| Targets |
Folate receptor (FR) - specifically folate receptor alpha (FRα), which is overexpressed on many cancer cells including ovarian, breast, lung, and endometrial cancers. Folate-PEG3-C2-acid serves as a targeting ligand for tumor-selective delivery of therapeutic payloads or PROTAC degraders. The folate moiety binds with high affinity to the folate receptor, which is a glycosylphosphatidylinositol (GPI)-anchored cell surface protein that mediates cellular uptake of folate via receptor-mediated endocytosis. By conjugating therapeutic agents to the folate ligand via the PEG3 spacer and amide coupling chemistry, the resulting constructs can be selectively delivered to folate receptor-overexpressing cancer cells, sparing normal tissues that have low folate receptor expression.
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| ln Vitro |
Folate-PEG3-C2-acid is a chemical linker with no direct biological activity. The folate moiety enables binding to folate receptors on cancer cells for targeted delivery, while the PEG3 spacer enhances aqueous solubility and biocompatibility. The compound itself does not induce protein degradation or exert cytotoxic effects; its biological activity is realized only when conjugated to a therapeutic payload (e.g., a small-molecule drug) or a PROTAC molecule. In the context of PROTACs, the folate-targeted linker directs the PROTAC to folate receptor-overexpressing cancer cells, where the PROTAC can induce targeted degradation of a protein of interest.
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| ln Vivo |
Folate-PEG3-C2-acid is used as a building block for synthesizing PROTAC degraders with improved pharmacokinetic properties and tissue-specific activity. It enables tumor-targeted protein degradation via folate receptor-mediated endocytosis. In vivo, folate-targeted PROTACs synthesized using this linker are expected to show enhanced tumor accumulation and reduced off-target effects compared to non-targeted PROTACs. The PEG3 spacer improves aqueous solubility and reduces aggregation, which are important for in vivo efficacy. Detailed in vivo efficacy data for PROTACs synthesized with Folate-PEG3-C2-acid are not provided in the available literature but would depend on the specific PROTAC construct.
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| Enzyme Assay |
Folate receptor binding assays are performed using radiolabeled folate (e.g., 3H-folic acid) or fluorescently labeled folate-PEG conjugates incubated with folate receptor-overexpressing cells (e.g., KB cells, which are derived from nasopharyngeal carcinoma and express high levels of FRα). Competition assays with varying concentrations of Folate-PEG3-C2-acid or folate-targeted conjugates are used to determine binding affinity. Surface plasmon resonance (SPR) can also be used to measure the binding affinity of folate conjugates to recombinant folate receptor. In SPR, the folate receptor is immobilized on a sensor chip, and varying concentrations of the folate conjugate are injected to determine the association and dissociation rate constants.
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| Cell Assay |
Folate receptor-overexpressing cancer cells (e.g., KB, HeLa, OVCAR-3) are treated with folate-PEG3-C2-acid conjugated to therapeutic payloads or PROTACs. Cellular uptake is measured via fluorescence microscopy (if the conjugate includes a fluorescent label) or flow cytometry to assess the efficiency of folate receptor-mediated endocytosis. Cytotoxicity or target protein degradation is assessed to evaluate the efficacy of the folate-targeted conjugate. For PROTACs, target protein levels are measured by Western blotting to confirm degradation, and cell viability is assessed to determine antiproliferative effects. The specificity of folate receptor-mediated uptake is confirmed by competition with excess free folic acid.
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| Animal Protocol |
Mouse xenograft models bearing folate receptor-positive tumors (e.g., KB xenografts) are administered folate-targeted PROTACs or conjugates synthesized using Folate-PEG3-C2-acid. Tumor growth inhibition is measured by caliper measurements of tumor volume. Biodistribution studies are performed to assess tumor accumulation and organ distribution of the folate-targeted conjugate. Target engagement is evaluated by measuring target protein degradation (for PROTACs) in tumor tissue by Western blotting or immunohistochemistry. The efficacy of folate-targeted delivery is compared to non-targeted controls to demonstrate the advantage of folate receptor-mediated targeting.
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| ADME/Pharmacokinetics |
Folate-PEG3-C2-acid is a chemical linker, not a therapeutic agent. The PEG3 spacer improves aqueous solubility (33.33 mg/mL in DMSO, 51.70 mM). In conjugated form, the folate moiety enables receptor-mediated uptake; pharmacokinetic properties depend on the specific payload or PROTAC conjugated to this linker. The PEG3 spacer is expected to increase the hydrodynamic volume and reduce renal clearance, potentially prolonging circulation time. The folate ligand enables active targeting to folate receptor-expressing tissues, which can alter biodistribution. Detailed PK data for conjugates synthesized with Folate-PEG3-C2-acid would depend on the specific construct.
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| Toxicity/Toxicokinetics |
Folate-PEG3-C2-acid is a chemical reagent for research use only; not intended for direct in vivo administration. Standard laboratory safety practices apply. Toxicity depends on the specific therapeutic payload or PROTAC conjugated to this linker. The folate ligand itself is a vitamin (folic acid) with an excellent safety profile. The PEG3 spacer is biocompatible and generally regarded as safe. However, any therapeutic conjugate synthesized using this linker would need to be evaluated for toxicity in preclinical studies.
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| Additional Infomation |
Folate-PEG3-C2-acid is a research-grade PROTAC linker for targeted protein degradation and drug delivery. Molecular formula: C28H36N8O10, molecular weight: 644.63 g/mol. Solubility: 33.33 mg/mL in DMSO. It reacts via standard EDC/NHS amide coupling for immediate use. Synonyms: Folate-PEG3-C2-acid is the acid fragment of Folate-PEG3-NHS ester . Available in standard pack sizes (1 mg, 5 mg, 10 mg, 50 mg, bulk custom). For research use only, not for human therapeutic use.
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| Molecular Formula |
C28H36N8O10
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| Molecular Weight |
644.63
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| Appearance |
Light yellow to yellow solid powder
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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 Note: This product requires protection from light (avoid light exposure) during transportation and storage. |
| 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 :~33.33 mg/mL (~51.70 mM; with heating and sonication.)
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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 | 1.5513 mL | 7.7564 mL | 15.5128 mL | |
| 5 mM | 0.3103 mL | 1.5513 mL | 3.1026 mL | |
| 10 mM | 0.1551 mL | 0.7756 mL | 1.5513 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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