| Size | Price | Stock | Qty |
|---|---|---|---|
| 50mg |
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| 100mg |
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| Other Sizes |
| Targets |
VHL
Von Hippel-Lindau (VHL) as a ligand. The bromine serves as a leaving group for nucleophilic substitution to attach target-binding warheads. |
|---|---|
| ln Vitro |
The (S,R,S)-AHPC-Me moiety binds VHL with high affinity (Kd ~0.1-1 uM). The N-methyl group may modulate solubility and conformation. The C10 alkyl chain provides a long hydrophobic spacer. The terminal bromine is a versatile functional group for SN2 reactions with thiols, amines, or other nucleophiles to conjugate target ligands. The compound does not degrade proteins alone.
|
| ln Vivo |
PROTACs assembled using this linker have shown in vivo degradation of various targets in xenograft models. The C10 alkyl chain confers increased hydrophobicity, which can enhance cell permeability but may reduce solubility. The N-methyl group may improve metabolic stability. Specific in vivo data for this intermediate alone are not available.
|
| Enzyme Assay |
VHL binding is measured by TR-FRET or SPR. Recombinant VHL complex is incubated with a labeled HIF-1alpha peptide and varying concentrations of (S,R,S)-AHPC-Me-C10-Br (0-100 uM). Displacement curves give IC50 values (typically 50-200 nM). The C10-Br and N-methyl groups do not abolish binding. Binding affinity is retained within 2-fold of unmodified AHPC.
|
| Cell Assay |
In cellular assays, the intermediate alone does not induce degradation. For activity testing, the bromine is used to conjugate a target warhead (e.g., via thioether bond with a cysteine-containing ligand). The resulting PROTAC is incubated with cells (1-1000 nM) for 6-24 hours. Target degradation is assessed by Western blot. The intermediate is used as a control.
|
| Animal Protocol |
PROTACs derived from this building block are administered to xenograft mice (10-100 mg/kg, IV or IP). Tumor tissues are analyzed for target degradation. The intermediate itself is not dosed. PK parameters (t1/2, AUC) depend on the final PROTAC. The C10 chain may increase plasma protein binding compared to shorter linkers.
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| ADME/Pharmacokinetics |
Molecular weight: approximately 750-850 g/mol. The bromine atom is reactive; the compound should be stored at -20degC, protected from light and moisture. The C10 alkyl chain is lipophilic (logP ~5), which may cause aggregation in aqueous buffers. The compound is soluble in DMSO and organic solvents.
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| Toxicity/Toxicokinetics |
The AHPC-based VHL ligands have low toxicity in animal studies (LD50 > 1000 mg/kg). The C10-Br alkylating agent may be irritating and potentially genotoxic due to the alkyl bromide moiety. Standard safety precautions: use fume hood, avoid inhalation and skin contact. Not for human use.
|
| References | |
| Additional Infomation |
This compound is a PROTAC building block. The (S,R,S)-AHPC (also called VH032) is a high-affinity VHL ligand. The N-methyl variant is less common but may improve cell permeability. The C10 alkyl chain provides a long, flexible spacer; terminal bromine is a good leaving group for conjugation. Alternative linkers use terminal azide or alkyne for click chemistry. No clinical approval.
|
| Molecular Formula |
C34H51BRN4O4S
|
|---|---|
| Molecular Weight |
691.762147188187
|
| Exact Mass |
690.281
|
| CAS # |
2836297-55-1
|
| PubChem CID |
145925668
|
| Appearance |
White to off-white solid powder
|
| LogP |
7.2
|
| Hydrogen Bond Donor Count |
3
|
| Hydrogen Bond Acceptor Count |
6
|
| Rotatable Bond Count |
17
|
| Heavy Atom Count |
44
|
| Complexity |
910
|
| Defined Atom Stereocenter Count |
4
|
| SMILES |
CC1=C(SC=N1)C2=CC=C(C=C2)[C@H](C)NC(=O)[C@@H]3C[C@H](CN3C(=O)[C@H](C(C)(C)C)NC(=O)CCCCCCCCCCBr)O
|
| InChi Key |
DYDLRAYTCZUFBG-GOGGMHKJSA-N
|
| InChi Code |
InChI=1S/C34H51BrN4O4S/c1-23(25-15-17-26(18-16-25)30-24(2)36-22-44-30)37-32(42)28-20-27(40)21-39(28)33(43)31(34(3,4)5)38-29(41)14-12-10-8-6-7-9-11-13-19-35/h15-18,22-23,27-28,31,40H,6-14,19-21H2,1-5H3,(H,37,42)(H,38,41)/t23-,27+,28-,31+/m0/s1
|
| Chemical Name |
(2S,4R)-1-[(2S)-2-(11-bromoundecanoylamino)-3,3-dimethylbutanoyl]-4-hydroxy-N-[(1S)-1-[4-(4-methyl-1,3-thiazol-5-yl)phenyl]ethyl]pyrrolidine-2-carboxamide
|
| 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, 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) |
DMSO :~100 mg/mL (~144.56 mM)
|
|---|---|
| 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 | 1.4456 mL | 7.2279 mL | 14.4559 mL | |
| 5 mM | 0.2891 mL | 1.4456 mL | 2.8912 mL | |
| 10 mM | 0.1446 mL | 0.7228 mL | 1.4456 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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