Synonyms: ABBV/GLPG-3221 | compound 19 [PMID: 31749908]
Compound class:
Synthetic organic
Comment: ABBV-3221(GLPG-3221) is a novel cystic fibrosis transmembrane conductance regulator (CFTR) corrector that is being developed in a collaboration between AbbVie and Galapagos for the treatment of cystic fibrosis [2]. It was designed to provide improved clinical efficacy when used in a triple combination with a CFTR potentiator and a second, but mechanistically distinct, corrector molecule. ABBV-3221 enhances channel activity by increasing pore opening whilst the channel's two nucleotide-binding domains are dimerized [1].
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Bioactivity Comments |
In vitro (in cells with the homozygous F508delCFTR mutation from a CF donor), addition of ABBV-3221 (corrector 2; C2) to the combination of ABBV-2222 (corrector 1; C1, with a similar mechanism to lumacaftor) and GLPG1837 (potentiator) increased the CFTR current with an EC50 of 105 nM, and increased the maximum response by almost six-fold, compared to the double ABBV-2222/GLPG1837 combination [2]. |
Selectivity at ion channels | ||||||||||||||||||||||||||||||||||
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