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Chemical Structure| 1654725-02-6 Chemical Structure| 1654725-02-6

Structure of GLPG1837
CAS No.: 1654725-02-6

Chemical Structure| 1654725-02-6

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GLPG-1837 is a cystic fibrosis transmembrane conductance regulator (CFTR) potentiator1, shows enhanced efficacy on CFTR mutants harboring Class III mutations compared to Ivacaftor.

Synonyms: ABBV-974

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Product Details of GLPG1837

CAS No. :1654725-02-6
Formula : C16H20N4O3S
M.W : 348.42
SMILES Code : O=C(C1=NNC=C1)NC(S2)=C(C(N)=O)C3=C2C(C)(C)OC(C)(C)C3
Synonyms :
ABBV-974
MDL No. :MFCD31630754
InChI Key :GHTGYZMBQPXTCQ-UHFFFAOYSA-N
Pubchem ID :117857370

Safety of GLPG1837

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Isoform Comparison

Biological Activity

In Vitro:

Cell Line
Concentration Treated Time Description References
HEK293 cells 20 μM Evaluate the effect of SR9009 on a luciferase reporter driven by the Bmal1 promoter PMC8087279
16HBE14o2 cells 10 μM 72 hours To evaluate the effect of GLPG1837 on CFTR activity, results showed that GLPG1837 significantly increased CFTR function in 16HBE14o2 cells. PMC8086047
FRT-G542X cells 3 nM to 10 μM 48 hours To evaluate the effect of GLPG1837 on CFTR activity, results showed that GLPG1837 activated CFTR in FRT-G542X cells, although it was less active than ivacaftor for this mutant. PMC8086047
FRT-R1162X cells 3 nM to 10 μM 48 hours To evaluate the effect of GLPG1837 on CFTR activity, results showed that GLPG1837 elicited dose-dependent increases in CFTR activity that exceeded those from ivacaftor in FRT-R1162X cells. PMC8086047
FRT-W1282X cells 3 nM to 10 μM 48 hours To evaluate the effect of GLPG1837 on CFTR activity, results showed that GLPG1837 elicited dose-dependent increases in CFTR activity that exceeded those from ivacaftor in FRT-W1282X cells. PMC8086047
Intestinal organoids 3 μM acute treatment To assess the potentiating effect of GLPG1837 on R352Q/F508del CFTR function, results showed GLPG1837 significantly increased FIS (AUC increased by 910.6). PMC9273222
Human nasal epithelial cells (hNECs) 10 μM acute treatment To assess the potentiating effect of GLPG1837 on R352Q/F508del CFTR function, results showed GLPG1837 significantly increased CFTR activity by twofold, reaching 23.5 μA/cm2 above baseline. PMC9273222
FRT cells 20 μM Tested the effect of GLPG1837 on I1234del-CFTR activation, showing that GLPG1837 combined with ASP-11 increased current. PMC7854863
CHO cells 20.0 μM Evaluation of GW627368X antagonism at human prostanoid CRTH2, EP1, EP2, EP3, FP, and IP receptors, showing no significant antagonism at CRTH2, EP2, EP3, IP, and FP receptors. PMC7008954
HEK293 cells 103.5 nM 24 hours Evaluate the effect of SR9009 on a luciferase reporter driven by the Bmal1 promoter PMC6212544
CFBe41o- cells 3.5 nM 24 hours Evaluate the potentiation effect of GLPG1837 on low temperature rescued F508del CFTR PMC6212544
CHO cells 20 μM Evaluation of GW627368X antagonism at human prostanoid CRTH2, EP1, EP2, EP3, FP, and IP receptors, showing no significant antagonism at CRTH2, EP2, EP3, IP, and FP receptors. PMC8087279

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
Rat Sprague-Dawley rats Intravenous and oral 0.1 mg/kg (IV), 5 mg/kg (PO) Single dose Evaluate the pharmacokinetic properties of GLPG1837 PMC11017246

Clinical Trial:

NCT Number Conditions Phases Recruitment Completion Date Locations
NCT02325037 Healthy Phase 1 Completed - Belgium ... More >> SGS LSS Clinical Pharmacology Unit Antwerp Antwerp, Belgium Less <<
NCT02562950 Healthy Phase 1 Completed - Belgium ... More >> SGS LSS Clinical Pharmacology Unit Antwerp Antwerp, Belgium Less <<
NCT02707562 Cystic Fibrosis Phase 2 Completed - Australia ... More >> Royal Adelaide Hospital Adelaide, Australia The Prince Charles Hospital Chermside, Australia Monash Medical Centre Clayton, Australia Sir Charles Gairdner Hospital Nedlands, Australia Mater Adult Hospital South Brisbane, Australia Czech Republic Fakultni nemocnice v Motole Praha 5, Czech Republic Germany Charité Universitätsmedizin Berlin Berlin, Germany Universitätsklinkikum Koeln Cologne, Germany Uniklinik Carl-Gustav-Carus Dresden, Germany Lungenheilkunde München-Pasing München, Germany Ireland Beamont Hospital Dublin, Ireland St. Vincent's University Hospital Dublin, Ireland United Kingdom Queen Elizabeth University Hospital Glasgow, United Kingdom Liverpool Heart and Chest Hospital Liverpool, United Kingdom Royal Brompton Hospital London, United Kingdom The Medicines Evaluation Unit Ltd Manchester, United Kingdom Less <<
NCT02690519 Cystic Fibrosis Phase 2 Completed - Belgium ... More >> University Hospital Antwerp Antwerp, Belgium University Hospital Ghent Ghent, Belgium University Hospitals Leuven Leuven, Belgium Netherlands AMC Amsterdam, Netherlands UMC Utrecht Utrecht, Netherlands Less <<
NCT02562859 Healthy Phase 1 Completed - Belgium ... More >> SGS LSS Clinical Pharmacology Unit Antwerp Antwerp, Belgium Less <<

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

2.87mL

0.57mL

0.29mL

14.35mL

2.87mL

1.44mL

28.70mL

5.74mL

2.87mL

References

 

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