For research use only. Not for therapeutic Use.
VR23（Cat No.:I002091）is a selective inhibitor of Rho-associated protein kinase (ROCK), a key regulator of the cytoskeleton and cellular motility. By inhibiting ROCK, VR23 disrupts processes such as cell migration, proliferation, and contraction, making it a valuable compound for studying cancer metastasis, cardiovascular diseases, and neurodegenerative disorders. ROCK inhibition by VR23 has been shown to promote apoptosis in certain cancer cells and improve vascular function in cardiovascular studies. This compound is essential for researchers exploring the therapeutic potential of ROCK inhibitors in various pathological conditions.
| Catalog Number | I002091 |
| CAS Number | 1624602-30-7 |
| Synonyms | 7-chloro-4-(4-((2,4-dinitrophenyl)sulfonyl)piperazin-1-yl)quinoline |
| Molecular Formula | C19H16ClN5O6S |
| Purity | ≥95% |
| Target | Proteasome |
| Solubility | 10 mM in DMSO (warmed) |
| Storage | Store at -20°C |
| IC50 | 1 nM (trypsin-like proteasome), 50-100 nM(chymotrypsin-like proteasome), 3 μM (caspase-like proteasome) |
| IUPAC Name | 7-chloro-4-[4-(2,4-dinitrophenyl)sulfonylpiperazin-1-yl]quinoline |
| InChI | 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 |
| InChIKey | PDQVZPPIHADUOO-UHFFFAOYSA-N |
| SMILES | C1CN(CCN1C2=C3C=CC(=CC3=NC=C2)Cl)S(=O)(=O)C4=C(C=C(C=C4)[N+](=O)[O-])[N+](=O)[O-] |
| Reference | 1:Cancer Res. 2015 Oct 1;75(19):4164-75. doi: 10.1158/0008-5472.CAN-14-3370. Epub 2015 Aug 3. VR23: A Quinoline-Sulfonyl Hybrid Proteasome Inhibitor That Selectively Kills Cancer via Cyclin E-Mediated Centrosome Amplification.Pundir S,Vu HY,Solomon VR,McClure R,Lee H, PMID: 26238784 DOI: 10.1158/0008-5472.CAN-14-3370 </br><span>Abstract:</span> The proteasome is clinically validated as a target for cancer therapeutics. However, proteasome-inhibitory agents that are cancer selective have yet to be developed. In this study, we report the identification of a safe and effective proteasome inhibitor with selective anticancer properties. We screened a chemical library constructed using a hybrid approach that incorporated a 4-piperazinylquinoline scaffold and a sulfonyl phamarcophore. From this library, we identified 7-chloro-4-(4-(2,4-dinitrophenylsulfonyl)piperazin-1-yl)quinoline (VR23) as a small molecule that potently inhibited the activities of trypsin-like proteasomes (IC50 = 1 nmol/L), chymotrypsin-like proteasomes (IC50 = 50-100 nmol/L), and caspase-like proteasomes (IC50 = 3 μmol/L). Data from molecular docking and substrate competition assays established that 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. Mechanistic investigations showed that cancer cells exposed to VR23 underwent an abnormal centrosome amplification cycle caused by the accumulation of ubiquitinated cyclin E. In combinations with the clinically approved chymotrypsin-like proteasome inhibitor bortezomib, VR23 produced a synergistic effect in killing multiple myeloma cells, including those that were resistant to bortezomib. 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. Overall, our results identify VR23 as a structurally novel proteasome inhibitor with desirable properties as an anticancer agent.©2015 American Association for Cancer Research. |
