2097381-85-4
2097381-85-4 structure
- Name: VH 298
- Chemical Name: VH-298
- CAS Number: 2097381-85-4
- Molecular Formula: C27H33N5O4S
- Molecular Weight: 523.65
- Catalog: Signaling Pathways PROTAC Ligand for E3 Ligase
- Create Date: 2018-03-31 23:08:13
- Modify Date: 2024-01-02 20:08:43
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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.
| Name | VH-298 |
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| 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. |
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| Related Catalog | |
| 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]. |
| Kinase Assay | 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]. |
| Cell Assay | 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]. |
| References |
| Molecular Formula | C27H33N5O4S |
|---|---|
| Molecular Weight | 523.65 |
| Storage condition | 2-8℃ |