Related CAS #
1428338-79-7 (RR-isomer)
1428339-47-2 (free base)
Synonym
V-11-0711; V11-0711; V 11-0711; V-110711; V110711; V 110711; V-11-0711 HCl;
IUPAC/Chemical Name
(S)-1-phenyl-1-((R)-quinuclidin-3-yl)-3-(2-((tetrahydro-2H-pyran-4-yl)oxy)phenyl)propan-1-ol hydrochloride
InChi Key
MPCSYCIXOHJVAI-JDAAGFJYSA-N
InChi Code
InChI=1S/C27H35NO3.ClH/c29-27(23-7-2-1-3-8-23,25-20-28-16-11-21(25)12-17-28)15-10-22-6-4-5-9-26(22)31-24-13-18-30-19-14-24;/h1-9,21,24-25,29H,10-20H2;1H/t25-,27+;/m0./s1
SMILES Code
O[C@@](C1=CC=CC=C1)(CCC2=C(OC3CCOCC3)C=CC=C2)[C@@]4(C5CCN(C4)CC5)[H].[H]Cl
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO
Shelf Life
>2 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
More Info
Phosphatidylcholine (PtdCho) has important roles in membrane structure and cell signaling. Increased levels of choline kinase (Chk)-α, the enzyme that converts choline to phosphocholine (PC) in the PtdCho biosynthesis, and PC are consistently observed in aggressive cancers including breast cancer [1-3]. Understanding the roles of Chk-α in cancer can result in new therapies.
Biological target:
V-11-0711 is a Chk-α inhibitor.
In vitro activity:
In a translational approach, the CHKα-inhibitor V-11-0711 (Vertex Pharmaceuticals Incorporated) was applied on GBM cells and tested subsequent alterations in geno- and phenotype. V-11-0711 has been shown to specifically suppress CHKα catalytic activity in breast cancer and HeLa cells. GBM1 and JHH520 neurospheres were treated with DMSO, 0.1 μM V-11-0711 or 1 μM V-11-0711 for 48 h and metabolic extracts were analyzed by 1H NMR spectroscopy. As the PC signal at 3.22 ppm was highly reduced in the drug treated cells the ability of V-11-0711 to inhibit the enzymatic activity of CHKα in GBM cells was confirmed (Figure 7A). Additionally, V-11-0711 induced a dose dependent increase of CHKα protein in GBM1 but not in JHH520 cell line. Strikingly, treatment with 1 μM or 10 μM V-11-0711 for 48 h drastically reduced the cell viability of GBM1 and JHH520 cells (Figure8A) which we could associate with dose-dependent induction of apoptosis (Figure 8B). This confirms V-11-0711 as a potent CHKα and EMT inhibitor and suggests that the identified EMT-oncometabolic network may also be helpful to develop more tailored diagnostics monitoring the invasive properties of GBMs as well as surveilling the success of anti-EMT therapy.
Reference: Oncotarget. 2016 Nov 8; 7(45): 73414–73431. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5341988/
Preparing Stock Solutions
The following data is based on the
product
molecular weight
458.04
Batch specific molecular weights may vary
from batch to batch
due to the degree of hydration, which will
affect the solvent
volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass |
1 mg |
5 mg |
10 mg |
| 1 mM |
1.15 mL |
5.76 mL |
11.51 mL |
| 5 mM |
0.23 mL |
1.15 mL |
2.3 mL |
| 10 mM |
0.12 mL |
0.58 mL |
1.15 mL |
| 50 mM |
0.02 mL |
0.12 mL |
0.23 mL |
Formulation protocol:
1. Koch K, Hartmann R, Schröter F, Suwala AK, Maciaczyk D, Krüger AC, Willbold D, Kahlert UD, Maciaczyk J. Reciprocal regulation of the cholinic phenotype and epithelial-mesenchymal transition in glioblastoma cells. Oncotarget. 2016 Nov 8;7(45):73414-73431. doi: 10.18632/oncotarget.12337. PMID: 27705917; PMCID: PMC5341988. 2. Falcon SC, Hudson CS, Huang Y, Mortimore M, Golec JM, Charlton PA, Weber P, Sundaram H. A non-catalytic role of choline kinase alpha is important in promoting cancer cell survival. Oncogenesis. 2013;2(3):e38. doi: 10.1038/oncsis.2013.2. PMID: 25522435; PMCID: PMC3641355.
In vitro protocol:
1. Koch K, Hartmann R, Schröter F, Suwala AK, Maciaczyk D, Krüger AC, Willbold D, Kahlert UD, Maciaczyk J. Reciprocal regulation of the cholinic phenotype and epithelial-mesenchymal transition in glioblastoma cells. Oncotarget. 2016 Nov 8;7(45):73414-73431. doi: 10.18632/oncotarget.12337. PMID: 27705917; PMCID: PMC5341988. 2. Falcon SC, Hudson CS, Huang Y, Mortimore M, Golec JM, Charlton PA, Weber P, Sundaram H. A non-catalytic role of choline kinase alpha is important in promoting cancer cell survival. Oncogenesis. 2013;2(3):e38. doi: 10.1038/oncsis.2013.2. PMID: 25522435; PMCID: PMC3641355.
1: Koch K, Hartmann R, Schröter F, Suwala AK, Maciaczyk D, Krüger AC, Willbold D,
Kahlert UD, Maciaczyk J. Reciprocal regulation of the cholinic phenotype and
epithelial-mesenchymal transition in glioblastoma cells. Oncotarget. 2016 Nov
8;7(45):73414-73431. doi: 10.18632/oncotarget.12337. PubMed PMID: 27705917;
PubMed Central PMCID: PMC5341988.
2: Mori N, Wildes F, Kakkad S, Jacob D, Solaiyappan M, Glunde K, Bhujwalla ZM.
Choline kinase-α protein and phosphatidylcholine but not phosphocholine are
required for breast cancer cell survival. NMR Biomed. 2015 Dec;28(12):1697-706.
doi: 10.1002/nbm.3429. Epub 2015 Oct 27. PubMed PMID: 26503172.
3: Falcon SC, Hudson CS, Huang Y, Mortimore M, Golec JM, Charlton PA, Weber P,
Sundaram H. A non-catalytic role of choline kinase alpha is important in
promoting cancer cell survival. Oncogenesis. 2013;2:e38. PubMed PMID: 25522435;
PubMed Central PMCID: PMC3641355.
