| Size | Price | Stock | Qty |
|---|---|---|---|
| 100mg |
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| 250mg |
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| Other Sizes |
| Targets |
VHL
Von Hippel-Lindau (VHL) E3 ubiquitin ligase (as a ligand) and target proteins via PROTAC-mediated degradation. |
|---|---|
| ln Vitro |
The (S,R,S)-AHPC moiety binds VHL with high affinity (Kd ~0.1-1 uM). The PEG5 spacer improves solubility and flexibility. The Boc (tert-butoxycarbonyl) group protects the terminal amine during synthesis; it is removed under acidic conditions to reveal a free amine for conjugation. The compound does not induce degradation alone. In PROTACs, it recruits VHL to ubiquitinate and degrade target proteins.
|
| ln Vivo |
PROTACs incorporating this VHL ligand have shown potent in vivo degradation of various oncoproteins (e.g., BRD4, BET, EGFR) in xenograft models. The PEG5 linker provides optimal pharmacokinetics with reduced clearance. The Boc protecting group is cleaved before conjugation; the free amine form is active for linker attachment. Specific in vivo data for the Boc-protected intermediate are not available.
|
| Enzyme Assay |
VHL binding is assessed by fluorescence polarization or ITC. Recombinant VHL-Elongin B-Elongin C complex is incubated with a fluorescent Hypoxia-inducible factor 1alpha (HIF-1alpha) peptide and varying concentrations of (S,R,S)-AHPC-PEG5-Boc (0-100 uM). Displacement of the peptide indicates binding. IC50 is typically 50-200 nM for the AHPC core; PEG5 does not significantly reduce affinity.
|
| Cell Assay |
In cellular assays, the compound itself does not degrade targets. For testing, the Boc is removed and the free amine is conjugated to a target warhead. The resulting PROTAC is incubated with cells (1-1000 nM) for 6-24 hours. Target degradation is assessed by Western blot. The intermediate serves as a negative control for PEG linker effects. Cell viability is measured by MTT.
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| Animal Protocol |
PROTACs derived from this building block are administered to xenograft mice via IV or IP injection (10-100 mg/kg). Tumor tissue is collected to assess target degradation. Blood samples are taken for PK analysis. The Boc-protected intermediate is not dosed directly. The free amine form is used for conjugation, and the final PROTAC is evaluated.
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| ADME/Pharmacokinetics |
Molecular weight: approximately 850-950 g/mol depending on exact structure. The PEG5 chain (MW ~220) confers water solubility. The Boc group is stable at room temperature but cleaved by TFA or HCl. The compound is stored at -20degC. As a building block, its independent PK is not relevant; PK depends on the final PROTAC.
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| Toxicity/Toxicokinetics |
The AHPC moiety is well-tolerated in animal studies at doses up to 100 mg/kg. Boc-protected amines are generally non-toxic. The compound is for research use only. Standard PPE required. Avoid inhalation and skin contact. Based on VHL ligand safety data, no significant acute toxicity is expected (LD50 > 2000 mg/kg).
|
| References | |
| Additional Infomation |
(S,R,S)-AHPC-PEG5-Boc is a key PROTAC building block. The stereochemistry (S,R,S) refers to the chiral centers in the VHL ligand. AHPC is also known as VH032. The Boc group allows orthogonal protection during synthesis. After deprotection, the free amine can react with carboxylic acids, NHS esters, or isocyanates. This VHL-based system is an alternative to cereblon-based degraders. No clinical approval.
|
| Molecular Formula |
C40H62N4O11S
|
|---|---|
| Molecular Weight |
807.005490779877
|
| Exact Mass |
806.413
|
| CAS # |
2923734-82-9
|
| PubChem CID |
155819524
|
| Appearance |
Light yellow to yellow solid powder
|
| LogP |
2.3
|
| Hydrogen Bond Donor Count |
3
|
| Hydrogen Bond Acceptor Count |
13
|
| Rotatable Bond Count |
27
|
| Heavy Atom Count |
56
|
| Complexity |
1190
|
| Defined Atom Stereocenter Count |
3
|
| 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)CCOCCOCCOCCOCCOCCC(=O)OC(C)(C)C)O
|
| InChi Key |
JVGJQSZGDYFSKY-FFTPJAJHSA-N
|
| InChi Code |
InChI=1S/C40H62N4O11S/c1-28-35(56-27-42-28)30-10-8-29(9-11-30)25-41-37(48)32-24-31(45)26-44(32)38(49)36(39(2,3)4)43-33(46)12-14-50-16-18-52-20-22-54-23-21-53-19-17-51-15-13-34(47)55-40(5,6)7/h8-11,27,31-32,36,45H,12-26H2,1-7H3,(H,41,48)(H,43,46)/t31-,32+,36-/m1/s1
|
| Chemical Name |
tert-butyl 3-[2-[2-[2-[2-[3-[[(2S)-1-[(2S,4R)-4-hydroxy-2-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methylcarbamoyl]pyrrolidin-1-yl]-3,3-dimethyl-1-oxobutan-2-yl]amino]-3-oxopropoxy]ethoxy]ethoxy]ethoxy]ethoxy]propanoate
|
| HS Tariff Code |
2934.99.9001
|
| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| 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 | 1.2391 mL | 6.1957 mL | 12.3914 mL | |
| 5 mM | 0.2478 mL | 1.2391 mL | 2.4783 mL | |
| 10 mM | 0.1239 mL | 0.6196 mL | 1.2391 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.
Products are for research use only; We do not sell to patients
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