WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 406134
Description: XAV-939 is a Tankyrase (TNKS) inhibitor with potential anticancer activity. XAV-939 antagonizes Wnt signaling via stimulation of β-catenin degradation and stabilization of axin. XAV-939 inhibits proliferation of the μ-catenin-dependent colon carcinoma cell line DLD-1. Promotes cardiomyogenic development in mesoderm progenitor cells.
MedKoo Cat#: 406134
Chemical Formula: C14H11F3N2OS
Exact Mass: 312.05442
Molecular Weight: 312.31
Elemental Analysis: C, 53.84; H, 3.55; F, 18.25; N, 8.97; O, 5.12; S, 10.27
Synonym: XAV939; XAV 939; XAV-939.
IUPAC/Chemical Name: 2-(4-(trifluoromethyl)phenyl)-7,8-dihydro-3H-thiopyrano[4,3-d]pyrimidin-4(5H)-one
InChi Key: KLGQSVMIPOVQAX-UHFFFAOYSA-N
InChi Code: 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)
SMILES Code: O=C1C(CSCC2)=C2N=C(C3=CC=C(C(F)(F)F)C=C3)N1
Appearance: White Solid powder
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, not in water
Shelf Life: >5 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
|Biological target:||XAV-939 (NVP-XAV939) selectively inhibits Wnt/β-catenin-mediated transcription through tankyrase1/2 inhibition with IC50 of 11 nM/4 nM in cell-free assays, regulates axin levels and does not affect CRE, NF-κB or TGF-β.|
|In vitro activity:||Calcification of human VIC cultures was induced by cultivation in an osteogenic medium and the effect of co-incubation with 1μM XAV-939 was monitored. Calcification was quantified when mineral deposits were visible in culture and was histologically verified by von Kossa or Alizarin red staining and by IR-spectroscopy. Protein expression of alkaline phosphatase, Axin, β-catenin and Sox9 were quantified by western blotting. In 58% of the VIC preparations, calcification was induced in an osteogenic culture medium and was accompanied by upregulation of alkaline phosphatase. The calcification induction was prevented by the XAV-939 co-treatment and the alkaline phosphatase upregulation was suppressed. As expected, Axin was upregulated, but the levels of active non-phospho-β-catenin were also enhanced. Sox9 was induced during XAV-939 treatment but apparently not as a result of downregulation of β-catenin signalling. XAV-939 was therefore able to prevent calcification of human VIC cultures, and XAV-939 treatment was accompanied by upregulation of active non-phospho-β-catenin. Although XAV-939 does not downregulate active β-catenin, treatment with XAV-939 results in Sox9 upregulation that may prevent the calcification process. Reference: PLoS One. 2018 Dec 7;13(12):e0208774. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/30532256/|
|In vivo activity:||Mice underwent destabilization of the medial meniscus surgery and were treated by intra-articular injection with XAV-939, a small-molecule inhibitor of Wnt/β-catenin signaling. Wnt/β-catenin signaling was highly activated in murine synovial fibroblasts as well as in OA-derived human synovial fibroblasts. XAV-939 ameliorated OA severity associated with reduced cartilage degeneration and synovitis in vivo. Wnt inhibition using XAV-939 attenuated the proliferation and type I collagen synthesis in synovial fibroblasts in vitro but did not affect human OA-derived chondrocyte proliferation. However, Wnt modulation increased COL2A1 and PRG4 transcripts, which are downregulated in chondrocytes in OA. I Reference: JCI Insight. 2018 Feb 8;3(3):e96308. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/29415892/|
|Solvent||Max Conc. mg/mL||Max Conc. mM|
The following data is based on the product molecular weight 312.31 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|
|In vitro protocol:||1. Dittfeld C, Reimann G, Mieting A, Büttner P, Jannasch A, Plötze K, Steiner G, Tugtekin SM, Matschke K. Treatment with XAV-939 prevents in vitro calcification of human valvular interstitial cells. PLoS One. 2018 Dec 7;13(12):e0208774. doi: 10.1371/journal.pone.0208774. PMID: 30532256; PMCID: PMC6286025. 2. Almasoud N, Binhamdan S, Younis G, Alaskar H, Alotaibi A, Manikandan M, Alfayez M, Kassem M, AlMuraikhi N. Tankyrase inhibitor XAV-939 enhances osteoblastogenesis and mineralization of human skeletal (mesenchymal) stem cells. Sci Rep. 2020 Oct 7;10(1):16746. doi: 10.1038/s41598-020-73439-9. Erratum in: Sci Rep. 2021 Feb 19;11(1):4559. PMID: 33028869; PMCID: PMC7541626.|
|In vivo protocol:||1. Lietman C, Wu B, Lechner S, Shinar A, Sehgal M, Rossomacha E, Datta P, Sharma A, Gandhi R, Kapoor M, Young PP. Inhibition of Wnt/β-catenin signaling ameliorates osteoarthritis in a murine model of experimental osteoarthritis. JCI Insight. 2018 Feb 8;3(3):e96308. doi: 10.1172/jci.insight.96308. PMID: 29415892; PMCID: PMC5821202.|
1: Distler A, Deloch L, Huang J, Dees C, Lin NY, Palumbo-Zerr K, Beyer C, Weidemann A, Distler O, Schett G, Distler JH. Inactivation of tankyrases reduces experimental fibrosis by inhibiting canonical Wnt signalling. Ann Rheum Dis. 2012 Nov 12. [Epub ahead of print] PubMed PMID: 23148305.