2-[4-(trifluoromethyl)phenyl]-5H,7H,8H-thiopyrano[4,3-d]pyrimidin-4-ol

• ChemBase ID: 72563
• Molecular Formular: C14H11F3N2OS
• Molecular Mass: 312.3101496
• Monoisotopic Mass: 312.05441864
• SMILES: c1cc(ccc1C(F)(F)F)c1nc(c2c(n1)CCSC2)O
• Canonical SMILES: Oc1nc(nc2c1CSCC2)c1ccc(cc1)C(F)(F)F
• InChI: InChI=1S/C14H11F3N2OS/c15-14(16,17)9-3-1-8(2-4-9)12-18-11-5-6-21-7-10(11)13(20)19-12/h1-4H,5-7H2,(H,18,19,20)
• InChIKey: KLGQSVMIPOVQAX-UHFFFAOYSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: 2-[4-(trifluoromethyl)phenyl]-5H,7H,8H-thiopyrano[4,3-d]pyrimidin-4-ol
• IUPAC Traditional name: 2-[4-(trifluoromethyl)phenyl]-5H,7H,8H-thiopyrano[4,3-d]pyrimidin-4-ol
• Synonyms: XAV939; XAV-939

Database IDs

• CAS Number: 284028-89-3
• PubChem SID: 162037488
• PubChem CID: 2726824

CALCULATED PROPERTIES

• Acid pKa: 12.525094
• H Acceptors: 3
• H Donor: 1
• LogD (pH = 5.5): 4.43885
• LogD (pH = 7.4): 4.4388576
• Log P: 4.438861
• Molar Refractivity: 86.678 cm^3
• Polarizability: 28.26515 Å^3
• Polar Surface Area: 46.01 Å^2
• Rotatable Bonds: 2
• Lipinski's Rule of Five: true

PROPERTIES

Physical Property

• Solubility: DMSO

Safety Information

• Storage Condition: -20°C

Pharmacology Properties

• Target: Wnt

Product Information

• Salt Data: Free Base

DETAILS

Selleck Chemicals - S1180

Research Area

• Description: Cancer

Biological Activity

• Description: XAV-939 is a selective Wnt β-catenin-mediated transcription inhibitor for TNKS1 and TNKS2 with IC50 of 11 nM and 4 nM, respectively.
• Targets: TNKS1; TNKS2
• IC50: 11 nM; 4 nM ^[1]
• In Vitro: XAV-939 specifically inhibits tankyrase PARP activity. XAV-939 dramatically decreases DNA-PKcs protein levels, confirming the critical role of tankyrase poly-ADP-ribosylation activity in maintaining stability of the DNA-PKcs protein. The greatest reduction of DNA-PKcs protein levels (< 25%="" relative="" expression="" compared="" to="" dmso="" treated="" controls)="" occurs="" at="" 12="" hours="" with="" 1.0="" μm="" xav-939="" exposure.="" treatment="" of="" human="" lymphoblasts="" with="" 1.0="" μm="" xav-939="" results="" in="" marked="" elevation="" of="" tankyrase="" 1="" levels.="">^[1] XAV-939 is axin stabilizing agent. XAV-939 stimulates beta-catenin degradation by stabilizing axin, the concentration-limiting component of the destruction complex. XAV-939 stabilizes axin by blocking the poly-ADP-ribosylating enzymes tankyrase 1 and tankyrase 2. Both tankyrase isoforms interact with a highly conserved domain of axin and stimulate its degradation through the ubiquitin-proteasome pathway. XAV-939 deregulates the Wnt/b-catenin pathway which has been implicated in many cancers. ^[2]

Protocol

• Protocol: Cell Assay ^[1]
• Cell Lines: WTK1 lymphoblasts
• Concentrations: 1.0 μM
• Incubation Time: 8 hours
• Methods: XAV-939 is solubilized in DMSO at 55 °C to make a 10 mM stock solution which may be diluted later to a working concentration of 100 μM. WTK1 lymphoblasts treated with either DMSO or 1.0 μM XAV-939 for 8 hours are loaded into independent wells of a 4-20% gradient SDS-PAGE every 2 hours over the course of 6 hours. At each time point, DMSO and XAV-939 samples are loaded into wells immediately adjacent to the prior time point. The corresponding load times at 0, 2 and 4 hours results in total run times of 2, 4 and 6 hours respectively. The gel is analyzed via western blot for DNA-PKcs following completion of the final run time and is quantified after normalization to actin loading controls.

References

• References: [1] Dregalla RC, et al. Aging, 2010, 2(10), 691-708.
• References: [2] Huang SM, et al. Nature, 2009, 461(7264), 614-620.

REFERENCES

• Dregalla RC, et al. Aging, 2010, 2(10), 691-708.
• Huang SM, et al. Nature, 2009, 461(7264), 614-620.