VH 298

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

一种有效的、特异性细胞活性的 VHL E3 泛素连接酶抑制剂，可抑制 VHL/HIF-α 相互作用，在 ITC 测定中 Kd 为 90 nM。

A potent, specific cell-active VHL E3 ubiquitin ligase inhibitor that inhibits VHL/HIF-α interaction with Kd of 90 nM in ITC assays; selectively engages VHL as its prime cellular target and is not toxic to cells, induces concentration- and time-dependent on-target specific accumulation of hydroxylated HIF-α in human cell lines; induces HIF transcriptional activity and upregulates HIF-dependent response gene products, elicits a HIF-dependent hypoxic response in various cell lines.

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.

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VH298 | VH298

PROTACs

E3 Ligase Ligand

E3 Ligase Ligand

Metabolic Disease

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2097381-85-4

523.652

C27H33N5O4S

>98% (HPLC)

In Vitro:?DMSO : ≥ 83.3 mg/mL (159.08 m)

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

(2S,4R)-1-((S)-2-(1-Cyanocyclopropanecarboxamido)-3,3-dimethylbutanoyl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide

(-20℃)

With Ice Pack

≥ 2 years