2097381-85-4|VH-298|CsnPharm

CAS No.: 2097381-85-4

VH-298 Catalog No. CSN20606

Synonyms: VH-298

VH-298 is a highly affinity inhibitor of E3 ubiquitin ligase VHL inhibitor (Kd = 80-90 nM) which can block the interaction of VHL and HIF-α, thus initiating hypoxic response.

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400-920-2911

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实验方案

技术信息

生物活性

描述Von Hippel-Lindau syndrome (VHL) is a component of the protein complex that includes elongin B, elongin C, and cullin-2, and possesses ubiquitin ligase E3 activity. VHL can induces hypoxia inducible factor (HIF) ubiquitination and degradation. VH-298 is a potent inhibitor of the VHL with a K_d of 90 nM as determined by isothermal titration calorimetry and 80 nM in a competitive fluorescence polarization assay. In vitro, the measured permeability of VH298 was 19.4 nm/s, and 500 μM of VH-298 did not affect the viability of HCC, Hela, RCC4-HA, RCC40-HA-VHL, U2OS and CTL cell lines, suggesting that VH298 was permeable and not toxic to cells. Treatment with 1 – 250 μM VH-298 for 2 hour induced dose-dependent accumulation of HIF-1α levels in Hela cells. In addition, VH-298 induced detectable HIF activity at concentration of 10 μM. Treatment with 100 μM VH298 elicited a HIF-dependent hypoxic response in HFF, Hela, and U2OS lines^[3]. In addition, VH-298 promoted rat fibroblasts proliferation at concentration of 30 μM and 100 μM, while 10 μM and 200 μM had no significant effect on cell proliferation. Treatment with 20 μM VH-298 promoted the tubule formation of HUVECs, however, 100 μM and 200 μM of VH-298 disturbed the tubule formation of HUVECs. In vivo, administered 100 μL of 30 μM VH-298 via local injection every three days accelerated wound healing in Rats with DM^[4].
作用机制VH-298 stabilizes HIF-α and induces a hypoxic response to block VHL-HIFα interaction^[3].
参考文献

[1] Soares P, Gadd MS, et al. Group-based optimization of potent and cell-active inhibitors of the von Hippel-Lindau (VHL) E3 ubiquitin ligase: structure-activity relationships leading to the chemical probe (2S,4R)-1-((S)-2-(1-cyanocyclopropanecarboxamido)-3,3-dimethylbutanoyl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide (VH298). J Med Chem. 2017 Aug 30.
[2] Frost J, Galdeano C, et al. Potent and selective chemical probe of hypoxic signalling downstream of HIF-α hydroxylation via VHL inhibition. Nat Commun. 2016 Nov 4;7:13312.
[3] Frost J, Galdeano C, Soares P, Gadd MS, Grzes KM, Ellis L, Epemolu O, Shimamura S, Bantscheff M, Grandi P, Read KD, Cantrell DA, Rocha S, Ciulli A. Potent and selective chemical probe of hypoxic signalling downstream of HIF-α hydroxylation via VHL inhibition. Nat Commun. 2016 Nov 4;7:13312.
[4] Qiu S, Jia Y, Sun Y, Han P, Xu J, Wen G, Chai Y. Von Hippel-Lindau (VHL) Protein Antagonist VH298 Improves Wound Healing in Streptozotocin-Induced Hyperglycaemic Rats by Activating Hypoxia-Inducible Factor- (HIF-) 1 Signalling. J Diabetes Res. 2019 Feb 17;2019:1897174.

实验方案

计算器摩尔计算器总药量计算器工作液计算器
储存液制备
- 1 mg
- 5 mg
- 10 mg
- 1 mM
- 1.9097 mL
- 9.5484 mL
- 19.0968 mL
- 5 mM
- 0.3819 mL
- 1.9097 mL
- 3.8194 mL
- 10 mM
- 0.1910 mL
- 0.9548 mL
- 1.9097 mL

技术信息

CAS号

2097381-85-4

储存条件

粉末: Sealed in dry,2-8°C

液体: -20°C:3-6 月 -80°C:12月

分子式

C27H33N5O4S

运输

蓝冰

分子量

523.65

别名

VH-298

溶解度

DMSO	100.0 mg/mL (191.0 mM)
Water	Insoluble
Ethanol	100.0 mg/mL (191.0 mM)

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