XAV-939 化学構造
分子量: 312.31

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Quality Control & MSDS

製品説明

  • Compare Wnt/beta-catenin Inhibitors
    Wnt/beta-catenin製品生物活性の比較
  • 研究分野
  • XAV-939のメカニズム

製品の説明

生物活性

製品説明 XAV-939 は小分子選択阻害剤、Wnt通路転写因子β- catenin調節の転写を抑制、TNKS1 と TNKS2を作用すると、 IC50 がそれぞれ 11 nM 、 4 nMとなる.
ターゲット TNKS1 TNKS2
IC50 11 nM 4 nM [1]
In vitro試験 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]
Cell Data
Cell LinesAssay TypeConcentrationIncubation TimeFormulationActivity DescriptionPMID
Sf-21 MlnsT4lv[XOnIFHzd4F6 NYCxfmdDOThwN{Wg{txO NX\uOpJUPjBibXnu MnL0SG1UVw>? NFW3PWNKdmirYnn0bY9vKG:oIF6teIVzdWmwYXygS3NVNXSjZ3fl[EBVVkuVMjDlfJBz\XO|ZXSge4l1cCCLQ{WwJI9nKDBwMEC1N{DPxE1? MlvhNlM5Pzl2M{G=
HEK293T MVzGeY5kfGmxbjDBd5NigQ>? NIXJc3FFVVOR NXj3O45oUW6qaXLpeIlwdiCxZjDXcpQhe2mpbnHsbY5oKGG|c3Xzd4VlKGG|IHnubIljcXSrb36gc4Yh\m:{c3vvcIlvNWmwZIXj[YQh[0GPUDDy[ZNxd26|ZTDlcIVu\W62IHHjeIl3[XSrb36ge4l1cCCLQ{WwJI9nKDBwMEe4JO69VQ>? MmjhNlM5Pzl2M{G=
HEK293T Mlm4SpVv[3Srb36gRZN{[Xl? NFPqd5kyOCEQvF2= NYS5NowxTE2VTx?= NHf0R5ZKdmirYnn0bY9vKG:oIHLleIEu[2G|ZXnuMYRmeGWwZHXueEBk[W6xbnnjZYwhX262MzDwZZRpf2G7IIfpeIghUUN3MDDv[kAxNjB3MTFOwG0> NW[wPG45OjJzOUG1OVc>
HEK293T MUjGeY5kfGmxbjDBd5NigQ>? MV:yOEBp MVLEUXNQ M{LvdWlvcGmkaYTpc44hd2ZibX;1d4UhX262M1Ggd4lodmGuaX7nJJdqfGhiSVO1NEBw\iByLkC3PEDPxE1? NEDzVlIzOjJ4MEKwNy=>
SW480 MmfVSpVv[3Srb36gRZN{[Xl? NXnBVGRCOTBizszN NFPRT24zPCCq NEWyU3RFVVOR NHv6elZUfGGkaXzpfoF1cW:wIH;mJGF5cW5{IIfpeIghTUN3MDDv[kAxNjN5MTFOwG0> MXmyNlI3ODJyMx?=
HEK293T NFLJeGxHfW6ldHnvckBCe3OjeR?= NUXSPIhxPTBizszN NFPldYxFVVOR MWTIZZMhdm9iRX\m[YN1KG:wIH\vdpNsd2yrbj3pcoR2[2WmIHPBUXAhe2mpbnHsbY5oKGmwIHj1cYFvKEiHS{K5N3Qh[2WubIOgZ49mgHC{ZYPzbY5oKEOURR?= MWeyNlI3ODJyMx?=
IEC-6 MXrGeY5kfGmxbjDBd5NigQ>? M37leFYhcA>? NFPtT3BCdnSjZ3;ubZN1KGGldHn2bZR6KGG2IFLleIEu[2G2ZX7pck9VS0ZiYYPz[ZN{\WRiYYOgbY5pcWKrdHnvckBw\iCZboStN4EucW6mdXPl[EBigGmwMjDlfJBz\XO|aX;uJJdqfGhiSVO1NEBw\iByLk[0JO69VQ>? MXKyOFA3ODR6OR?=
IEC-6 MlHNSpVv[3Srb36gRZN{[Xl? MkLROkBp NETkcHBCdnSjZ3;ubZN1KGGldHn2bZR6KGG2IFLleIEu[2G2ZX7pck9VS0ZiYYPz[ZN{\WRiYYOgbY5pcWKrdHnvckBw\iCZboStN4EucW6mdXPl[EBt\3J3IHX4dJJme3Orb36ge4l1cCCLQ{WwJI9nKDJwOTFOwG0> NHmyVHIzPDB4MES4PS=>
DLD1 NGfxUXpHfW6ldHnvckBCe3OjeR?= NYHQXJZLOjBizszN NXvPOmgyOjRiaB?= MlHFSG1UVw>? NWnocHYzUW6qaXLpeIlwdiCxZjD0ZY5sgXKjc3WgZZN{\XO|ZXSgZZMhcW6qaXLpeIlwdiCxZjDUR2Yu\GWyZX7k[Y51KHS{YX7zZ5JqeHSrb37hcEBi[3Srdnn0fS=> MVmyOFUzPzd7Mh?=
DLD1 NWHidIZMS3m2b4TvfIlkKEG|c3H5 MUWyNEDPxE1? MlGzNVAh\A>? MmPFSG1UVw>? MXPDfZRwfG:6aXPpeJkh[XO|ZYPz[YQh[XNiZ4Lve5RpKGmwaHnibZRqd25? Mn3yNlQ2Ojd5OUK=
VERO MU\GeY5kfGmxbjDBd5NigQ>? M1rFXVI2KM7:TR?= NUnlSJdqTE2VTx?= MX\EbZN1fXKkZYOgVGFTKGKnbISgd5lvfGinc3nzMEBi\m[nY4TpcochfGinIHHjeIlvKGO7dH;zb4Vt\XSxbjygZ4VtdCC|aHHw[UBidmRiY3XscEBi\Ginc3nvci=> NX74W4NuOjV|M{K4OFU>
HeLa NU\uOVQ3TnWwY4Tpc44hSXO|YYm= MYixNEDPxE1? MX:0PEBp MULS[YR2[3Srb36gc4Yh[3m2b4DsZZNucWNiZHnzeJJq[nW2aX;uJIFv\CCwdXPs[YFzKHS{YX7zcI9k[XSrb36gc4Yh|rJvY3H0[Y5qdg>? MX[yOVA3OTR7OR?=
SiHa NEHNUpRHfW6ldHnvckBCe3OjeR?= MUixNEDPxE1? NX3r[YdtPDhiaB?= M1LGU3Jm\HWldHnvckBw\iCleYTvdIxie22rYzDkbZN1emmkdYTpc44h[W6mIH71Z4xm[XJidILhcpNtd2OjdHnvckBw\iEQsj3jZZRmdmmw NXXUT5NiOjVyNkG0PVk>

... Click to View More Cell Line Experimental Data

In vivo試験
臨床試験
特集

プロトコル (参考用のみ)

細胞アッセイ: [1]

細胞株 WTK1 lymphoblasts
濃度 1.0 μM
反応時間 8 hours
実験の流れ 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.

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

SpeciesMouseRatRabbitGuinea pigHamsterDogMonkeyBaboon
Weight (kg)0.020.151.80.40.0810312
Body Surface Area (m2)0.0070.0250.150.050.020.50.240.6
Km factor361285201220
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.

Rat dose (mg/kg) = mouse dose (22.4 mg/kg) ×  mouse Km(3)  = 11.2 mg/kg
rat Km(6)
1

参考

化学情報

Download XAV-939 SDF
分子量 312.31
化学式

C14H11F3N2OS

CAS No. 284028-89-3
保管 2年-20℃
6月-80℃in solvent
別名 NVP-XAV939
溶解度 (25°C) * In vitro DMSO 12 mg/mL (38.42 mM)
<1 mg/mL (<1 mM)
エタノール <1 mg/mL (<1 mM)
In vivo 30% PEG400+0.5% Tween80+5% propylene glycol 30 mg/mL
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
化学名 2-(4-(trifluoromethyl)phenyl)-7,8-dihydro-5H-thiopyrano[4,3-d]pyrimidin-4-ol

カスタマーフィードバック (5)


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Rating
Source Nat Commun, 2014, 5, 5455. XAV-939 purchased from Selleck
Method Immunostaining
Cell Lines P19 cells
Concentrations 4 uM
Incubation Time 72 h
Results P19 cells transfected with expression vectors for the control or ​Cdo-shRNA with Top-flash and β-galactosidase were treated with either ​dimethylsuphoxide (​DMSO) or ​XAV939 (4 uM) in differentiation medium for 24 h. ​P19/control or P19/​Cdo shRNA cells were treated with ​DMSO or ​XAV939 in the differentiation medium for 72 h followed by immunostaining. XAV939-treated control cells displayed a modest increase in ​β-tubulin III-positive cells, compared with the control-treated cells. Furthermore, ​Cdo-depleted P19 cells treated with ​DMSO exhibited a significant reduction in ​β-tubulin III-positive cells, while ​XAV939 treatment restored neuronal differentiation of these cells nearly to the control level.

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Rating
Source Dis Model Mech, 2014, 7(10), 1193-203. XAV-939 purchased from Selleck
Method Immunostaining
Cell Lines TH+ cells
Concentrations
Incubation Time 72 h
Results XAV-nano increased total cell number, the percentage of TH+ cells was reduced. This is illustrated in Figure.

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Rating
Source Dr. Marco Quarta of Stanford University. XAV-939 purchased from Selleck
Method
Cell Lines
Concentrations 1-100 μM
Incubation Time
Results

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Rating
Source XAV-939 purchased from Selleck
Method Sectional Immunohistochemistry
Cell Lines E14.5 male UGSs
Concentrations 10 μM
Incubation Time 4 d
Results Total bud numbers were compared among vehicle9 (control), TCDD9 (1 nM), DKK1 + DKK29 (500 ng/ml each), and XAV-939-(10 μM) treated UGSs by staining the UGE for e-cadherin and counting prostatic buds. All treatments decreased the total number of prostatic buds compared to control UGSs (p<0.05, Fig. 1, bottom). A confocal image that is representative of the UGS for each treatment is also shown (Fig. 1, top).

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Rating
Source XAV-939 purchased from Selleck
Method Sectional Immunohistochemistry
Cell Lines E14.5 male UGSs
Concentrations 10 μM
Incubation Time 4 d
Results Cell elongation index measured from spindle-like morphology was used to determine the effect of individual inhibitors. Prevention of MSP-induced spindle-like morphology was not observed in M-RON cells treated with wortmannin, SB203580, SP600125, Cay10512, and S31-201, suggesting that signaling from these pathways was not involved in MSP-induced EMT. A moderate effect, based on changes in elongation index, was seen when rapamycin, vismodegib, and XAV-939 were applied, suggesting that signaling from Hedgehog, Wnt /b-catenin, and FRAP/mTOR pathways played a role in MSP-induced EMT.

文献中の引用 (21)

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
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