product name VR23
Description: VR23 is a potent and selective proteasome inhibitor with IC50 of 1 nM, 50-100 nM, and 3 μM for trypsin-like proteasomes, chymotrypsin-like proteasomes, and caspase-like proteasomes, respectively. The primary molecular target of VR23 was β2 of the 20S proteasome catalytic subunit. Notably, VR23 was structurally distinct from other known proteasome inhibitors and selectively killed cancer cells by apoptosis, with little effect on noncancerous cells. VR23 was effective in vivo in controlling multiple myelomas and metastatic breast cancer cells, in the latter case also enhancing the antitumor activity of paclitaxel while reducing its side effects.
References: Cancer Res. 2015 Oct 1;75(19):4164-75.
477.88
Formula
C19H16ClN5O6S
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
Solubility (In vivo)
Synonyms
other peoduct :
| 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 Vivo | In 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 & Dosage | Dissolved 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 |
