Preclinical and translational study linking Orai1-dependent Th17 responses to progressive kidney injury after acute kidney injury.
Preclinical2019
Microglial calcium release-activated calcium channel inhibition improves outcome from experimental traumatic brain injury and microglia-induced neuronal death
Mizuma et al.
Journal of Neurotrauma
Preclinical study showing that microglial CRAC channel inhibition reduced neuronal injury and improved outcomes after experimental traumatic brain injury.