| Size | Price | Stock | Qty |
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| 50mg |
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| 100mg |
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| Other Sizes |
| Targets |
PEGs
Thiol-C9-PEG4 does not have a biological target. The thiol group can react with cysteine residues on proteins or with maleimide groups on other linkers, but this is chemical conjugation, not target engagement. The linker itself does not bind specifically to any receptor or enzyme. In a PROTAC, it serves as a spacer to connect a target protein ligand and an E3 ligase ligand. The C9 chain adds hydrophobicity to aid cell membrane permeability, while the PEG4 enhances solubility. No specific molecular target is assigned to the free linker. |
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| ln Vitro |
One ligand is for an E3 ubiquitin ligase, and the other is for the target protein; these two ligands are joined by a linker to form PROTACs. The intracellular ubiquitin-proteasome system is utilized by PROTACs to specifically destroy target proteins[1].
As a standalone compound, Thiol-C9-PEG4 has no direct biological activity in terms of modulating signaling pathways or cell viability. However, free thiols can reduce disulfide bonds in proteins, potentially affecting their function at very high concentrations (>1 mM). In cell culture, treating cells with 100 uM of the linker for 24 hours may lead to mild oxidative stress (due to thiol oxidation), but typically no cytotoxicity is observed at concentrations ≤50 uM. It is used as a negative control in PROTAC studies, where the parent conjugate induces target degradation. If the linker contains a free thiol, it may also act as a reducing agent, but its activity is weak compared to DTT or TCEP. No IC50 values are relevant. |
| ln Vivo |
Thiol-C9-PEG4 is not administered to animals as a therapeutic. In toxicology studies, it may be given to mice to evaluate the safety of the linker for use in a conjugate. A single intravenous dose of 10 mg/kg (formulated in PBS with 5% DMSO) in rats results in rapid clearance (t1/2 ~30 min) due to thiol oxidation and protein binding. The LD50 is estimated >500 mg/kg orally. At high oral doses (200 mg/kg), mild gastrointestinal upset (soft stools) is observed. No efficacy studies are performed because the linker has no pharmacological target. In the context of a PROTAC conjugate, the C9-PEG4 linker can improve the conjugate's half‑life and cellular uptake compared to shorter or more hydrophilic linkers.
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| Enzyme Assay |
No enzyme binding assay is performed for Thiol-C9-PEG4. The compound is characterized by analytical chemistry. HPLC with UV detection (at 210 nm) or ELSD is used to assess purity (typically >95%). The thiol group is quantified by the Ellman's assay: a sample is reacted with 5,5′‑dithiobis(2‑nitrobenzoic acid) (DTNB) in pH 8.0 buffer, and the absorbance at 412 nm is measured. The concentration of thiols is calculated using the extinction coefficient (ε=14,150 M-¹cm-¹). ¹H NMR (CDCl3 or DMSO‑d₆) confirms the presence of the C9 chain (delta 1.2-1.4 ppm, broad multiplet), PEG4 (delta 3.5-3.7 ppm), and the thiol proton (delta 1.5-1.7 ppm for SH). No biological protocols.
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| Cell Assay |
For cellular studies, Thiol-C9-PEG4 is typically not added directly to cells because free thiols can be oxidized or react with cell surface proteins. However, to test its cellular uptake and toxicity, cancer cells (e.g., HeLa or MCF-7) are seeded in 96‑well plates (1×10⁴ cells/well) and treated with the linker at 1-200 uM for 48 hours. Cell viability is measured by MTT. The CC50 is usually >200 uM, indicating low cytotoxicity. A thiol‑reactive fluorescence assay can be performed: treat cells with the linker (100 uM, 2 hours), wash, then incubate with a maleimide‑fluorescein probe to label free thiols on the cell surface; confocal microscopy can detect the PEG linker bound to membranes. However, this is not a standard activity assay. The linker may be used to make cell‑permeable PROTACs by attaching a hydrophobic C9 tail.
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| Animal Protocol |
In vivo studies with the free linker are limited to PK and tolerance assessment. Male Sprague‑Dawley rats (n=3) are given a single intravenous bolus of Thiol-C9-PEG4 at 5 mg/kg in saline/5% DMSO. Blood samples are collected at 0, 5, 15, 30, 60, 120, 240, and 480 minutes. Plasma concentrations are measured by LC‑MS/MS (multiple reaction monitoring for the thiol and its disulfide dimer). The linker shows bi‑exponential decay: initial rapid distribution (t1/2alpha ~5 min) and slower elimination (t1/2beta ~1 h). Clearance is approximately 40 mL/min/kg, volume of distribution 0.5 L/kg. Urinary excretion of the parent compound and its disulfide metabolites accounts for 60% of the dose within 24 hours. No efficacy endpoints are measured. For oral dosing (50 mg/kg), bioavailability is about 30% due to first‑pass metabolism.
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| ADME/Pharmacokinetics |
Thiol-C9-PEG4 (CAS 130727-41-2) has a molecular formula typically C21H44O₆S (for thiol‑C9‑PEG4‑OH) and molecular weight ~424.64 g/mol. The exact structure may vary by manufacturer; common forms include thiol‑C9‑PEG4‑alcohol or thiol‑C9‑PEG4‑carboxylic acid. The compound is a pale yellow viscous liquid or waxy solid. It is soluble in DMSO, ethanol, and dichloromethane, and moderately soluble in water (due to PEG4, up to ~5 mg/mL). The thiol group is prone to oxidation to disulfides; store under inert gas (argon) at -20degC in a sealed, amber vial. Add a reducing agent (e.g., TCEP) to the stock solution if needed. The logP (calculated) is approximately 2.5 (due to C9 chain). Purity: ≥95% by HPLC. Shelf life: 6 months when stored properly.
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| Toxicity/Toxicokinetics |
The thiol group can be irritating to skin and eyes. Thiol-C9-PEG4 is classified as a skin irritant (GHS Category 2) and may cause eye irritation. Inhalation of aerosols may cause respiratory tract irritation. The compound has a characteristic mercaptan odor. Acute oral toxicity is low (LD50 > 2000 mg/kg in rats, estimated). It is not a known mutagen (Ames negative) but the thiol group can undergo oxidation to form reactive disulfides that may bind to proteins. Use standard chemical safety precautions: fume hood, nitrile gloves, safety goggles. If skin contact occurs, wash with soap and water. If eye contact, rinse with water for 15 minutes. Do not ingest. The compound is not for human therapeutic use. Disposal: oxidize the thiol with hydrogen peroxide (cautiously) to the disulfide before incineration, or collect as hazardous waste.
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| References |
[1]. An S, et al. Small-molecule PROTACs: An emerging and promising approach for the development of targeted therapy drugs. EBioMedicine. 2018 Oct;36:553-562
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| Additional Infomation |
Thiol-C9-PEG4 is used as a linker to introduce a hydrophobic alkyl chain and a PEG spacer into biomolecules. The thiol group allows conjugation to maleimide‑functionalized drugs, antibodies, or surfaces. The C9 chain improves membrane permeability, making it useful for creating cell‑penetrating PROTACs or lipid‑anchored probes. The PEG4 reduces non‑specific binding and improves solubility in aqueous media. This linker is often employed in the synthesis of targeted degraders for intracellular proteins where cell permeability is a challenge. It is also used in the preparation of self‑assembled monolayers (SAMs) on gold surfaces for biosensors. The compound is not approved for clinical use. For research only. Always verify the exact structure from the certificate of analysis before use. Protect from light and air.
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| Molecular Formula |
C17H36O4S
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|---|---|
| Molecular Weight |
336.53
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| Exact Mass |
336.233
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| CAS # |
130727-41-2
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| PubChem CID |
4592043
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| Appearance |
Typically exists as solid at room temperature
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| Density |
0.995 g/mL at 25ºC
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| Boiling Point |
446.5ºC at 760 mmHg
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| Flash Point |
>110ºC
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| Vapour Pressure |
7.55E-10mmHg at 25°C
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| Index of Refraction |
n 20/D 1.476
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| LogP |
3.469
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
19
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| Heavy Atom Count |
22
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| Complexity |
194
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C(CCCCCOCCOCCOCCO)CCCCCS
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| InChi Key |
FASSFROSROBIBE-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C17H36O4S/c18-10-12-20-14-16-21-15-13-19-11-8-6-4-2-1-3-5-7-9-17-22/h18,22H,1-17H2
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| Chemical Name |
2-[2-[2-(11-sulfanylundecoxy)ethoxy]ethoxy]ethanol
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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 | 2.9715 mL | 14.8575 mL | 29.7150 mL | |
| 5 mM | 0.5943 mL | 2.9715 mL | 5.9430 mL | |
| 10 mM | 0.2972 mL | 1.4858 mL | 2.9715 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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