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VR23
本产品不向个人销售,仅用作科学研究,不用于任何人体实验及非科研性质的动物实验。
VR23图片
CAS NO:1624602-30-7
规格:≥98%
包装与价格:
包装价格(元)
5mg电议
10mg电议
25mg电议
50mg电议
100mg电议
250mg电议
500mg电议

产品介绍
VR23 (VR-23; VR 23) is a highly potent and selective inhibitor of trypsin-like proteasome with potential antitumor activity. It inhibits trypsin-like, chymotrypsin-like, and caspase-like proteasomes with IC50s of 1 nM, 50-100 nM, and 3 μM, respectively. VR23 exhibits excellent in vivo antitumor efficacy in ATH490 athymic mice engrafted with MDA-MB-231 or RPMI 8226 cancer cells.
理化性质和储存条件
Molecular Weight (MW)477.88
FormulaC19H16ClN5O6S
CAS No.1624602-30-7
Storage-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)DMSO: 31 mg/mL (64.9 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
Other info

Chemical Name: 7-chloro-4-(4-((2,4-dinitrophenyl)sulfonyl)piperazin-1-yl)quinoline

InChi Key: PDQVZPPIHADUOO-UHFFFAOYSA-N

InChi Code: InChI=1S/C19H16ClN5O6S/c20-13-1-3-15-16(11-13)21-6-5-17(15)22-7-9-23(10-8-22)32(30,31)19-4-2-14(24(26)27)12-18(19)25(28)29/h1-6,11-12H,7-10H2

SMILES Code: O=S(N1CCN(C2=CC=NC3=CC(Cl)=CC=C32)CC1)(C4=C(C=C(C=C4)[N+]([O-])=O)[N+]([O-])=O)=O

Synonyms

VR-23; VR 23; VR23;

实验参考方法
In Vitro

In vitro activity: In HeLa cells, VR23 induces ubiquitinated proteins accumulation. In RPMI 8226 and KAS 6 cells, VR23 inhibits cell growth with IC50 of 2.94 and 1.46 μM, respectively. VR23 is also equally effective on both bortezomib (BTZ)-sensitive and -resistant RPMI 8226 and ANBL6 cells cells. When used in combination of bortezomib in the cells above, VR23 shows synergistic effects on cell growth inhibition. In addition, VR23 selectively induces cancer cell apoptosis by causing the accumulation of ubiquitinated cyclin E.


Kinase Assay: Exponentially growing cells on a 96-well clustered plate are treated with different concentrations of drugs or left untreated (control) for 6 hours. Proteasomes extracted with 0.5% NP40 buffer are mixed with equal amounts of samples in 100 μL total volume, and then incubated with 25 μmol/L of fluorogenic substrates (LRR- specific for trypsin-like activity, LLE-specific for caspase-like activity, and SUVY-specific for chymotrypsin-like activity) in black-bottom 96-well plates at 37°C. Fluorescence is monitored every 5 minutes at the wavelength of 360 nm (excitation) and 480 nm (emission).


Cell Assay: Treatment with VR23 made cancer cells undergo an abnormal centrosome amplification cycle. This cycle was caused by the accumulation of ubiquitinated cyclin E. Bortezomib is clinically approved as a chymotrypsin-like proteasome inhibitor. VR23 in combinations with bortezomib, caused a synergistic effect in killing multiple myeloma cells. This synergistic effect was also effective to myeloma cells resistant to bortezomib.

In VivoIn ATH490 athymic mice engrafted with MDA-MB-231 metastatic breast cancer cells, VR23 (30mg/kg, i.p.) shows effective antitumor and antiangiogenic activities. VR23 also reduces adverse effects caused by paclitaxel in mice.
Animal model ATH490 athymic mice engrafted with MDA-MB-231 or RPMI 8226 cancer cells
Formulation & DosageDissolved in 10% DMSO, 12.5% Cremophor, 12.5% ethanol, and 65% saline based diluent; 30 mg/kg; i.p. administration
References

Cancer Res. 2015 Oct 1;75(19):4164-75

生物活性

VR23 preferentially kills cancer over noncancer cells. Cancer Res. 2015 Oct 1;75(19):4164-75.

Combination of VR23 and bortezomib (BTZ) shows synergistic effects. Cancer Res. 2015 Oct 1;75(19):4164-75.

Localization of cyclin E to centrosomes correlates with centrosome amplification. Cancer Res. 2015 Oct 1;75(19):4164-75.

Ablation of cyclin E suppresses VR23-induced centrosome amplification. Cancer Res. 2015 Oct 1;75(19):4164-75.

Ubiquitinated cyclin E is accumulated in amplified centrosomes. Cancer Res. 2015 Oct 1;75(19):4164-75.

VR23 shows anticancer and antiangiogenesis activities. Cancer Res. 2015 Oct 1;75(19):4164-75.