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FDL-169

Alias: FDL-169; FDL169; FDL 169;
Cat No.:V3551 Purity: ≥98%
FDL-169 is a novel and potent CFTR (Cystic fibrosis transmembrane conductance regulator) correctorbeing developed by Flatley Discovery Lab for treating cystic fibrosis (CF) patients who carry the F508del mutation, the most common mutation in this disease.
FDL-169
FDL-169 Chemical Structure CAS No.: 1628416-28-3
Product category: CFTR
This product is for research use only, not for human use. We do not sell to patients.
Size Price Stock Qty
5mg
10mg
25mg
50mg
100mg
250mg
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1g
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Purity & Quality Control Documentation

Purity: ≥98%

Product Description
FDL-169 is a novel and potent CFTR (Cystic fibrosis transmembrane conductance regulator) corrector being developed by Flatley Discovery Lab for treating cystic fibrosis (CF) patients who carry the F508del mutation, the most common mutation in this disease. Correctors are drugs designed to fix and restore the function of the defective CFTR protein. The corrected CFTR then moves to the cell surface, where it functions as a chloride channel and helps maintain the right balance of fluid in the airways.
FDL-169 (CAS#: 1628416-28-3) is a novel and potent CFTR (cystic fibrosis transmembrane conductance regulator) corrector developed by Flatley Discovery Lab for the treatment of cystic fibrosis patients carrying the F508del mutation, the most common mutation in this disease.
Biological Activity I Assay Protocols (From Reference)
Targets
FDL-169 targets the CFTR protein, specifically the F508del mutant form that is misfolded and retained in the endoplasmic reticulum. As a CFTR corrector, it binds to the mutant protein and promotes proper folding and trafficking to the cell surface, where it can function as a chloride channel.
ln Vitro
FDL-169 increases the cell surface abundance of Phe508del CFTR. By correcting the folding defect of the mutant protein, it restores CFTR function and improves chloride transport in airway epithelial cells. The compound is designed to fix and restore the function of the defective CFTR protein.
ln Vivo
In vivo activity data for FDL-169 are limited. As a CFTR corrector, it has potential utility in cystic fibrosis patients with the F508del mutation. The compound would need to be evaluated in animal models of CF or in human clinical trials to demonstrate efficacy in improving lung function and reducing disease complications.
Enzyme Assay
Cell-free assays for FDL-169 are not typically performed as CFTR corrector activity requires the context of the cellular folding and trafficking machinery. Biochemical assays using purified CFTR protein could potentially assess direct binding, but functional correction is best measured in cell-based systems.
Cell Assay
Cells expressing F508del CFTR (e.g., CFBE41o- bronchial epithelial cells or primary human bronchial epithelial cells from CF patients) are treated with FDL-169 at various concentrations. CFTR cell surface expression is assessed by cell surface biotinylation followed by Western blot, or by immunofluorescence. CFTR function (chloride transport) is measured using Ussing chamber or fluorescence-based halide-sensitive dye assays.
Animal Protocol
In vivo animal studies for FDL-169 have not been extensively reported. For CFTR corrector development, studies are typically conducted in mouse models expressing human F508del CFTR or in ferret models. The compound could be administered via oral or inhalation routes. Efficacy endpoints would include CFTR function in airway tissues, lung histology, and survival.
ADME/Pharmacokinetics
Pharmacokinetic properties of FDL-169 have been characterized in preclinical studies. As a small molecule (MW 486.49, formula C27H23FN4O4), it is expected to have reasonable oral bioavailability. The compound is likely metabolized via hepatic pathways. Detailed PK parameters would be available from development studies.
Toxicity/Toxicokinetics
Toxicity data for FDL-169 are limited. As a CFTR corrector, standard toxicological assessments would be required for clinical development. The compound's selectivity for the F508del mutant over wild-type CFTR and other proteins would determine its safety profile. Gastrointestinal and hepatic effects are common with small molecule CFTR modulators.
References
http://www.flatleydiscoverylab.com/fdl169/
Additional Infomation
FDL-169 (molecular formula C27H23FN4O4, MW 486.49) is a novel and potent CFTR corrector developed for cystic fibrosis patients with the F508del mutation. It was developed by Flatley Discovery Lab. The compound is designed to fix and restore the function of the defective CFTR protein. It is intended for research use only.
These protocols are for reference only. InvivoChem does not independently validate these methods.
Physicochemical Properties
Molecular Formula
C27H23FN4O4
Molecular Weight
486.494329690933
Exact Mass
486.17
CAS #
1628416-28-3
PubChem CID
86298861
Appearance
White to off-white solid powder
LogP
4.6
Hydrogen Bond Donor Count
0
Hydrogen Bond Acceptor Count
7
Rotatable Bond Count
6
Heavy Atom Count
36
Complexity
856
Defined Atom Stereocenter Count
0
SMILES
FC1=CC=CC(=C1)C1C2C=CC(=CC=2C(N(CC(N(C)C2=CC=C3C(=C2)OC(C)=N3)=O)N=1)=O)OCC
InChi Key
XRPSUWYWZUQALB-UHFFFAOYSA-N
InChi Code
InChI=1S/C27H23FN4O4/c1-4-35-20-9-10-21-22(14-20)27(34)32(30-26(21)17-6-5-7-18(28)12-17)15-25(33)31(3)19-8-11-23-24(13-19)36-16(2)29-23/h5-14H,4,15H2,1-3H3
Chemical Name
2-(7-ethoxy-4-(3-fluorophenyl)-1-oxophthalazin-2(1h)-yl)-n-methyl-n-(2-methylbenzo[d]oxazol-6-yl)acetamide
Synonyms
FDL-169; FDL169; FDL 169;
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)
Solubility Data
Solubility (In Vitro)
DMSO : ~62.5 mg/mL (~128.47 mM)
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 : PEG300Tween 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).
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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 : PEG300Tween 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).
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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 2.0555 mL 10.2777 mL 20.5554 mL
5 mM 0.4111 mL 2.0555 mL 4.1111 mL
10 mM 0.2056 mL 1.0278 mL 2.0555 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.

Calculator

Molarity Calculator allows you to calculate the mass, volume, and/or concentration required for a solution, as detailed below:

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An example of molarity calculation using the molarity calculator is shown below:
What is the mass of compound required to make a 10 mM stock solution in 5 ml of DMSO given that the molecular weight of the compound is 350.26 g/mol?
  • Enter 350.26 in the Molecular Weight (MW) box
  • Enter 10 in the Concentration box and choose the correct unit (mM)
  • Enter 5 in the Volume box and choose the correct unit (mL)
  • Click the “Calculate” button
  • The answer of 17.513 mg appears in the Mass box. In a similar way, you may calculate the volume and concentration.

Dilution Calculator allows you to calculate how to dilute a stock solution of known concentrations. For example, you may Enter C1, C2 & V2 to calculate V1, as detailed below:

What volume of a given 10 mM stock solution is required to make 25 ml of a 25 μM solution?
Using the equation C1V1 = C2V2, where C1=10 mM, C2=25 μM, V2=25 ml and V1 is the unknown:
  • Enter 10 into the Concentration (Start) box and choose the correct unit (mM)
  • Enter 25 into the Concentration (End) box and select the correct unit (mM)
  • Enter 25 into the Volume (End) box and choose the correct unit (mL)
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  • The answer of 62.5 μL (0.1 ml) appears in the Volume (Start) box
g/mol

Molecular Weight Calculator allows you to calculate the molar mass and elemental composition of a compound, as detailed below:

Note: Chemical formula is case sensitive: C12H18N3O4  c12h18n3o4
Instructions to calculate molar mass (molecular weight) of a chemical compound:
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Definitions of molecular mass, molecular weight, molar mass and molar weight:
  • Molecular mass (or molecular weight) is the mass of one molecule of a substance and is expressed in the unified atomic mass units (u). (1 u is equal to 1/12 the mass of one atom of carbon-12)
  • Molar mass (molar weight) is the mass of one mole of a substance and is expressed in g/mol.
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Reconstitution Calculator allows you to calculate the volume of solvent required to reconstitute your vial.

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  • The answer appears in the Volume (to add to vial) box
In vivo Formulation Calculator (Clear solution)
Step 1: Enter information below (Recommended: An additional animal to make allowance for loss during the experiment)
Step 2: Enter in vivo formulation (This is only a calculator, not the exact formulation for a specific product. Please contact us first if there is no in vivo formulation in the solubility section.)
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Calculation results

Working concentration mg/mL;

Method for preparing DMSO stock solution mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.

Method for preparing in vivo formulation:Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O,mix and clarify.

(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
             (2) Be sure to add the solvent(s) in order.

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