| Size | Price | Stock | Qty |
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| 50mg |
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| 100mg |
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| Other Sizes |
| Targets |
VHL
VH 101, thiol targets the von-Hippel-Lindau (VHL) protein, which is a substrate recognition component of an E3 ubiquitin ligase complex. VHL is part of the CUL2-RBX1-ELOB-ELOC E3 ubiquitin ligase complex that is involved in the ubiquitination and proteasomal degradation of various substrate proteins, most notably hypoxia-inducible factor 1α (HIF-1α). By binding to VHL, this molecule can recruit the E3 ligase machinery to a protein of interest when conjugated to a target-binding ligand. This leads to the ubiquitination and subsequent degradation of the target protein via the proteasome. The thiol functional group allows for facile conjugation to target protein ligands through disulfide bond formation or other thiol-reactive chemistry. |
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| ln Vitro |
In vitro activity of VH 101, thiol is not characterized as a pharmacological agent, as it is a synthetic building block rather than a biologically active compound. Its primary in vitro application is in the chemical synthesis of PROTAC molecules. The compound is used in conjugation reactions to attach to target protein-binding ligands via the terminal thiol group. The resulting PROTACs are then tested in cell-based assays for their ability to induce degradation of specific target proteins. VH 101, thiol itself is not typically evaluated for biological activity, as it is a research tool for PROTAC synthesis. Its characterization typically involves analytical techniques such as HPLC, NMR, and mass spectrometry to confirm identity and purity.
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| ln Vivo |
In vivo activity is not applicable to VH 101, thiol, as the compound is a synthetic building block for PROTAC synthesis rather than a directly administered drug. The compound is not used in animal studies in its native form. Instead, the PROTAC molecules synthesized from VH 101, thiol may be evaluated in vivo for their ability to induce target protein degradation and exert therapeutic effects. However, the specific in vivo activity of VH 101, thiol itself has not been reported. The compound is intended for research use only and is not intended for human use. Its role is limited to the chemical synthesis of more complex molecules that may have biological activity.
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| Enzyme Assay |
In vitro enzyme or receptor binding assay protocols are not directly applicable to VH 101, thiol, as the compound is a synthetic intermediate rather than a pharmacologically active compound. However, the VHL-binding activity of the VHL ligand moiety could be assessed using binding assays. A standard protocol for assessing VHL binding would involve surface plasmon resonance (SPR) or isothermal titration calorimetry (ITC) using recombinant VHL protein and the compound as the analyte. Fluorescence polarization assays using fluorescently labeled VHL ligands and VHL protein can also be employed. However, these assays are typically performed on the final PROTAC molecules or on the parent VHL ligand rather than on the VH 101, thiol intermediate. The compound is primarily characterized by analytical techniques such as HPLC and NMR to confirm identity and purity.
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| Cell Assay |
In vitro cell-based assay protocols are not directly applicable to VH 101, thiol, as the compound is a synthetic building block rather than a biologically active compound. The compound is not typically tested in cell-based assays in its native form. Instead, the PROTAC molecules synthesized from VH 101, thiol are evaluated in cell-based assays for their ability to induce degradation of target proteins. A standard protocol for evaluating PROTAC activity would involve treating cells expressing the target protein with varying concentrations of the PROTAC (typically 0.1 nM to 10 μM) for 4-24 hours, followed by Western blot analysis to assess target protein levels. Cell viability, cell cycle, and apoptosis may also be assessed. However, these assays are performed on the final PROTAC molecules, not on VH 101, thiol itself.
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| Animal Protocol |
In vivo animal experimental protocols are not applicable to VH 101, thiol, as the compound is a synthetic building block rather than a directly administered drug. The compound is not used in animal studies in its native form. Instead, PROTAC molecules synthesized from VH 101, thiol may be evaluated in vivo for their ability to induce target protein degradation and exert therapeutic effects. A hypothetical protocol for evaluating a PROTAC in vivo would involve administering the PROTAC to tumor-bearing mice via oral gavage or intraperitoneal injection at doses determined from preliminary pharmacokinetic and tolerability studies. Endpoints would include tumor growth inhibition, assessment of target protein degradation in tumor tissues by Western blot or immunohistochemistry, and evaluation of pharmacokinetic parameters. However, these studies are performed on the final PROTAC molecules, not on VH 101, thiol.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties are not applicable to VH 101, thiol as a directly administered compound, as it is a synthetic building block rather than a drug. The compound is not intended for in vivo administration, and its PK properties have not been characterized. However, the compound has a molecular weight of 534.67, a calculated LogP of 2.2, and a tPSA of 141. It is typically soluble in DMSO (e.g., 10 mM). The thiol functional group may be susceptible to oxidation, and the compound should be stored under inert conditions to maintain stability. Specific PK parameters such as half-life, Cmax, AUC, bioavailability, volume of distribution, and clearance have not been reported. The compound is intended for research use only and is not intended for human use.
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| Toxicity/Toxicokinetics |
Toxicological data for VH 101, thiol are limited, as the compound is intended for research use only and has not undergone systematic toxicity testing. No acute toxicity (LD50), subchronic toxicity, genotoxicity, or reproductive toxicity studies have been reported specifically for this compound. Based on its structure as a small molecule with a thiol functional group, it may have potential for reactivity with biological molecules, but specific toxicity data are lacking. The compound is not intended for human use. Researchers should follow standard safety precautions when handling the compound, including working in a fume hood, wearing appropriate personal protective equipment, and avoiding inhalation, ingestion, or skin contact. The compound should be stored as a powder at -20°C for up to 3 years or in solvent at -80°C for up to 6 months.
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| References | |
| Additional Infomation |
VH 101, thiol is a research-grade compound that serves as a functionalized VHL ligand for PROTAC research and development. It incorporates an E3 ligase ligand with a terminal thiol group, ready for conjugation to a target protein ligand. The compound is also known as compound 20. It has not entered clinical trials and is not approved for any therapeutic indication. Its mechanism of action is indirect: when incorporated into PROTAC molecules, it enables recruitment of the VHL E3 ubiquitin ligase to target proteins, leading to their ubiquitination and proteasomal degradation. The compound is available exclusively for research purposes and is not intended for diagnostic, therapeutic, or human applications.
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| Molecular Formula |
C25H31FN4O4S2
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|---|---|
| Molecular Weight |
534.66644692421
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| Exact Mass |
534.177
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| CAS # |
2358775-81-0
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| PubChem CID |
164864607
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| Appearance |
White to off-white solid powder
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| LogP |
2.2
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
8
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| Heavy Atom Count |
36
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| Complexity |
850
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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)S)NC(=O)C4(CC4)F)O
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| InChi Key |
RCVHBJGYHDKFGZ-WSTZPKSXSA-N
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| InChi Code |
InChI=1S/C25H31FN4O4S2/c1-14-19(36-13-28-14)16-6-4-15(5-7-16)11-27-21(32)18-10-17(31)12-30(18)22(33)20(24(2,3)35)29-23(34)25(26)8-9-25/h4-7,13,17-18,20,31,35H,8-12H2,1-3H3,(H,27,32)(H,29,34)/t17-,18+,20-/m1/s1
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| Chemical Name |
(2S,4R)-1-[(2R)-2-[(1-fluorocyclopropanecarbonyl)amino]-3-methyl-3-sulfanylbutanoyl]-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) |
Typically soluble in DMSO (e.g. 10 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 | 1.8703 mL | 9.3516 mL | 18.7031 mL | |
| 5 mM | 0.3741 mL | 1.8703 mL | 3.7406 mL | |
| 10 mM | 0.1870 mL | 0.9352 mL | 1.8703 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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