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| 5mg |
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| Targets |
The primary target of PGP-4008 is P-glycoprotein (P-gp), also known as multidrug resistance protein 1 (MDR1) or ABCB1. P-gp is an ATP-binding cassette (ABC) transporter that functions as an efflux pump, actively transporting a wide range of xenobiotics and chemotherapeutic drugs out of cells. Overexpression of P-gp is a major mechanism of multidrug resistance in cancer cells. PGP-4008 acts as a selective and potent inhibitor of P-gp, blocking its efflux function and allowing chemotherapeutic drugs to accumulate in cancer cells. The compound shows selectivity for P-gp over MRP1.
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| ln Vitro |
In vitro, PGP-4008 is a selective and potent P-gp inhibitor that does not affect the activity of MRP1. By inhibiting P-gp-mediated drug efflux, the compound increases the intracellular accumulation of chemotherapeutic agents such as doxorubicin. This potentiation of drug activity can overcome P-gp-mediated multidrug resistance in cancer cells. PGP-4008 is effective in vitro, demonstrating its ability to block P-gp function in cell-based assays.
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| ln Vivo |
In vivo, PGP-4008 inhibits tumor growth when administered in combination with doxorubicin in a mouse syngeneic P-gp-mediated multidrug resistance (MDR) solid tumor model. When delivered intraperitoneally, the compound enhances the anti-tumor efficacy of doxorubicin. This demonstrates the compound's ability to overcome P-gp-mediated drug resistance in vivo. PGP-4008 has potential applications in overcoming drug resistance in cancers such as leukemia, breast cancer, and lung cancer.
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| Enzyme Assay |
For P-gp inhibitors, standard cell-free assays involve measuring the ATPase activity of recombinant P-gp in membrane preparations. The compound's ability to stimulate or inhibit P-gp ATPase activity is measured by detecting inorganic phosphate release. Alternatively, radioligand binding assays using [³H]-labeled P-gp substrates or inhibitors can be performed to assess binding affinity.
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| Cell Assay |
For P-gp inhibitors, standard cellular assays involve treatment of P-gp-overexpressing cancer cell lines (e.g., Caco-2, MDCK-MDR1, or drug-resistant cancer cells) with the test compound in the presence of a fluorescent P-gp substrate (e.g., rhodamine 123, calcein-AM) or a radiolabeled chemotherapeutic drug. The accumulation of the substrate or drug in cells is measured by flow cytometry or scintillation counting to assess P-gp inhibition.
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| Animal Protocol |
For in vivo evaluation of P-gp inhibitors, standard animal models include syngeneic or xenograft tumor models using P-gp-overexpressing drug-resistant cancer cell lines. The compound is typically administered intraperitoneally or orally in combination with a chemotherapeutic drug (e.g., doxorubicin) for 2-4 weeks. Tumor growth, drug accumulation in tumors, and survival are assessed. PGP-4008 has been evaluated in a mouse syngeneic P-gp-mediated MDR solid tumor model.
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| ADME/Pharmacokinetics |
PGP-4008 has a molecular weight of 393.5 and formula C26H23N3O. It has a purity of ≥93%. As a small molecule with moderate lipophilicity, it would be expected to have reasonable cell permeability and oral bioavailability. The compound is typically administered intraperitoneally in in vivo studies. Comprehensive pharmacokinetic studies would be required for therapeutic development.
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| Toxicity/Toxicokinetics |
Detailed toxicology data for PGP-4008 is not provided in the available sources. As a research compound targeting P-gp, standard preclinical toxicology would be required for therapeutic development. The compound's selectivity for P-gp over MRP1 suggests a favorable specificity profile. However, potential effects on other ABC transporters or normal tissues expressing P-gp (e.g., intestine, blood-brain barrier, liver) would need to be evaluated. The compound is for research use only and not for therapeutic applications.
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| References | |
| Additional Infomation |
PGP-4008 is a selective and potent P-glycoprotein (P-gp) inhibitor from the dihydropyrroloquinoline class. It does not affect MRP1 activity. PGP-4008 inhibits tumor growth when given with doxorubicin in a mouse syngeneic P-gp-mediated MDR solid tumor model. It has potential applications in overcoming drug resistance in leukemia, breast cancer, and lung cancer. No regulatory approval has been identified.
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| Molecular Formula |
C26H23N3O
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| Molecular Weight |
393.49
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| Exact Mass |
393.184
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| CAS # |
365565-02-2
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| PubChem CID |
9821937
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| Appearance |
White to off-white solid powder
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| LogP |
5.693
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
30
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| Complexity |
569
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
HVIAKQBMYMKWII-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C26H23N3O/c30-24(17-19-9-3-1-4-10-19)28-25-21-13-7-8-14-23(21)27-26-22(25)15-16-29(26)18-20-11-5-2-6-12-20/h1-14H,15-18H2,(H,27,28,30)
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| Chemical Name |
N-(1-benzyl-2,3-dihydropyrrolo[2,3-b]quinolin-4-yl)-2-phenylacetamide
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| Synonyms |
PGP4008; PGP 4008; PGP-4008
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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) |
DMSO : ~62.5 mg/mL (~158.84 mM)
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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 | 2.5414 mL | 12.7068 mL | 25.4136 mL | |
| 5 mM | 0.5083 mL | 2.5414 mL | 5.0827 mL | |
| 10 mM | 0.2541 mL | 1.2707 mL | 2.5414 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.
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