XAV939

Biological Activity

XAV939 is an inhibitor of Tankryases with IC50 values of 11 and 4nM for Tankyrase 1 and Tankyrase 2, respectively. It stimulates beta-catenin degradation by stabilizing axin, resulting in the inhibition of the canonical Wnt pathway. Wnt proteins act on a variety of stem cells that include neural, mammary and embryonic stem cells. XAV939 increases the protein levels of the axin-GSK3β complex and promotes the degradation of β-catenin in SW480 cells. In addition, XAV939 inhibits growth of DLD-1 cells, an APC-deficient colorectal cancer cell line.

Product Citations

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  Neural Plast. 2021 Apr 19;2021:6680192.

  The Wnt/ β-Catenin Pathway Regulated Cytokines for Pathological Neuropathic Pain in Chronic Compression of Dorsal Root Ganglion Model
  XAV939 purchased from AbMole

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  Cell Communication & Signaling. 2020 Sep 10.

  JARID1B promotes colorectal cancer proliferation and Wnt/β-catenin signaling via decreasing CDX2 level
  XAV939 purchased from AbMole

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  Pharmacol Res. 2020 Jul;157:104831.

  Astragaloside IV acts through multi-scale mechanisms to effectively reduce diabetic nephropathy
  XAV939 purchased from AbMole

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  EBioMedicine. 2020 Jan 14.

  Systematic Investigation on Multi-Scale Mechanisms of Astragaloside IV in Treating Diabetic Nephropathy
  XAV939 purchased from AbMole

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  Stem Cell Res. 2020 Mar;43:101698.

  Cryopreservation of human pluripotent stem cell-derived cardiomyocytes is not detrimental to their molecular and functional properties.
  XAV939 purchased from AbMole

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  Eur Rev Med Pharmacol Sci. 2017 Apr;21(8):1980-1989.

  Isoflurane and sevoflurane affects Wnt/β-catenin signaling pathways in hippocampal formation of neonatal rats
  XAV939 purchased from AbMole

Customer Product Validations & Biological Datas

	Source	Customer experimental result (2019 Jan). XAV939 obtained from AbMole
	Method	treat liver in regeneration
	Cell Lines
	Concentrations	50uM
	Incubation Time	-
	Results	XAV939 treat liver in regeneration

	Source	Eur Med Pharmacol Sci (2017). XVA 939, Figure 4. (AbMole BioScience)
	Method
	Cell Lines
	Concentrations	2 mg/ml
	Incubation Time	30 min
	Results	Wnt inhibitor XAV 939 was significantly inhibited the up-regulation of Wnt and phosphorylated-β-catenin and increased phosphorylated-GSK-3β expression in the hippocampus in ISA and SEA groups, as compared with the control group at 5 weeks (Figure 4 A, B, C, p < 0.05).

	Source	Eur Med Pharmacol Sci (2017). XVA 939, Figure 3. (AbMole BioScience)
	Method
	Cell Lines
	Concentrations	2 mg/ml
	Incubation Time	30 min
	Results	As shown in Figure 3, the expression levels of Wnt3a and β-catenin (Figure 3A, C, p < 0.05) were significantly reduced after Wnt inhibitor XAV 939 treatment, while GSK-3β expression level was dramatically increased in ISAI and SEAI groups (Figure 3B, p < 0.05).

	Source	Eur Med Pharmacol Sci (2017). XVA 939, Figure 2. (AbMole BioScience)
	Method
	Cell Lines
	Concentrations	2 mg/ml
	Incubation Time	30 min
	Results	P7 rats treated with Wnt inhibitor XAV 939 could markedly relief that damage. Those morphological changes were significantly moderated and reduced neuronal loss at 10-week (Figure 2).

	Source	Eur Med Pharmacol Sci (2017). XVA 939, Figure 1. (AbMole BioScience)
	Method
	Cell Lines
	Concentrations	2 mg/ml
	Incubation Time	30 min
	Results	When rats were treated with Wnt inhibitor XAV 939 at 30 min before anesthesia, the impairment of brain could relieve. These findings suggested that impairment of learning and memory in P7 rats may through the Wnt signaling pathway.

Protocol

Cell Experiment
Cell lines	B-T549, MDA-MB-231, HCC-1143 and HCC-1937 cell lines
Preparation method	Cell viability assay. Cells were seeded at 20,000 cells/well into 96-well plates. After overnight incubation, cells were treated with DMSO or each Wnt inhibitor (iCRT-3, 75 μM; iCRT-5, 200 μM; iCRT-14, 50 μM; IWP-4, 5 μM and XAV-939, 10 μM) for 48 hours. Cell viability was determined using the Cell Titer-Glo luminescent cell viability assay kit (Promega) according to the manufacturer’s instructions. Luminescence was measured using FLUOstar microplate reader. All treatments were performed in triplicate, and each experiment was repeated three times.
Concentrations	10 μM
Incubation time	48 hr

Animal Experiment
Animal models	bleomycin-induced dermal fibcrosis mice model
Formulation	10% DMSO / 90% normal saline
Dosages	2.5 mg/kg, four times a day
Administration	Intraperitoneal injection

Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)

Species	Mouse	Rat	Rabbit	Guinea pig	Hamster	Dog
Weight (kg)	0.02	0.15	1.8	0.4	0.08	10
Body Surface Area (m2)	0.007	0.025	0.15	0.05	0.02	0.5
Km factor	3	6	12	8	5	20

Animal A (mg/kg) = Animal B (mg/kg) multiplied by	Animal B Km
	Animal A Km

For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the K_m factor for a mouse and then divide by the K_m factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.

Chemical Information

References

Wnt signaling blockage inhibits cell proliferation and migration, and induces apoptosis in triple-negative breast cancer cells.
Bilir B, et al. J Transl Med. 2013 Nov 4;11:280. PMID: 24188694.

Inactivation of tankyrases reduces experimental fibrosis by inhibiting canonical Wnt signalling.
Distler A, et al. Ann Rheum Dis. 2013 Sep 1;72(9):1575-80. PMID: 23148305.