Icenticaftor (QBW251) is an orally bioactive CFTR channel enhancer with EC50s of 79 nM and 497 nM for F508del and G551D CFTR, respectively. Icenticaftor may be used in chronic obstructive pulmonary disease (COPD) and cystic fibrosis research.

Physicochemical Properties

Molecular Formula	C12H13F6N3O3
Molecular Weight	361.240343809128
Exact Mass	361.09
Elemental Analysis	C, 39.90; H, 3.63; F, 31.55; N, 11.63; O, 13.29
CAS #	1334546-77-8
Related CAS #	1334546-77-8;
PubChem CID	58442344
Appearance	White to yellow solid powder
LogP	2.2
Hydrogen Bond Donor Count	3
Hydrogen Bond Acceptor Count	11
Rotatable Bond Count	4
Heavy Atom Count	24
Complexity	458
Defined Atom Stereocenter Count	1
SMILES	C[C@](CNC(=O)C1=C(C=C(C(=N1)OC)C(F)(F)F)N)(C(F)(F)F)O
InChi Key	USHQRIKZLHNPQR-JTQLQIEISA-N
InChi Code	InChI=1S/C12H13F6N3O3/c1-10(23,12(16,17)18)4-20-8(22)7-6(19)3-5(11(13,14)15)9(21-7)24-2/h3,23H,4,19H2,1-2H3,(H,20,22)/t10-/m0/s1
Chemical Name	3-amino-6-methoxy-N-[(2S)-3,3,3-trifluoro-2-hydroxy-2-methylpropyl]-5-(trifluoromethyl)pyridine-2-carboxamide
Synonyms	Icenticaftor; QBW251; QBW 251; QBW-251;
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

ln Vitro	Icenticaftor (QBW251) is a small molecule CFTR enhancer that may be taken orally and is bioavailable. It has the ability to restore CFTR function in both wild-type and particular CFTR genotypes [2].
ln Vivo	The pharmacokinetic profile of Icenticaftor was developed in Sprague-Dawley rats. After an oral dosage of 3 mg/kg, the oral bioavailability is 90% and the AUClast is 20 635 nmol/L·h[1].
References	[1]. Discovery of Icenticaftor (QBW251), a Cystic Fibrosis Transmembrane Conductance Regulator Potentiator with Clinical Efficacy in Cystic Fibrosis and Chronic Obstructive Pulmonary Disease. J Med Chem. 2021 Jun 10;64(11):7241-7260. [2]. Efficacy and Safety of the CFTR Potentiator Icenticaftor (QBW251) in COPD: Results from a Phase 2 Randomized Trial. Int J Chron Obstruct Pulmon Dis. 2020 Oct 5;15:2399-2409.

Solubility Data

Solubility (In Vitro)

DMSO : ~150 mg/mL (~415.24 mM)

Solubility (In Vivo)

Solubility in Formulation 1: 4.25 mg/mL (11.77 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 42.5 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. Solubility in Formulation 2: ≥ 4.25 mg/mL (11.77 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in 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 42.5 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 3: ≥ 4.25 mg/mL (11.77 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 42.5 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.7682 mL	13.8412 mL	27.6824 mL
	5 mM	0.5536 mL	2.7682 mL	5.5365 mL
	10 mM	0.2768 mL	1.3841 mL	2.7682 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.