Posenacaftor (PTI-801) is a cystic fibrosis transmembrane regulatory protein (CFTR) modulator that corrects the folding and trafficking of CFTR protein. Posenacaftor may be used in cystic fibrosis (CF) research.

Physicochemical Properties

Molecular Formula	C27H27NO5
Molecular Weight	445.506987810135
Exact Mass	445.188
CAS #	2095064-05-2
Related CAS #	Posenacaftor sodium;2095064-06-3
PubChem CID	129027688
Appearance	Typically exists as solid at room temperature
LogP	5.5
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	6
Rotatable Bond Count	5
Heavy Atom Count	33
Complexity	681
Defined Atom Stereocenter Count	1
SMILES	CC1=C2C(=C(C=C1)O[C@H](C)C3CCOCC3)C(=CC(=N2)C4=C(C5=CC=CC=C5O4)C)C(=O)O
InChi Key	QUDOHCFOJCNKPK-QGZVFWFLSA-N
InChi Code	InChI=1S/C27H27NO5/c1-15-8-9-23(32-17(3)18-10-12-31-13-11-18)24-20(27(29)30)14-21(28-25(15)24)26-16(2)19-6-4-5-7-22(19)33-26/h4-9,14,17-18H,10-13H2,1-3H3,(H,29,30)/t17-/m1/s1
Chemical Name	8-methyl-2-(3-methyl-1-benzofuran-2-yl)-5-[(1R)-1-(oxan-4-yl)ethoxy]quinoline-4-carboxylic acid
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	The autosomal recessive illness known as cystic fibrosis (CF) is brought on by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR)[1]. The CFTR chloride channel is typically found at the apical membrane of epithelial cells and is controlled by cAMP. A malfunctioning and misfolded CFTR protein is produced when the CFTR gene is mutated, which hinders the movement of ions into and out of cells[1]. Posenacaftor is a CFTR corrector; correctors are made to correct and restore the CFTR protein's malfunction. After then, the modified CFTR travels to the cell surface, where it serves as a chloride channel and aids in preserving the proper fluid balance in the airways[2].
References	[1]. Compositions et procédés pour améliorer la fonction cftr dans des cellules affectées par la fibrose kystique. Patent WO2019156946. [2]. Posenacaftor (PTI-801).
Additional Infomation	PTI-801 represents a new class of drugs to treat pain. PTI-801 can minimize the opioid tolerance, dependence or addiction that is often associated with repeat use of oxycodone. It is a combination of oxycodone with ultralow-dose naltrexone, an opioid antagonist. Drug Indication Investigated for use/treatment in addictions, osteoarthritis, and pain (acute or chronic). Mechanism of Action PTI-801 is a novel form of oxycodone that minimizes the abuse and drug dependence that is often associated with oxycodone and other narcotic painkillers. The goal of developing PTI-801 is to ensure the safety of patients who have a legitimate medical need to treat severe chronic pain with a narcotic painkiller, and to protect the public from the consequences of abuse.

Solubility Data

Solubility (In Vitro)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

Solubility (In Vivo)

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples. Injection Formulations (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] *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. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Oral Formulations Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.2446 mL	11.2231 mL	22.4462 mL
	5 mM	0.4489 mL	2.2446 mL	4.4892 mL
	10 mM	0.2245 mL	1.1223 mL	2.2446 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.