1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEVH-298Cat. No.: HY-100947CAS No.: 2097381-85-4分式: CHNOS分量: 523.65作靶點: Ligand for E3 Ligase作通路: PROTAC儲存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性數(shù)據(jù)體外實驗 DMSO : 83.3 mg/mL (159.08 mM)* means soluble, b

2、ut saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制備儲備液1 mM 1.9097 mL 9.5484 mL 19.0967 mL5 mM 0.3819 mL 1.9097 mL 3.8193 mL10 mM 0.1910 mL 0.9548 mL 1.9097 mL請根據(jù)產(chǎn)品在不同溶劑中的溶解度，選擇合適的溶劑配制儲備液，并請注意儲備液的保存式和期限。體內(nèi)實驗請根據(jù)您的實驗動物和給藥式選擇適當(dāng)?shù)娜芙獍?，配制前請先配制澄清的儲備液，再依次添加助溶?為保證實驗結(jié)果的可靠性，體內(nèi)實驗的作液，建議您現(xiàn)現(xiàn)配，當(dāng)天使；澄清的儲

3、備液可以根據(jù)儲存條件，適當(dāng)保存；以下溶劑前的百分 指該溶劑在您配制終溶液中的體積占)：1. 請依序添加每種溶劑： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (4.77 mM); Clear solution2. 請依序添加每種溶劑： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.5 mg/mL (4.77 mM); Clear solution3. 請依序添加每種溶劑： 10% DMSO 90% corn oil1/2 Master of Small Mol

4、ecules 您邊的抑制劑師www.MedChemESolubility: 2.5 mg/mL (4.77 mM); Clear solutionBIOLOGICAL ACTIVITY物活性 VH-298效的 VHL:HIF- 相互作抑制劑， Kd 值為80-90 nM。 VH-298可于 PROTAC 技術(shù)中。IC50 & Target Kd: 80 to 90 nM (VHL:HIF-) 1體外研究 VH-298 is a potent, cell permeable and non-toxic chemical probe that triggers the hypoxic respon

5、se byblocking the VHL. VH-298 is a highly potent inhibitor of the VHL:HIF- interaction with Kd values of 90 and80 nM in isothermal titration calorimetry and competitive fluorescence polarization assay. VH-298 binds withVHL complex very fast and dissociates slowly. VH-298 at 50M concentration exhibit

6、s negligible off-targeteffects in vitro against more than 100 tested cellular kinases, GPCRs and ion channels. VH-298 is cellpermeable and not toxic to cells. The measured permeability of VH-298 is found to be 19.4nms -1. VH-298induces concentration- and time-dependent on-target specific accumulatio

7、n of hydroxylated HIF- in humancell lines, including HeLa cancer cells and renal cell carcinoma 4 (RCC4) cells. VH-298 increases mRNAlevels of EPO by 2.5-fold in RCC4-HA-VHL, but not in VHL-null RCC4-HA, indicating that pharmacologicalinhibition of VHL is able to stimulate endogenous EPO synthesis.

8、VH-298 proves as effective as hypoxia inraising PHD2 and HK2 protein levels, however in HFF the BNIP3 protein level increases more with VH-298treatment than hypoxia treatment 1.PROTOCOLKinase Assay 1 VH-298 is screened at 50 M concentration against a panel of 50 kinases. The remaining kinase activit

9、y isrecorded in the end of the assay. The data is reported as average % activity remaining of assay duplicatesfor 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-

10、2-phenylindole (DAPI). Cells are plated in 96-wellplates at 1106 and treated with VHL inhibitors (VH-298) and respective non-binding cis-analogues for 24h.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.REFERENCES1. Frost J, et al. Potent and selective chemical probe of hypoxic signalling downstream of HIF- hydroxylation via VHL inhibition. NatCommun. 2016 Nov 4;7:13312.McePdfHeightCaution: Product has not been