| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
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| 10mg |
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| 50mg |
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| Other Sizes |
| Targets |
VHL (von Hippel-Lindau), an E3 ubiquitin ligase.
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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[2].
As a VHL-binding ligand-linker conjugate, this compound itself has no intrinsic biological activity; its function is to recruit the VHL E3 ubiquitin ligase complex. The terminal primary amine is used to conjugate to a target protein ligand, and the resulting PROTAC can ubiquitinate and degrade the target protein via the proteasome. |
| ln Vivo |
No specific in vivo activity has been reported for this conjugate alone; its in vivo degradation activity is observed only when conjugated to a target protein ligand to form a complete PROTAC molecule. The in vivo efficacy of such a PROTAC is typically evaluated in animal models.
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| Enzyme Assay |
N/A; this compound is not assessed in isolated enzyme/receptor binding assays. Its quality is confirmed by analytical methods such as HPLC and NMR, with a standard purity of 98%. Its binding affinity to VHL is validated as part of a complete PROTAC construct using biophysical methods.
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| Cell Assay |
N/A; this conjugate is not tested alone in cell-based assays. In a typical protocol for a complete PROTAC, cells are treated with the compound for 4-24 hours. Target protein levels are then quantified by Western blotting or a degradation assay to determine the DC50 (half-maximal degradation concentration).
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| Animal Protocol |
N/A; no animal studies are performed with the ligand-linker conjugate alone. For in vivo studies of a final PROTAC, the molecule is formulated in a suitable vehicle (e.g., 10% DMSO, 40% PEG300, 5% Tween-80, 45% saline) and administered to animal models. Target engagement and efficacy are measured by protein knockdown and tumor growth inhibition.
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| ADME/Pharmacokinetics |
This dihydrochloride salt form enhances solubility. The compound has a molecular weight of 632.64, a molecular formula of C28H43Cl2N5O5S, and is typically stored as a solid powder at -20degC for up to 3 years or in a solvent at -80degC for 6 months. It is soluble in DMSO.
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| Toxicity/Toxicokinetics |
This product is for research use only and is not for human therapeutic or clinical applications. Standard chemical safety precautions should be observed during handling. The dihydrochloride salt is hygroscopic and should be stored in a dry, airtight container.
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| References | |
| Additional Infomation |
The inclusion of a phenol group in this conjugate offers a unique chemical handle for further modification or for use in solid-phase synthesis of PROTACs. The four-carbon alkyl linker (C4) provides a short, flexible spacer that can be optimal for certain target protein-E3 ligase pairs. This compound is an advanced tool for targeted protein degradation research.
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| Molecular Formula |
C28H43CL2N5O5S
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|---|---|
| Molecular Weight |
632.642524003983
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| Exact Mass |
631.236
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| CAS # |
2376990-26-8
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| PubChem CID |
145874877
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| Appearance |
White to off-white solid powder
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| Hydrogen Bond Donor Count |
6
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
12
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| Heavy Atom Count |
41
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| Complexity |
840
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| Defined Atom Stereocenter Count |
3
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| SMILES |
CC1=C(SC=N1)C2=CC(=C(C=C2)CNC(=O)[C@@H]3C[C@H](CN3C(=O)[C@H](C(C)(C)C)NC(=O)C)O)OCCCCN.Cl.Cl
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| InChi Key |
LDWASNPVOMODPJ-OTCWRJAQSA-N
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| InChi Code |
InChI=1S/C28H41N5O5S.2ClH/c1-17-24(39-16-31-17)19-8-9-20(23(12-19)38-11-7-6-10-29)14-30-26(36)22-13-21(35)15-33(22)27(37)25(28(3,4)5)32-18(2)34;;/h8-9,12,16,21-22,25,35H,6-7,10-11,13-15,29H2,1-5H3,(H,30,36)(H,32,34);2*1H/t21-,22+,25-;;/m1../s1
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| Chemical Name |
(2S,4R)-1-[(2S)-2-acetamido-3,3-dimethylbutanoyl]-N-[[2-(4-aminobutoxy)-4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]-4-hydroxypyrrolidine-2-carboxamide;dihydrochloride
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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 :~100 mg/mL (~158.07 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 | 1.5807 mL | 7.9034 mL | 15.8068 mL | |
| 5 mM | 0.3161 mL | 1.5807 mL | 3.1614 mL | |
| 10 mM | 0.1581 mL | 0.7903 mL | 1.5807 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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