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| Targets |
PG‑01 directly targets the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel, a cAMP‑dependent ion channel protein located on the apical membrane of various epithelial cells. Dysfunction of CFTR, mainly due to genetic mutations, is the root cause of cystic fibrosis. PG‑01 binds to the CFTR protein, corrects the gating defects of multiple mutants (including ΔF508, E193K, G970R, G551D, and G1349D), and effectively restores channel function. In addition, studies have shown that PG‑01 can partially correct the trafficking deficiency of hERG mutant proteins.
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| ln Vitro |
While PG01 alone does not activate ΔF508-CFTR, the addition of 0.5 and 2 μM Forskolin causes significant ΔF508-CFTR Cl-currents. Channel activity was substantially increased by PG01 at 100 nM, and numerous channel openings were seen. PG01's apparent Kd for G551D-CFTR activation is 1 μM, which is around 100 times more effective than genistein's. At 40 nM, PG01's activation potency over G1349D-CFTR was considerably greater. When G551D and G1349D-CFTR are expressed in cells, PG01 produces significant currents. This current is not present in untransfected cells and is sensitive to CFTRinh-172 [1].
PG‑01 exhibits high in vitro potency against various CFTR mutants. It displays a Ka value of 0.3 μM against the ΔF508 mutant, a Kd of 0.22 μM against E193K, 0.45 μM against G970R, and 1.94 μM against G551D. In electrophysiological assays, the apparent Kd for G551D‑CFTR activation is approximately 1 μM, showing about 100‑fold greater potency than genistein. The potency for G1349D‑CFTR activation is even higher, requiring only 40 nM. At a concentration of 100 nM, PG‑01 markedly enhances ΔF508‑CFTR channel activity with frequent channel openings. In the presence of forskolin, PG‑01 significantly increases ΔF508‑CFTR Cl⁻ currents, and these currents are blocked by the CFTR‑selective inhibitor CFTRinh‑172. |
| ln Vivo |
Rats receiving a single bolus injection of PG01 (5 mg/kg) had their plasma concentrations serially measured to conduct a pharmacokinetic analysis. PG01's pharmacokinetics, which have a distribution volume of 4L and half-lives of less than 5 minutes and 130 minutes, are in line with the two-compartment model. Research on microsomal metabolism and rat pharmacokinetics demonstrate that PG01's metabolism is substantially quicker than SF-03's[1].
The in vivo pharmacokinetics of PG‑01 have been preliminarily investigated in animal models. In rats, following a single intravenous bolus dose of 5 mg/kg, the pharmacokinetic profile fits a two‑compartment model with elimination half‑times of <5 min and 130 min, and an apparent volume of distribution of approximately 4 L. Moreover, microsome metabolism studies and rat pharmacokinetic analysis indicate that PG‑01 is metabolized significantly faster in vivo than the reference compound SF‑03. |
| Enzyme Assay |
In vitro assessment of PG‑01‘s activity on CFTR chloride channels is commonly performed using fluorescence‑based assays or patch‑clamp techniques. In a non‑cell system, purified CFTR protein, or membrane vesicles containing CFTR, are reconstituted into artificial membranes such as planar lipid bilayers. The standard protocol involves: clamping the voltage across the bilayer (typically from −60 mV to +60 mV) to record transmembrane currents; after stabilization, incubating the bath solution with a series of PG‑01 concentrations for 5–10 minutes; monitoring and quantifying the resulting current amplitude changes; and calculating the affinity constants (Ka or Kd) of PG‑01 for the CFTR channel.
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| Cell Assay |
Cell‑based in vitro experiments are typically carried out using mammalian cell lines expressing various mutant CFTR constructs, such as HEK‑293, COS‑7, and Fisher rat thyroid epithelial cells. A representative protocol is as follows: Cells stably or transiently transfected with mutant CFTR are seeded in culture plates suitable for electrophysiological recording and cultured for 24–48 hours. On the day of the experiment, whole‑cell patch‑clamp or fluorescence quenching assays are used to evaluate chloride channel function. After recording baseline currents, increasing concentrations of PG‑01 (e.g., 0.01–10 μM) are applied to the extracellular solution, with forskolin (0.5–2 μM) added as a positive control. The enhancement of chloride currents by PG‑01 is recorded. To confirm specificity, the CFTR‑selective inhibitor CFTRinh‑172 is applied at the end of the experiment to verify that the recorded currents originate from CFTR channels. All experiments are repeated at least three independent times (with n ≥ 3 per batch), and data are subjected to statistical analysis.
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| Animal Protocol |
In vivo pharmacokinetic studies of PG‑01 are commonly conducted in Sprague‑Dawley rats. A typical protocol is as follows: Male SD rats (200–250 g body weight) are randomly divided into groups and given a single intravenous bolus dose of PG‑01 (5 mg/kg). Blood samples are collected from the jugular or tail vein at predetermined time points (e.g., 0, 5, 10, 20, 30, 60, 120, 180, 240 minutes, and 6 hours post‑dose). Plasma is immediately separated by centrifugation, and drug concentrations are quantified by LC‑MS/MS. The plasma concentration‑time curve is constructed, and key pharmacokinetic parameters (t₁/₂, CL, Vd, AUC, etc.) are calculated using non‑compartmental or two‑compartmental modeling.
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| Toxicity/Toxicokinetics |
Publicly available toxicological information on PG‑01 is limited. According to safety data (e.g., SDS information for Phenylglycine‑01), the acute toxicity of this compound is classified as GHS Category 4 (oral), indicating potential harm if swallowed. During handling and storage, it is recommended to avoid inhaling dust or vapor, prevent contact with skin and eyes, use appropriate personal protective equipment (such as chemical‑resistant gloves and goggles), and maintain adequate ventilation. To date, no comprehensive, peer‑reviewed toxicology reports—including repeated‑dose toxicity, carcinogenicity, or reproductive/developmental toxicity—have been published for PG‑01.
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| References |
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| Molecular Formula |
C28H29N3O2
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| Molecular Weight |
439.54876
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| Exact Mass |
439.226
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| CAS # |
853138-65-5
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| PubChem CID |
4695397
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| Appearance |
White to off-white solid powder
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| Density |
1.217g/cm3
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| Boiling Point |
704.6ºC at 760 mmHg
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| Flash Point |
379.9ºC
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| Index of Refraction |
1.662
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| LogP |
5.745
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
2
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
33
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| Complexity |
652
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
PQAYCXMQTUEDRD-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C28H29N3O2/c1-19(2)20-13-15-23(16-14-20)30-28(33)27(21-9-5-4-6-10-21)31(3)26(32)17-22-18-29-25-12-8-7-11-24(22)25/h4-16,18-19,27,29H,17H2,1-3H3,(H,30,33)
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| Chemical Name |
2-[[2-(1H-indol-3-yl)acetyl]-methylamino]-2-phenyl-N-(4-propan-2-ylphenyl)acetamide
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| HS Tariff Code |
2934.99.9001
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| 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)
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| 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
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| 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
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *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). View More
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)] 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). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.2751 mL | 11.3753 mL | 22.7505 mL | |
| 5 mM | 0.4550 mL | 2.2751 mL | 4.5501 mL | |
| 10 mM | 0.2275 mL | 1.1375 mL | 2.2751 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.
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.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT05539105 | RECRUITING | Procedure: Double tract reconstruction Procedure: Gastric conduit reconstruction Procedure: Other reconstructions |
Proximal Gastric Adenocarcinoma Reconstruction |
Shanghai Zhongshan Hospital | 2022-08-22 | |
| NCT01867073 | UNKNOWN STATUS | Other: Biomarker | Advanced Solid Tumors | National University Hospital, Singapore | 2011-05 | |
| NCT00941200 | UNKNOWN STATUS | Biological: Blood collection | Cancer | National University Hospital, Singapore | 2009-04 | |
| NCT06494956 | NOT YET RECRUITING | Procedure: Implant device | Parkinson Disease Dementia | Jiangsu CED Medtech Co., Ltd | 2024-07-01 | Not Applicable |
| NCT02205320 | UNKNOWN STATUS | Biological: DRL_PG Biological: Pegfilgrastim Form A Biological: Pegfilgrastim Form B |
Pharmacokinetics | Dr. Reddy's Laboratories Limited | 2014-02 | Phase 1 |
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