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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 103.5 nM 24 hours Evaluate the potentiation effect of GLPG1837 on WT CFTR Front Pharmacol. 2018 Oct 26;9:1221.
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. Am J Respir Cell Mol Biol. 2021 May;64(5):604-616.
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. Am J Respir Cell Mol Biol. 2021 May;64(5):604-616.
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. Am J Respir Cell Mol Biol. 2021 May;64(5):604-616.
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. Am J Respir Cell Mol Biol. 2021 May;64(5):604-616.
FRT cells 20 μM Tested the effect of GLPG1837 on I1234del-CFTR activation, showing that GLPG1837 combined with ASP-11 increased current. J Cyst Fibros. 2021 May;20(3):452-459.
CHO cells 20.0 μM To assess the effect of GLPG1837 on N1303K-CFTR channel activity, results showed that 20.0 μM GLPG1837 increased N1303K-CFTR currents by approximately 17-fold. J Cyst Fibros. 2018 Sep;17(5):573-581.
CFBe41o- cells 3.5 nM 24 hours Evaluate the potentiation effect of GLPG1837 on low temperature rescued F508del CFTR Front Pharmacol. 2018 Oct 26;9:1221.
HEK293 cells 20 μM GLPG1837 enhanced the currents of E60X- and G542X-CFTR, suggesting these channels are likely full-length proteins J Physiol. 2020 Feb;598(3):517-541.
CHO cells 20 μM GLPG1837 significantly increased the current of W1282X-CFTR, indicating the open probability (Po) of the channel is extremely low J Physiol. 2020 Feb;598(3):517-541.

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 J Med Chem. 2024 Apr 11;67(7):5216-5232

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

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