2. PROTAC
  3. Ligands for E3 Ligase
  4. VH-298

VH-298 is a highly potent inhibitor of the VHL:HIF-α interaction with a Kd value of 80 to 90 nM, used in PROTAC technology.

For research use only. We do not sell to patients.

VH-298 Chemical Structure

VH-298 Chemical Structure

CAS No. : 2097381-85-4

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10 mM * 1 mL in DMSO
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Customer Review

Based on 9 publication(s) in Google Scholar

Other Forms of VH-298:

VH-298 Related Antibodies

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von Hippel-Lindau (VHL) MDM2 Cereblon IAP

  • Biological Activity

  • Protocol

  • Purity & Documentation

  • References

  • Customer Review

Description

VH-298 is a highly potent inhibitor of the VHL:HIF-α interaction with a Kd value of 80 to 90 nM, used in PROTAC technology.

IC50 & Target

Kd: 80 to 90 nM (VHL:HIF-α)[1]
In Vitro

VH-298 is a potent, cell permeable and non-toxic chemical probe that triggers the hypoxic response by blocking the VHL. VH-298 is a highly potent inhibitor of the VHL:HIF-α interaction with Kd values of 90  and 80 nM in isothermal titration calorimetry and competitive fluorescence polarization assay. VH-298 binds with VHL complex very fast and dissociates slowly. VH-298 at 50 μM concentration exhibits negligible off-target effects in vitro against more than 100 tested cellular kinases, GPCRs and ion channels. VH-298 is cell permeable and not toxic to cells. The measured permeability of VH-298 is found to be 19.4 nm s -1. VH-298 induces concentration- and time-dependent on-target specific accumulation of hydroxylated HIF-α in human cell lines, including HeLa cancer cells and renal cell carcinoma 4 (RCC4) cells. VH-298 increases mRNA levels of EPO by 2.5-fold in RCC4-HA-VHL, but not in VHL-null RCC4-HA, indicating that pharmacological inhibition of VHL is able to stimulate endogenous EPO synthesis. VH-298 proves as effective as hypoxia in raising PHD2 and HK2 protein levels, however in HFF the BNIP3 protein level increases more with VH-298 treatment than hypoxia treatment[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

VH-298 Related Antibodies
Molecular Weight

523.65

Formula

C27H33N5O4S
CAS No.
Appearance

Solid

Color

Off-white to pink

SMILES

O=C([C@H]1N(C([C@H](C(C)(C)C)NC(C2(CC2)C#N)=O)=O)C[C@H](O)C1)NCC3=CC=C(C4=C(C)N=CS4)C=C3
Shipping

Room temperature in continental US; may vary elsewhere.
Storage
Powder -20°C 3 years
4°C 2 years
In solvent -80°C 6 months
-20°C 1 month
Solvent & Solubility
In Vitro: 

DMSO : ≥ 83.3 mg/mL (159.08 mM; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

*"≥" means soluble, but saturation unknown.

Preparing
Stock Solutions
Concentration Solvent Mass 1 mg 5 mg 10 mg
1 mM 1.9097 mL 9.5484 mL 19.0967 mL
5 mM 0.3819 mL 1.9097 mL 3.8193 mL
View the Complete Stock Solution Preparation Table

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

  • Molarity Calculator

  • Dilution Calculator

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

Mass
=
Concentration
×
Volume
×
Molecular Weight *

Concentration (start) × Volume (start) = Concentration (final) × Volume (final)

This equation is commonly abbreviated as: C1V1 = C2V2

Concentration (start)

C1

×
Volume (start)

V1

=
Concentration (final)

C2

×
Volume (final)

V2

In Vivo:

Select the appropriate dissolution method based on your experimental animal and administration route.

For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for in vivo experiments, it is recommended to prepare freshly and use it on the same day.
The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

  • Protocol 1

    Add each solvent one by one:  10% DMSO    40% PEG300    5% Tween-80    45% Saline

    Solubility: ≥ 2.5 mg/mL (4.77 mM); Clear solution

    This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).

    Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.

    Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
  • Protocol 2

    Add each solvent one by one:  10% DMSO    90% (20% SBE-β-CD in Saline)

    Solubility: ≥ 2.5 mg/mL (4.77 mM); Clear solution

    This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).

    Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.

    Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
In Vivo Dissolution Calculator
Please enter the basic information of animal experiments:

Dosage

mg/kg

Animal weight
(per animal)

g

Dosing volume
(per animal)

μL

Number of animals

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
%
DMSO +
% 
+
%
Tween-80 +
%
Saline
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Calculation results:
Working solution concentration: mg/mL
Method for preparing stock solution: mg drug dissolved in μL  DMSO (Stock solution concentration: mg/mL).
The concentration of the stock solution you require exceeds the measured solubility. The following solution is for reference only. If necessary, please contact MedChemExpress (MCE).
Method for preparing in vivo working solution for animal experiments: Take μL DMSO stock solution, add μL . μL , mix evenly, next add μL Tween 80, mix evenly, then add μL Saline.
 If the continuous dosing period exceeds half a month, please choose this protocol carefully.
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
Purity & Documentation

Purity: 99.78%

COA (249 KB) LCMS (136 KB)

Handling Instructions (2659 KB)
References
Kinase Assay
[1]

VH-298 is screened at 50 μM concentration against a panel of 50 kinases. The remaining kinase activity is recorded in the end of the assay. The data is reported as average % activity remaining of assay duplicates for each kinase tested[1].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Cell Assay
[1]

Death of CTLs is analyzed by staining with 4′,6-diamidino-2-phenylindole (DAPI). Cells are plated in 96-well plates at 1×106 and treated with VHL inhibitors (VH-298) and respective non-binding cis-analogues for 24 h. Cells are spun down and resuspended in HBSS containing DAPI to identify dead and dying populations[1].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.
References

Complete Stock Solution Preparation Table

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

Optional Solvent Concentration Solvent Mass 1 mg 5 mg 10 mg 25 mg
DMSO 1 mM 1.9097 mL 9.5484 mL 19.0967 mL 47.7418 mL
5 mM 0.3819 mL 1.9097 mL 3.8193 mL 9.5484 mL
10 mM 0.1910 mL 0.9548 mL 1.9097 mL 4.7742 mL
15 mM 0.1273 mL 0.6366 mL 1.2731 mL 3.1828 mL
20 mM 0.0955 mL 0.4774 mL 0.9548 mL 2.3871 mL
25 mM 0.0764 mL 0.3819 mL 0.7639 mL 1.9097 mL
30 mM 0.0637 mL 0.3183 mL 0.6366 mL 1.5914 mL
40 mM 0.0477 mL 0.2387 mL 0.4774 mL 1.1935 mL
50 mM 0.0382 mL 0.1910 mL 0.3819 mL 0.9548 mL
60 mM 0.0318 mL 0.1591 mL 0.3183 mL 0.7957 mL
80 mM 0.0239 mL 0.1194 mL 0.2387 mL 0.5968 mL
100 mM 0.0191 mL 0.0955 mL 0.1910 mL 0.4774 mL
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VH-298 Related Classifications

Help & FAQs
  • Do most proteins show cross-species activity?

    Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

Keywords:

VH-2982097381-85-4VH298VH 298Ligands for E3 LigaseE3 ligase-recruiting MoietyInhibitorinhibitorinhibit

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