![Methyl 3-(hydroxymethyl)bicyclo[1.1.1]pentane-1-carboxylate](/upload/0319/V113405.png)
| Size | Price | Stock | Qty |
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| 250mg |
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| 500mg |
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| 1g |
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| 5g |
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| 10g |
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| Other Sizes |
| Targets |
As a PROTAC linker, Methyl 3-(hydroxymethyl)bicyclo[1.1.1]pentane-1-carboxylate does not have direct biological targets. Its role is to serve as a rigid, three-dimensional spacer for PROTAC synthesis. The BCP core provides a conformationally constrained scaffold that can improve metabolic stability and target binding selectivity. The hydroxymethyl group and methyl ester provide orthogonal handles for conjugation to target protein ligands and E3 ubiquitin ligase ligands. The BCP scaffold can act as a bioisostere for para-substituted benzene rings, offering enhanced solubility and reduced planarity compared to aromatic linkers.
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| ln Vitro |
PROTAC contains two distinct ligands linked by a single linker: one is the ligand for the E692 ubiquitin ligase, and the other is the ligand for the target protein. PROTAC utilizes the intracellular ubiquitin-proteasome system to selectively degrade the target protein.
This compound does not have direct in vitro biological activity as it is a chemical linker. In PROTAC development, the compound is functionalized at the hydroxymethyl and ester groups to attach target protein ligands and E3 ligase ligands. The resulting PROTAC is evaluated in cellular assays for target protein degradation. The rigid BCP scaffold can enhance ternary complex formation by providing defined spatial orientation of the binding domains, potentially leading to improved degradation potency and selectivity compared to flexible alkyl linkers. |
| ln Vivo |
No direct in vivo activity has been reported for this compound alone. For PROTACs incorporating the BCP-based rigid linker, in vivo efficacy is evaluated in xenograft mouse models. The rigid, three-dimensional BCP scaffold can improve in vivo metabolic stability by reducing susceptibility to enzymatic degradation compared to linear alkyl or PEG linkers. BCP-containing PROTACs are typically administered via intraperitoneal or intravenous injection, and target protein degradation in tumor tissues is assessed by western blotting. The BCP scaffold may also enhance oral bioavailability due to its favorable physicochemical properties.
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| Enzyme Assay |
No specific enzyme/receptor binding protocols have been established for this compound. Standard synthetic protocols for using Methyl 3-(hydroxymethyl)bicyclo[1.1.1]pentane-1-carboxylate in PROTAC synthesis involve selective functionalization of the hydroxymethyl and ester groups. The methyl ester can be hydrolyzed using LiOH or NaOH in THF/water to yield the carboxylic acid, which can be activated with HATU or EDC for amide bond formation with amine-containing ligands. The hydroxymethyl group can be converted to a tosylate or mesylate for nucleophilic substitution, or oxidized to an aldehyde or carboxylic acid for reductive amination or amide coupling. Alternatively, the hydroxymethyl can be protected (e.g., as TBS ether) to allow selective ester hydrolysis first, followed by deprotection and conjugation. Products are purified by column chromatography or HPLC.
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| Cell Assay |
Methyl 3-(hydroxymethyl)bicyclo[1.1.1]pentane-1-carboxylate is not evaluated in cellular assays directly. For cellular evaluation of PROTACs synthesized using this BCP-based linker, standard protocols involve culturing cancer cell lines (e.g., HEK293, HeLa, MCF-7, or A549) in DMEM or RPMI-1640 with 10% FBS at 37degC in 5% CO2. Cells are seeded in 12- or 96-well plates at appropriate densities and allowed to attach overnight. PROTAC is added at concentrations ranging from 0.1 nM to 10 uM for 4-72 hours. Target protein degradation is assessed by western blotting of cell lysates using specific primary antibodies. Cell viability is measured using MTT or CellTiter-Glo assays. All conditions are tested in triplicate for statistical reliability. The rigid BCP linker may enable enhanced target degradation at lower concentrations compared to flexible linkers.
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| Animal Protocol |
For in vivo studies using PROTACs synthesized with this BCP-based linker, standard animal protocols involve xenograft models in immunodeficient mice (nude or NSG mice, 6-8 weeks old). Approximately 5×10⁶ cancer cells are injected subcutaneously. When tumors reach ~150-200 mm3, mice are randomized into treatment groups (n=5-10 per group). PROTAC is administered intraperitoneally or intravenously at doses of 1-50 mg/kg in formulation vehicles such as 10% DMSO, 40% PEG300, 5% Tween 80, 45% saline. Tumor volumes are measured every 2-3 days using digital calipers. Body weights are monitored as a toxicity indicator. At study termination, tumors are excised and processed for target protein analysis by western blotting. Blood may be collected for pharmacokinetic analysis.
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| ADME/Pharmacokinetics |
No direct pharmacokinetic studies have been published for Methyl 3-(hydroxymethyl)bicyclo[1.1.1]pentane-1-carboxylate. Computed properties include molecular formula C8H12O3, molecular weight 156.18 g/mol. The BCP scaffold has a predicted logP of approximately 0.5-1.0, indicating moderate water solubility. Compared to para-substituted benzene rings (typical logP ~2.0-2.5), the BCP scaffold is more polar and has a lower logP, which can improve aqueous solubility and reduce off-target hydrophobic interactions in PROTAC molecules. The BCP scaffold also provides a three-dimensional shape that can enhance target binding selectivity. For PROTACs incorporating this linker, pharmacokinetic properties are determined by the overall structure.
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| Toxicity/Toxicokinetics |
Safety data for Methyl 3-(hydroxymethyl)bicyclo[1.1.1]pentane-1-carboxylate indicates the compound is for research use only. Standard laboratory safety precautions should be followed: wear protective gloves, safety goggles, and a lab coat. Work in a well-ventilated fume hood. Avoid inhalation, ingestion, and contact with skin and eyes. The compound should be stored at -20degC, protected from light and moisture. While specific toxicity data is limited, the compound should be treated as potentially hazardous. This product is not for human therapeutic use.
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| Additional Infomation |
Methyl 3-(hydroxymethyl)bicyclo[1.1.1]pentane-1-carboxylate is a PROTAC linker featuring a bicyclo[1.1.1]pentane (BCP) core, a rigid, three-dimensional carbocyclic scaffold that serves as a bioisostere for para-substituted benzene rings, alkynes, and tert-butyl groups. The BCP scaffold is increasingly used in medicinal chemistry to replace flat aromatic rings with more conformationally constrained, three-dimensional structures, leading to improved metabolic stability, enhanced solubility, and reduced off-target binding. In PROTACs, rigid linkers like BCP can optimize ternary complex formation by providing defined spatial orientation between the target protein ligand and E3 ubiquitin ligase ligand, potentially enhancing degradation potency and selectivity. This product is for research use only and has no approved clinical applications.
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| Molecular Formula |
C8H12O3
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| Molecular Weight |
156.18
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| Exact Mass |
156.079
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| CAS # |
180464-87-3
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| PubChem CID |
10796998
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| Appearance |
Colorless to light yellow liquid（Density: 1.352±0.06 g/cm3）
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| Hydrogen Bond Donor Count |
1
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
11
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| Complexity |
190
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| Defined Atom Stereocenter Count |
0
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| SMILES |
COC(=O)C12CC(C1)(C2)CO
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| InChi Key |
BYTLJVZXUYVJKN-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C8H12O3/c1-11-6(10)8-2-7(3-8,4-8)5-9/h9H,2-5H2,1H3
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| Chemical Name |
methyl 3-(hydroxymethyl)bicyclo[1.1.1]pentane-1-carboxylate
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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 | 6.4029 mL | 32.0143 mL | 64.0287 mL | |
| 5 mM | 1.2806 mL | 6.4029 mL | 12.8057 mL | |
| 10 mM | 0.6403 mL | 3.2014 mL | 6.4029 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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