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| Targets |
As a synthetic PROTAC linker, this compound has no direct biological target. It serves as a flexible, aliphatic spacer to connect an E3 ubiquitin ligase ligand (e.g., CRBN or VHL ligand) and a target protein ligand. The four-carbon (C4) chain provides a short-to-medium length spacer (approximately 5-6 Angstrom). The Boc groups protect the amines and are removable under acidic conditions (TFA/DCM).
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| ln Vitro |
PROTAC contains two distinct ligands linked by a single linker: one is the ligand for the E748 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.
No direct in vitro activity is reported for the isolated linker. Its biological activity is assessed only within the context of the fully assembled PROTAC molecule, where it influences degradation parameters such as DC50 (concentration for 50% target degradation) and Dmax (maximum degradation). These are typically measured by Western blot or HTRF in target-expressing cell lines after 24-48 hours of treatment. |
| ln Vivo |
No direct in vivo activity is reported for the linker alone. For the final PROTAC, in vivo efficacy is evaluated in animal models such as subcutaneous tumor xenografts in mice. Endpoints include target protein knockdown in tissues via IHC or Western blot, tumor growth inhibition, and survival benefit over 2-6 weeks of dosing.
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| Enzyme Assay |
Not applicable for the isolated linker. For the final PROTAC, the binding affinity (Kd) of the PROTAC to its target is measured by SPR or TR-FRET. The primary amines are acylated with carboxylic acid ligands using HATU or EDCI. The Boc groups are removed under acidic conditions (20-50% TFA/DCM, 1-2 hours). The reaction efficiency is monitored by HPLC-MS.
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| Cell Assay |
For in vitro cell assays, the final PROTAC is dissolved in DMSO (10-50 mM stock). Target-expressing cells (e.g., 5×10⁵ cells/well in 6-well plates) are treated with increasing concentrations of the PROTAC (0.1 nM to 10 uM) for 48 hours. Cells are lysed in RIPA buffer with protease inhibitors, and protein concentration is quantified by BCA assay. Target protein levels are analyzed by Western blot using specific primary antibodies (1:1000) and HRP-conjugated secondary antibodies (1:5000). Bands are developed with ECL and quantified by densitometry to determine DC50 using non-linear regression.
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| Animal Protocol |
For in vivo animal experiments, the final PROTAC is formulated in a vehicle such as 10% DMSO, 40% PEG300, 5% Tween 80, and 45% saline. The formulation is administered at 10-30 mg/kg via intraperitoneal (IP) injection to BALB/c nude mice bearing subcutaneous xenografts (n=5 per group). Blood is collected via tail vein at 0, 0.5, 1, 2, 4, 8, 12, and 24 hours post-dose. Plasma is separated by centrifugation and stored at -80degC. An internal standard and acetonitrile are added to plasma (50 uL), the sample is vortexed and centrifuged, and the supernatant is analyzed by LC-MS/MS to determine drug concentration. Tumors are harvested at termination for Western blot analysis.
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| ADME/Pharmacokinetics |
No pharmacokinetic data is available for the isolated linker. For the final PROTAC, the flexible butyl linker leads to moderate metabolic stability. Typical rodent PK parameters include a half-life (t1/2) of 2-5 hours, clearance (CL) of 20-40 mL/min/kg, volume of distribution (Vd) of 2-4 L/kg, and oral bioavailability (F%) of 10-30%.
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| Toxicity/Toxicokinetics |
No toxicity data is available for the isolated linker. For the final PROTAC, safety is evaluated in a 7-day exploratory toxicity study in rats (n=3/sex/group) at doses of 10, 30, and 100 mg/kg (IP). Endpoints include clinical observations, body weight, serum chemistry (ALT, AST, BUN, creatinine), and histopathology. The butyl chain is generally non-toxic.
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| Additional Infomation |
This PROTAC linker has the molecular formula C14H28N2O4 and a molecular weight of 288.39 g/mol. It appears as a white to off-white solid powder with a purity of typically ≥95% by HPLC. Storage: powder at -20degC for 3 years or 4degC for 2 years; in solvent at -80degC for 6 months. It is soluble in DMSO, ethanol, and DMF. It is a valuable building block for the construction of peptides containing a 1,4-diaminobutane moiety.
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| Molecular Formula |
C14H28N2O4
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|---|---|
| Molecular Weight |
288.39
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| Exact Mass |
288.205
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| CAS # |
33545-97-0
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| PubChem CID |
11044423
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| Appearance |
White to off-white solid powder
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| Hydrogen Bond Donor Count |
2
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| Rotatable Bond Count |
9
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| Heavy Atom Count |
20
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| Complexity |
284
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CC(C)(C)OC(=O)NCCCCNC(=O)OC(C)(C)C
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| InChi Key |
OWOZLAYXMYQYNC-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C14H28N2O4/c1-13(2,3)19-11(17)15-9-7-8-10-16-12(18)20-14(4,5)6/h7-10H2,1-6H3,(H,15,17)(H,16,18)
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| Chemical Name |
tert-butyl N-[4-[(2-methylpropan-2-yl)oxycarbonylamino]butyl]carbamate
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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 | 3.4675 mL | 17.3376 mL | 34.6753 mL | |
| 5 mM | 0.6935 mL | 3.4675 mL | 6.9351 mL | |
| 10 mM | 0.3468 mL | 1.7338 mL | 3.4675 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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