| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| 10mg |
|
||
| 50mg |
|
||
| Other Sizes |
| Targets |
Von Hippel-Lindau (VHL) E3 ligase (as a ligand). The phenol group may enable additional hydrogen bonding or serve as a handle for further derivatization.
|
|---|---|
| ln Vitro |
The (S,R,S)-AHPC core binds VHL with high affinity (Kd ~0.1-1 uM). The phenol group is positioned to interact with the VHL binding pocket; it may enhance binding affinity through hydrogen bonding with His110. The C6-amine provides a flexible alkyl spacer for conjugation to target warheads. The dihydrochloride salt improves water solubility. The compound alone does not degrade proteins; it is a building block for PROTACs.
|
| ln Vivo |
PROTACs assembled using this building block have shown potent in vivo degradation of various targets (e.g., BRD4, BCR-ABL) in xenograft models. The C6 alkyl chain offers a hydrophobic spacer that can enhance cell permeability. The phenolic group may improve VHL binding. Specific in vivo data for this intermediate alone are not available.
|
| Enzyme Assay |
VHL binding is assessed by TR-FRET or SPR. Recombinant VHL-Elongin B-Elongin C complex is incubated with a fluorescent HIF-1alpha peptide and varying concentrations of the compound (0-100 uM). IC50 is typically 50-200 nM. The phenol-alkylC6-amine group does not disrupt binding; affinity is similar to unmodified AHPC.
|
| Cell Assay |
Cells (e.g., HEK293) are treated with the compound alone (1-100 uM) to assess non-specific effects. No target degradation occurs without conjugation. For PROTAC evaluation, the free amine is conjugated to a target warhead (e.g., via amide bond). The resulting PROTAC is tested at 1-1000 nM for degradation by Western blot. The intermediate is used as a negative control.
|
| Animal Protocol |
In vivo, PROTACs derived from this building block are dosed in xenograft mice (10-50 mg/kg, IV or IP). Tumor tissues are analyzed for target degradation. The intermediate alone is not administered. PK parameters of the final PROTAC are determined. The C6 chain may increase plasma protein binding.
|
| ADME/Pharmacokinetics |
Molecular weight: approximately 650-700 g/mol (free base) plus 2HCl. The dihydrochloride salt provides high aqueous solubility (>20 mg/mL). The C6 alkyl chain is lipophilic; the amine is protonated at pH 7.4. The phenolic group has pKa ~10. The compound is stored at -20degC, protected from light.
|
| Toxicity/Toxicokinetics |
The AHPC-based VHL ligands have low toxicity (LD50 > 1000 mg/kg). The dihydrochloride salt is non-toxic. The phenolic group may cause mild irritation. Standard safety precautions apply: avoid dust, use gloves. The compound is for research only. No teratogenicity data specifically for VHL ligands, but handle as potential reproductive toxin.
|
| References | |
| Additional Infomation |
This compound is a PROTAC building block. The (S,R,S)-AHPC (VH032) is a high-affinity VHL ligand. The phenol-alkylC6-amine variant is used to attach target warheads via the C6-amine. The phenolic group may be used for additional conjugation (e.g., via diazonium coupling). The dihydrochloride salt is the preferred form for storage and handling. This intermediate is a key reagent in the development of VHL-based degraders. No clinical approval.
|
| Molecular Formula |
C30H47CL2N5O5S
|
|---|---|
| Molecular Weight |
660.695684671402
|
| Exact Mass |
659.267
|
| CAS # |
2376990-28-0
|
| PubChem CID |
145874879
|
| Appearance |
Light yellow to yellow solid powder
|
| Hydrogen Bond Donor Count |
6
|
| Hydrogen Bond Acceptor Count |
8
|
| Rotatable Bond Count |
14
|
| Heavy Atom Count |
43
|
| Complexity |
871
|
| 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)C)O)OCCCCCCN.Cl.Cl
|
| InChi Key |
ZDPHPLMGGQWIRY-SGROTYDGSA-N
|
| InChi Code |
InChI=1S/C30H45N5O5S.2ClH/c1-19-26(41-18-33-19)21-10-11-22(25(14-21)40-13-9-7-6-8-12-31)16-32-28(38)24-15-23(37)17-35(24)29(39)27(30(3,4)5)34-20(2)36;;/h10-11,14,18,23-24,27,37H,6-9,12-13,15-17,31H2,1-5H3,(H,32,38)(H,34,36);2*1H/t23-,24+,27-;;/m1../s1
|
| Chemical Name |
(2S,4R)-1-[(2S)-2-acetamido-3,3-dimethylbutanoyl]-N-[[2-(6-aminohexoxy)-4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]-4-hydroxypyrrolidine-2-carboxamide;dihydrochloride
|
| 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) |
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
|
|---|---|
| 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 | 1.5135 mL | 7.5677 mL | 15.1355 mL | |
| 5 mM | 0.3027 mL | 1.5135 mL | 3.0271 mL | |
| 10 mM | 0.1514 mL | 0.7568 mL | 1.5135 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
Copyright 2020 InvivoChem LLC | All Rights Reserved
