CFTR/cystic fibrosis transmembrane conductance regulator
Cystic fibrosis transmembrane conductance regulator (CFTR) - corrector (type 1, C1); EC50 = 27 nM (pEC50 = 7.56 ± 0.16, n=19) in CFBE41o- F508del CFTR-HRP cell surface expression assay; EC50 = 20.8 ± 2.7 nM (n=6) in CFBE-DG3 TECC functional assay; EC50 = 2.85 ± 0.4 nM (n=5 donors) in primary HBE TECC functional assay (F508del/F508del); potency range 1.6 to 13.1 nM across 16 different F508del/F508del homozygous donor cells (median ~6 nM). [2]

Galicaftor (ABBV-2222; GLPG-2222)has an EC50 <10 nM and strong in vitro functional activity in primary patient cells expressing F508del/F508del CFTR[2].
ABBV-2222 Promotes Maturation of F508delCFTR as Assessed by Western Blot. ABBV-2222 Stabilizes the Nucleotide Binding Domain 1/Membrane-Spanning Domain Interface. ABBV-2222 Corrects F508delCFTR through Action on Membrane-Spanning Domain 1. [2]

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Compound 22 [Galicaftor (ABBV-2222; GLPG-2222)] was highly potent (5 nM) and efficacious in cells from multiple CF patient donors who have F508del homozygous mutation. In comparison with Lumacaftor, 22 was significantly more potent (>25-fold) and exhibited comparable efficacy. It demonstrated low clearance across multiple preclinical species, did not inhibit CYP enzymes, was not a CYP3A4 inducer, and therefore presented a low DDI perpetrator liability[1].

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ABBV-2222 in CFBE41o- F508del CFTR-HRP cell surface expression assay: EC50 = 27 nM (pEC50 = 7.56 ± 0.16, n=19); relative efficacy = 141 ± 15% normalized to compound 15; approximately 10-fold more potent than lumacaftor (EC50 = 251 nM, pEC50 = 6.6 ± 0.08, n=3) and ~20-fold more potent than tezacaftor (EC50 = 586 nM, pEC50 = 6.23 ± 0.05, n=6); efficacy drop-off observed above 2.22 μM. [2]
ABBV-2222 promoted maturation of F508delCFTR as measured by accumulation of higher molecular weight glycosylated band C by Western blot in CFBE cells; concentration-dependent increase in band C/B ratio. [2]
ABBV-2222 in CFBE-DG3 TECC functional assay: EC50 = 20.8 ± 2.7 nM (n=6); tezacaftor was ~14-fold less potent (EC50 = 266.9 ± 38.6 nM). [2]
ABBV-2222 in primary HBE TECC functional assay (F508del/F508del): EC50 = 2.85 ± 0.4 nM (n=5 donors); lumacaftor EC50 = 122.8 ± 13.8 nM (n=1 donor); tezacaftor EC50 = 148.2 ± 25.7 nM (n=4 donors); ABBV-2222 exhibited equivalent efficacy to lumacaftor and ~20% improvement in efficacy compared with tezacaftor. [2]
ABBV-2222 HBE TECC potencies ranged from 1.6 to 13.1 nM across 16 different F508del/F508del homozygous donor cells (median ~6 nM). [2]
Enantiomer A-9433 was ~160-fold less potent and ~70% less efficacious than ABBV-2222. [2]
ABBV-2222 showed no functional additivity with lumacaftor or tezacaftor in HBE TECC assay, suggesting similar mechanism of action. [2]
No difference in potency of ABBV-2222 with acute vs. chronic addition of potentiator GLPG1837 (EC50 7.9 vs. 7.3 nM; and 6.4 vs. 5.4 nM respectively). [2]
Onset of F508delCFTR activity showed rapid onset with maximal effect achieved within 12 hours of treatment, sustained up to 96 hours in TECC system. [2]
Patch-clamp experiments: ABBV-2222-treated F508delCFTR had Po = 0.04 (similar to vehicle-treated control); addition of GLPG1837 increased Po to 0.57. [2]
ABBV-2222 substantially rescued folding of F508delCFTR-R1S suppressor mutant and had lesser impact on F508delCFTR-R1070W, indicating preferential impact on NBD1/MSD2 interface restoration (type C1 corrector). [2]
ABBV-2222 increased stabilization of CFTR 375 fragment (containing only MSD1); increased half-life of CFTR 380 fragment; unable to increase accumulation of CFTR 370, suggesting it does not act as a proteasome inhibitor. [2]
ABBV-2222 was selective for F508delCFTR and unable to process mutant hERG (G601S) or mutant PgP (G268V). [2]

Galicaftor (ABBV-2222; GLPG-2222; 1 mg/kg, iv; 1 mg/kg, po) is used in the rat pharmacokinetic experiments to demonstrate its pharmacokinetic characteristics. T1/2 is equal to 2.7 hours (iv). Additionally, the bioavailability (%F) for intragastric injection is 74%[1].
In the CSE-HRP assay using CFBE41o- F508del CFTR-HRP cells, ABBV-2222 (compound 22) showed an EC50 of 5 nM (geometric mean) in cells from multiple CF patient donors with F508del homozygous mutation. It was >25-fold more potent than Lumacaftor and exhibited comparable efficacy. [1]
In the HBE-TECC functional assay using primary human bronchial epithelial cells from F508del/F508del CFTR patients, ABBV-2222 (compound 22) demonstrated an EC50 of 5 nM (Table 6) and 87% maximum activity relative to the positive control compound 15. [1]
The intermediate compound 13 (precursor to ABBV-2222) showed CSE-HRP EC50 of 0.13 µM with 123% max activity and HBE-TECC EC50 of 0.028 µM with 117% max activity. [1]
Compound 21 (7-OCH3 para-carboxylic acid analog) showed HBE-TECC EC50 of 9 nM with 94% max activity. [1]
Compound 20 (7-OCHF2 meta-carboxylic acid analog without para-COOH) showed HBE-TECC EC50 of 75 nM with 117% max activity. [1]
ABBV-2222 (compound 22) demonstrated low hepatocyte clearance: human 7 L/h/kg, rat 6 L/h/kg (Table 6). [1]
ABBV-2222 (compound 22) did not inhibit CYP enzymes and was not a CYP3A4 inducer (CYP3A4 induction at 10 µM was 6.4% of rifampin control, Table 6). [1]
ABBV-2222 is primarily cleared via glucuronidation in human plasma, presenting a low DDI victim liability. [1]

Patch-Clamp Electrophysiological Assay.[2]
To examine the open probability (Po) of F508delCFTR after pretreatment with Galicaftor (ABBV-2222; GLPG-2222), CHO cells transiently transfected with CFTR-cDNA [pcDNA 3.1 Zeo (+) vector; Invitrogen] and GFP encoding pEGFP-C3 were incubated with Galicaftor (ABBV-2222; GLPG-2222) overnight before patch-clamp experiments. To avoid repetition, detailed experimental methods, materials, and data analysis can be found in our latest publication (Yeh et al., 2019).

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Trans-epithelial Current Clamp on Human Bronchial Epithelial Cells Conductance Assay[1]
A cell based assay using the primary human bronchial epithelial cells (hBE) was used as a secondary assay to test novel F508del CFTR correctors for their activity on primary hBE cells with F508del/F508del CFTR mutation. Primary human bronchial epithelial (hBE) cells from F508del/F508del CFTR patients were expanded from 1 × 106 to 250 × 106 cells. For this purpose, cells isolated from CF patients with the homozygous mutation were seeded onto 24 well Corning filter plates that were coated with 3T3 conditioned media and grown at an air–liquid interface for 35 days using an Ultroser G supplemented differentiation media. Apical surface mucus was removed 72 h before the experiment by incubating the apical surface of the cells for 30 min with 3 mM dithiothreitol (DTT) prepared in the differentiation media, followed by aspiration of the mucus along with the media. The apical surface is washed again with phosphate buffered saline (PBS) incubated for 30 min followed with aspiration. The cells were then incubated with the desired dose of the corrector compounds 18–24 h at 37 °C, 5% CO2. The corrector compounds were prepared as 10 mM stocks, and the desired concentrations were prepared in differentiation media and were always applied on the basolateral side of the epithelial cells.

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CYP3A4 Induction: [1]
Cryopreserved primary human hepatocytes were thawed and cultured overnight prior to treatment. Cultured hepatocytes were treated with either test compounds (10 µM), vehicle control (0.1% v/v DMSO), or prototypical inducer of CYP3A4 (rifampin 10 µM) for 48 hours, with culture medium being refreshed every 24 hours. Following the 48 hour treatment, CYP3A4 mRNA levels measured in compound treated hepatocytes were expressed as a percentage of the response of positive control (Rifampin 10 µM). In test compound treated hepatocytes, CYP3A4 mRNA level increase by less than 20% of the response of positive control (Rifampin) is considered low risk for CYP3A4 induction.

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In rat pharmacokinetic studies, ABBV-2222 (compound 22) showed: IV dose 1 mg/kg, clearance 0.55 L/h/kg, half-life 2.7 h; oral dose 2 mg/kg, bioavailability 74% (Table 7). [1]
In dog pharmacokinetic studies, ABBV-2222 (compound 22) showed: IV dose 2 mg/kg, clearance 0.83 L/h/kg, half-life 5.0 h; oral dose 5 mg/kg, bioavailability 40% (Table 7). [1]
ABBV-2222 (compound 22) demonstrated low clearance across multiple preclinical species. [1]

Western Blot Analysis of F508delCFTR Band C/B in Baby Hamster Kidney Cells Expressing Suppressor Mutations.[2]
Briefly, the BHK suppressor mutant cells were seeded at 1 × 106 cells per well onto six-well dishes overnight and then treated with either 0.2% DMSO or 1 µM Galicaftor (ABBV-2222; GLPG-2222) for 18–24 hours at 37°C in a 5% CO2 humidified incubator. Just prior to lysis, cell monolayers were rinsed twice with cold PBS to remove serum and medium.

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Cell Surface Expression-Horse Radish Peroxidase (CSE-HRP) Assay[1]
A cellular assay for measuring the F508del CFTR cell surface expression after correction with test compounds was developed in the human lung derived epithelial cell line (CFBE41o-). This was achieved by expressing the F508del CFTR mutation along with a horseradish peroxidase (HRP) in the fourth exofacial loop and then measuring the HRP activity using luminescence readout from these cells, CFBE41o-F508del CFTR-HRP, that were incubated overnight with the test corrector compounds. Briefly, for this primary assay, the CFBE41o-F508del CFTR-HRP cells were plated in 384-well plates at 4000 cells/well along with 0.5 μg/mL doxycycline to induce the F508del CFTR-HRP expression and further incubated at 37 °C, 5% CO2 for 72 h. The test compounds were then added at the required concentrations and further incubated for 18–24 h at 33 °C. The highest concentration tested was 20 μM with an 8-point concentration response curve using a 3-fold dilution. Three replicate plates were run to determine one EC50. All plates contained negative controls (dimethyl sulfoxide, DMSO) and positive controls (3 μM of 3-[(2R,4R)-4-({[1-(2,2-difluoro-1,3-benzodioxol-5-yl)cyclopropyl]carbonyl}amino)-7-methoxy-3,4-dihydro-2H-chromen-2-yl]benzoic acid) (Compound 15) as well as the on-plate concentration response of the positive control. Post-incubation, the plates were washed 5× times with Dulbecco’s phosphate buffered saline (DPBS), followed by the addition of the HRP substrate, luminol (50 μL), and measuring the HRP activity using luminescence readout on EnVision Multilabel Plate Reader (PerkinElmer; product number 2104-0010). The raw counts from the experiment are analyzed using Accelrys Assay Explorer v3.3.
The % activity measured at each of the eight test concentrations of the test compound was normalized to the on-plate positive control using the following formula:
The maximum % activity achieved for the test compound at any tested concentration is presented in tables along with the EC50 calculated using the general sigmoidal curve with a variable Hill slope equation.

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Cell surface expression (CSE)-HRP assay: CFBE41o- F508del CFTR-HRP cells were plated in 384-well plates at 4000 cells/well with 0.5 μg/mL doxycycline to induce expression, incubated 72 hours at 37°C/5% CO2. Test compounds added at required concentrations (highest 20 μM, 8-12 point concentration-response, 3-fold dilution) and incubated 18-24 hours at 33°C. Plates washed 5× with PBS, luminol (50 μL) added as HRP substrate, luminescence read on plate reader. DMSO as negative control; compound 15 (2-3 μM) as positive control. Percentage activity normalized to positive control: % activity = ((test response - DMSO response)/(positive control response - DMSO response)) × 100. EC50 calculated using sigmoidal curve with variable Hill slope. [2]
Western blot analysis (CFBE cells): CFBE cells stably expressing F508delCFTR (clone DG3) seeded at 10⁶ cells/well in 6-well dishes, treated with DMSO or compound for 18-24 hours at 37°C. Cell monolayers rinsed with cold PBS, lysed with RIPA buffer containing protease inhibitors. Lysates centrifuged at 12,000g for 10 min at 4°C; protein concentration measured by BCA assay. Equal protein amounts electrophoresed on NuPAGE Novex 7% Tris-acetate gels for 2 hours at 150 V; transferred to PVDF membranes at 20 V for 1 hour. Membranes incubated overnight at 4°C with primary mouse monoclonal anti-CFTR 596 antibody (1:5000); secondary antibody (IRDye 800CW goat anti-mouse IgG, 1:15,000) incubated 1 hour at RT in dark. Immunoblots scanned on infrared imaging system and quantified. Mouse monoclonal α-Na/K ATPase antibody (1:5000) used for loading normalization. [2]
Western blot analysis (BHK suppressor mutant cells): BHK-21 cells stably expressing R1S or R1070W F508delCFTR with 3HA tags in fourth extracellular loop seeded at 1×10⁶ cells/well in 6-well dishes, treated with DMSO or 1 μM ABBV-2222 for 18-24 hours at 37°C. Cell lysates prepared as above; 50 μg protein electrophoresed on NuPAGE Novex 3-8% Tris-acetate gels for 2 hours at 150 V; transferred to PVDF membranes at 20 V for 1 hour. Membranes incubated with mouse monoclonal anti-HA antibody (1:5000) overnight at 4°C; secondary antibody (IRDye 800CW goat anti-mouse IgG, 1:15,000) 1 hour at RT. Immunoblots scanned and quantified; mouse monoclonal anti-α-1 Na/K ATPase antibody (1:5000) used for loading normalization. [2]
Transepithelial current clamp (TECC) assay (CFBE-DG3 cells): CFBE41o- cells stably expressing F508delCFTR (clone DG3) cultured in MEM with 10% FBS, 1% penicillin/streptomycin, G418 (0.5 mg/mL) at 37°C/5% CO2. Cells seeded onto collagen-coated 24-well filters at 1.5×10⁶ cells/filter, cultured 5-7 days to form tight monolayer. On measurement day, cells switched to bicarbonate- and serum-free F-12 Coon's medium, equilibrated 180 min in CO2-free incubator. Apical and basolateral sides bathed with F-12 Coon's modification media (20 mM HEPES, pH 7.4), measurements at 36.5°C. Sequential additions: benzamil (apical 6 μM), forskolin (apical and basolateral 10 μM), GLPG1837 (apical and basolateral 1 μM), and bumetanide (basolateral 20 μM). TECC-24 instrument measured transepithelial voltage and resistance; equivalent current (IEQ = VT/RT) calculated. DMSO as negative control; compound 15 (3 μM) as positive control. Percentage activity normalized to positive control. EC50 calculated using sigmoidal curve with variable Hill slope. [2]
TECC assay (primary HBE cells): Primary HBE cells from CF patients homozygous F508del/F508del seeded onto 24-well filter plates coated with 3T3 conditioned media, grown at air-liquid interface for 35 days using differentiation media. Apical mucus removed 72 hours before experiment by incubation with 3 mM dithiothreitol in PBS with Ca²⁺/Mg²⁺ for 30 min, followed by aspiration and PBS wash. Cells incubated with corrector compounds 18-24 hours at 37°C/5% CO2; compounds applied on basolateral side. On measurement day, cells equilibrated 30 min in CO2-free incubator. Same sequential additions and calculations as CFBE-DG3 TECC assay. [2]
Patch-clamp electrophysiology: CHO cells transiently transfected with CFTR-cDNA and GFP encoding pEGFP-C3 incubated with ABBV-2222 overnight before experiments. Inside-out mode patch-clamp experiments performed; F508delCFTR activated by protein kinase A and ATP. Single channel kinetic analysis used to determine open probability (Po). [2]
MSD1 fragment stabilization assay: HEK293 cells transfected with CFTR fragments of different lengths (370X, 373X, 375X, 380X, etc.) using Effectene reagent. Modulators (5 μM) added 14 hours prior to harvest; cycloheximide (10 μg/mL) used in chase experiments. CFTR fragment expression detected by Western blot with CFTR N-terminal tail antibody (MM13-4); bortezomib (10 μM, 4 hours prior to harvest) used as proteasome inhibitor control. [2]

Pharmacokinetic studies were performed using rats.

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Cell Surface Expression-Horseradish Peroxidase (CSE-HRP) Assay: CFBE41o- F508del CFTR-HRP cells were plated in 384-well plates at 4,000 cells/well with 0.5 µg/mL doxycycline to induce F508del CFTR-HRP expression, and incubated at 37°C, 5% CO2 for 72 hours. Test compounds (including ABBV-2222) were added at required concentrations (highest concentration 20 µM with 8-point concentration-response curve using 3-fold dilution) and further incubated for 18-24 hours at 33°C. Plates were washed 5 times with DPBS, followed by addition of luminol (50 µL) as HRP substrate. HRP activity was measured using luminescence readout on a plate reader. Raw counts were analyzed and percentage activity was normalized to on-plate positive control (compound 15, 3 µM) and DMSO negative control. EC50 values were calculated using a general sigmoidal curve with variable Hill slope equation. [1]
Trans-epithelial Current Clamp on Human Bronchial Epithelial Cells (HBE-TECC) Assay: Primary human bronchial epithelial cells from F508del/F508del CFTR patients were expanded and seeded onto 24-well filter plates coated with 3T3 conditioned media and grown at air-liquid interface for 35 days using differentiation media. Apical mucus was removed 72 hours before experiment by incubating with 3 mM DTT for 30 minutes, followed by aspiration and re-wash. Cells were incubated with desired concentrations of ABBV-2222 or other correctors (prepared from 10 mM stocks in differentiation media) on the basolateral side for 18-24 hours at 37°C, 5% CO2. On the day of measurement, cells were switched to bicarbonate- and serum-free F-12 Coon's medium and equilibrated for 90 minutes in a CO2-free incubator. Measurements were made at 36.5°C using a TECC-24 instrument. Apical and basolateral sides were bathed with F-12 Coon's medium (20 mM HEPES, pH 7.4). Current responses were measured before and after sequential addition of benzamil (apical, 6 µM), forskolin (apical and basolateral, 10 µM), control potentiator GLPG1837 (apical and basolateral, 1 µM), and bumetanide (basolateral, 20 µM). Transepithelial potential difference (VT) and conductance (GT) were measured under current clamp conditions. Equivalent current (IEQ = VT·GT) and area under the curve were calculated. Percentage activity was normalized to on-plate positive control (3 µM compound 15) and DMSO negative control. EC50 was calculated using a general sigmoidal curve with variable Hill slope equation in Prism v5. [1]

Table 7 lists the pharmacokinetic characteristics of Galicaftor (ABBV-2222; GLPG-2222). Galicaftor (ABBV-2222; GLPG-2222) is mainly cleared from human plasma via glucuronidation, thus the risk of drug interaction is low. Comprehensive preclinical studies in rats and dogs, including pharmacokinetic (DMPK), safety pharmacology, and toxicology, support Galicaftor (ABBV-2222; GLPG-2222) as a candidate for clinical development. In a first-in-human Phase I study, healthy volunteers were given a single dose of up to 800 mg of Galicaftor (ABBV-2222; GLPG-2222) and multiple daily doses of up to 600 mg for 14 days. The drug was well tolerated and had a high safety profile, with no cases of premature discontinuation of the study drug and no serious adverse events. [1]

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Rat pharmacokinetic study: Compound 15 (precursor) was characterized in rat PK studies at IV dose 1.2 mg/kg (clearance 2.8 L/h/kg, half-life 2.1 h) and oral dose 12 mg/kg (bioavailability 42%). Compound 21 was characterized at IV dose 1 mg/kg (clearance 0.6 L/h/kg, half-life 4.4 h) and oral dose 17 mg/kg (bioavailability 8%). [1]
Rat PK for compound 22: IV dose 1 mg/kg, clearance 0.55 L/h/kg, half-life 2.7 h; oral dose 2 mg/kg, bioavailability 74%. [1]
Dog PK for compound 22: IV dose 2 mg/kg, clearance 0.83 L/h/kg, half-life 5.0 h; oral dose 5 mg/kg, bioavailability 40%. [1]

ABBV-2222 does not show nonproductive interactions with potentiators at clinically relevant concentrations (unlike lumacaftor which shows such interactions with ivacaftor at high nonphysiologically relevant concentrations). [2]
ABBV-2222 showed no CYP3A4 induction (in contrast to lumacaftor which is a CYP3A4 inducer). [2]
ABBV-2222 does not cause bronchoconstriction (in contrast to lumacaftor which has been reported to cause bronchoconstriction in some patients due to off-target effects). [2]
ABBV-2222 is selective for F508delCFTR and does not affect processing of other misfolded proteins (hERG G601S, PgP G268V). [2]
No specific toxicity data (LD50, organ toxicity, protein binding) were reported in this study. [2]

[1]. Discovery of 4-[(2R,4R)-4-({[1-(2,2-Difluoro-1,3-benzodioxol-5-yl)cyclopropyl]carbonyl}amino)-7-(difluoromethoxy)-3,4-dihydro-2H-chromen-2-yl]benzoic Acid (ABBV/GLPG-2222), a Potent Cystic Fibrosis Transmembrane Conductance Regulator.

[2]. Biological Characterization of F508delCFTR Protein Processing by the CFTR Corrector ABBV-2222/GLPG2222. J Pharmacol Exp Ther. 2020 Jan;372(1):107-118.

Galicaftor is being investigated in the clinical trial NCT03540524 (a study designed to evaluate the safety, tolerability and efficacy of the investigational drugs GLPG2451 and GLPG2222 with or without GLPG2737 in patients with cystic fibrosis).

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CF is caused by loss-of-function mutations in the CFTR gene; the most prevalent mutation F508del (deletion of phenylalanine 508) is present on at least one allele in ~90% of CF patients. [2]
Two biomolecular activities are required to treat F508delCFTR: correctors to increase properly folded protein at cell surface, and potentiators to allow effective channel opening. [2]
ABBV-2222 is a type C1 corrector that functions by promoting stabilization of the interface between NBD1 and MSD2 (nucleotide binding domain 1 / membrane-spanning domain 2). [2]
Triple combination therapy (two correctors with additive mechanisms + one potentiator) is expected to attain greater clinical benefits for CF patients. [2]
First-generation C1 correctors lumacaftor (VX-809) and tezacaftor (VX-661) were developed by Vertex Pharmaceuticals; ORKAMBI (lumacaftor + ivacaftor) and SYMDEKO (tezacaftor + ivacaftor) are FDA-approved but show only modest (~3-4%) FEV1 improvements. [2]
Lumacaftor liabilities include: CYP3A4 induction, bronchoconstriction in some patients, and 25-30% discontinuation rate in first 3 months. [2]
ABBV-2222 represents a novel C1 corrector as the first component of triple combination therapy being developed by AbbVie; it is currently in clinical trials. [2]
ABBV-2222 does not show additivity with lumacaftor or tezacaftor, consistent with similar mechanism of action (all are C1 correctors). [2]
Ongoing efforts are focused on understanding mechanism of action and drug-drug interactions of triple combination components to produce best-in-class therapy for CF patients. [2]

C28H21F4NO7

559.462462186813

559.125

C, 60.11; H, 3.78; F, 13.58; N, 2.50; O, 20.02

1918143-53-9

121301049

White to off-white solid powder

1.6±0.1 g/cm3

701.1±60.0 °C at 760 mmHg

377.8±32.9 °C

0.0±2.3 mmHg at 25°C

1.640

6.05

2

11

7

40

957

2

FC1(OC2=CC=C(C=C2O1)C1(C(N[C@H]2C3C=CC(=CC=3O[C@@H](C3C=CC(C(=O)O)=CC=3)C2)OC(F)F)=O)CC1)F

QVDYQHXNAQHIKH-TZIWHRDSSA-N

InChI=1S/C28H21F4NO7/c29-26(30)37-17-6-7-18-19(13-21(38-22(18)12-17)14-1-3-15(4-2-14)24(34)35)33-25(36)27(9-10-27)16-5-8-20-23(11-16)40-28(31,32)39-20/h1-8,11-12,19,21,26H,9-10,13H2,(H,33,36)(H,34,35)/t19-,21-/m1/s1

4-((2R,4R)-4-(1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)cyclopropane-1-carboxamido)-7-(difluoromethoxy)chroman-2-yl)benzoic acid

GLPG-2222; Galicaftor; 1918143-53-9; ABBV-2222; GLPG2222; Galicaftor [INN]; Galicaftor [USAN]; GLPG 2222; J0IIT8QSQS; ABBV-2222; Galicaftor; ABBV 2222; GLPG2222; ABBV2222.

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~50 mg/mL (~89.37 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (4.47 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (4.47 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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 (Please use freshly prepared in vivo formulations for optimal results.)