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VH-298 is a potent VHL inhibitor that stabilizes HIF-α and elicits a hypoxic response via a different mechanism, that is the blockade of the VHL:HIF-α protein-protein interaction downstream of HIF-α hydroxylation by PHD enzymes. 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 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.
| Molecular Weight | 523.65 |
| Formula | C27H33N5O4S |
| CAS Number | 2097381-85-4 |
| Solubility (25°C) | DMSO: ≥ 50 mg/mL |
| Storage |
Powder -20°C 3 years ; 4°C 2 years In solvent -80°C 6 months ; -20°C 1 month |
| Related Ligand for E3 Ligase Products |
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| Pomalidomide
Pomalidomide is the third-generation immunomodulatory agent, functions through interacting with the E3 ligase cereblon and induces degradation of essential Ikaros transcription factors. Pomalidomide is a second generation immunomodulator, TNF-α inhibitor with IC50 of 13 nM. |
| Thalidomide
Thalidomide is a sedative and immunomodulator used to study the symptoms of many cancers, it has immunomodulatory, anti-inflammatory and anti-angiogenic cancer properties. Thalidomide inhibits cereblon (CRBN), a part of the cullin-4 E3 ubiquitin ligase complex CUL4-RBX1-DDB1, with a Kd of ∼250 nM. |
| VHL Ligand 1 hydrochloride
VHL Ligand 1 hydrochloride is the VH032-based VHL ligand used in the recruitment of the von Hippel-Lindau (VHL) protein. |
| E3 ligase Ligand 1
E3 ligase Ligand 1 (VHL ligand 2 hydrochloride; (S,R,S)-AHPC-Me hydrochloride) is the (S,R,S)-AHPC-based VHL ligand used in the recruitment of the von Hippel-Lindau (VHL) protein. |
| E3 ligase Ligand 2
E3 ligase Ligand 2 (Thalidomide-4-OH) is the Thalidomide-based Cereblon ligand used in the recruitment of CRBN protein, it can be connected to the ligand for protein by a linker to form PROTACs. |
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