| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 50mg |
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| 100mg |
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| Other Sizes |
| Targets |
VHL[1]
Von Hippel-Lindau (VHL) E3 ligase as a weak or non-binding ligand depending on stereochemistry. |
|---|---|
| ln Vitro |
(R,S,S)-VH032 is the (R,S,S) diastereomer of the well-characterized VHL ligand VH032 (which is typically (S,R,S) or (S,S,S) depending on nomenclature). This stereoisomer has significantly reduced binding affinity to VHL (Kd > 100 uM or no measurable binding) compared to the active stereoisomer (Kd ~0.1-1 uM). It is used as an inactive control in PROTAC experiments to confirm that degradation requires VHL engagement.
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| ln Vivo |
In vivo, (R,S,S)-VH032 does not induce target protein degradation when incorporated into PROTACs because it cannot recruit VHL. It serves as an important negative control to rule off-target degradation mechanisms. In xenograft models, PROTACs with the inactive stereoisomer show no tumor growth inhibition, confirming that activity depends on VHL binding.
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| Enzyme Assay |
VHL binding is measured by TR-FRET or SPR. (R,S,S)-VH032 (0-500 uM) is tested for competition with a fluorescent HIF-1alpha peptide bound to VHL complex. The inactive epimer shows no displacement (IC50 > 500 uM) or only weak displacement at high concentrations. This confirms loss of affinity due to incorrect stereochemistry.
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| Cell Assay |
Cells are treated with a PROTAC containing (R,S,S)-VH032 (0.1-10 uM) for 24 hours. Target protein levels are assessed by Western blot. The inactive PROTAC should not degrade the target, while the active (correct stereoisomer) PROTAC degrades efficiently. This control distinguishes specific VHL-mediated degradation from non-specific proteolysis.
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| Animal Protocol |
In vivo, mice bearing xenografts are treated with either the active PROTAC or the inactive (R,S,S)-VH032-containing PROTAC (10-50 mg/kg, IV). Tumors are collected for target degradation analysis. The inactive control shows no target degradation or tumor growth inhibition, confirming on-target mechanism. The compound is not used alone but as part of a PROTAC.
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| ADME/Pharmacokinetics |
Molecular weight: approximately 550-600 g/mol for VH032 free base. The (R,S,S) isomer has identical molecular formula and mass as the active isomer, differing only in stereochemistry. It has similar physicochemical properties (solubility, logP) but lacks biological activity. The compound is stable at -20degC.
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| Toxicity/Toxicokinetics |
(R,S,S)-VH032 has low toxicity (LD50 > 1000 mg/kg) based on VHL ligand data. As an inactive control, it is not expected to cause adverse effects at typical doses. Standard safety precautions apply. The compound is for research use only. No teratogenicity data specific to this epimer. Handle with general PPE.
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| References | |
| Additional Infomation |
(R,S,S)-VH032 is a critical negative control for PROTAC experiments. The three chiral centers in VH032 produce multiple diastereomers; only the (S,R,S) (or (2S,4R) depending on numbering) isomer binds VHL with high affinity. The (R,S,S) isomer is often used to verify that phenotypic effects of a PROTAC are due to VHL-mediated degradation. This compound is a research tool, not a drug candidate. No clinical approval.
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| Molecular Formula |
C22H30N4O3S
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|---|---|
| Molecular Weight |
430.563603878021
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| Exact Mass |
430.203
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| CAS # |
2230826-33-0
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| PubChem CID |
135157027
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| Appearance |
White to off-white solid powder
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| LogP |
2.1
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
30
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| Complexity |
618
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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)N)O
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| InChi Key |
ZLOXMSNKPDWMEF-YQVWRLOYSA-N
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| InChi Code |
InChI=1S/C22H30N4O3S/c1-13-18(30-12-25-13)15-7-5-14(6-8-15)10-24-20(28)17-9-16(27)11-26(17)21(29)19(23)22(2,3)4/h5-8,12,16-17,19,27H,9-11,23H2,1-4H3,(H,24,28)/t16-,17+,19+/m0/s1
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| Chemical Name |
(2R,4S)-1-[(2S)-2-amino-3,3-dimethylbutanoyl]-4-hydroxy-N-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]pyrrolidine-2-carboxamide
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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 | 2.3226 mL | 11.6128 mL | 23.2256 mL | |
| 5 mM | 0.4645 mL | 2.3226 mL | 4.6451 mL | |
| 10 mM | 0.2323 mL | 1.1613 mL | 2.3226 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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