AT406 (SM-406)

製品コードS2754

AT406 (SM-406)化学構造

分子量(MW):561.71

AT406 (SM-406) は一種の有効で、Smac模倣のIAP(E3ユビキチンリガーゼを通じて、役立つアポトーシス阻害剤)拮抗剤で、XIAP-BIR3、cIAP1-BIR3及びcIAP2-BIR3と結合する時のKi値が66.4 nM、1.9 nMと5.1 nMにそれぞれ分かれることですが、IAPに作用する親和力はSmac AVPIペプチドに作用する親和力より50倍-100倍が高くなります。臨床1期。

サイズ 価格(税別)  
JPY 27722.00
JPY 82502.00

カスタマーフィードバック(5)

  • G, cells treated with the SM406 (1 μmol/L) for 48 hours were subjected to Western blotting.

    Cancer Res, 2015, 75(8):1736-48. . AT406 (SM-406) purchased from Selleck.

    HepG2 cells were treated with AT406 (10 μM) or plus OSI-027 (“OSI”, 100 nM), cells were further cultured for indicated periods of time, expression of listed proteins was tested by Western blotting assay (A). HepG2 cells transfected with scramble non-sense control siRNA (“NS-siRNA”) or Mcl-1 siRNA (“-1/-2”, 200 nM each, 24 hours) were stimulated with AT406 (10 μM) for indicated periods of time, Mcl-1 expression (B, upper panel); Cell viability (B, lower panel) and cell apoptosis (C) were tested. *indicated statistically significant differences as compared to “Ctrl” group. ##indicated statistically significant differences as compared to “NS-siRNA” group.

    Oncotarget, 2017, 8(6):9466-9475. AT406 (SM-406) purchased from Selleck.

  • (C) The U2OS cells were treated with TRAIL for 5 h, and with or without pre-treatment of A(AT406) for 1 h, and transient transfection with c-FLIP-siRNA for 24 h as indicated in the graph.

    Int J Oncol, 2016, 49(1):153-63. . AT406 (SM-406) purchased from Selleck.

    AT406 is cytotoxic to human pancreatic cancer cells. Panc-1 cells (A-C), Mia-PaCa-2 cells (D), primary human pancreatic cancer cells (“Primary Pan Can”, D) or epithelial HPDE6c7 cells (D) were either left untreated (“Ctrl”, same for all figures) or stimulated with applied concentrations of AT406 (10-1000 nM) for indicated periods of time, cell survival was tested by CellTiter-Glo luminescent assay (A and D) and the clonogenic assay (B); Cell proliferation was tested by BrdU incorporation assay (C). All values were expressed as mean ± SD. For each assay, n = 5. Experiments in this figure were repeated three times, and similar results were obtained. *p < 0.05 vs. group of “Ctrl”.

    Biochem Biophys Res Commun, 2016, 478(1):293-9. . AT406 (SM-406) purchased from Selleck.

  • Liposomal C6 ceramide sensitizes AT406-induced anti-pancreatic cancer activity in vivo. Panc-1 tumor bearing SCID mice (n = 10 of each group) were administrated at Day-1, 2, 3, 8, 15 and 22 with vehicle control (“Saline”), AT406 (5 mg/kg body weight, gavage) and/or plus liposomal C6 ceramide (“Lipo C6”, 25 mg/kg body weight, i.v.), tumor volumes (A), tumor daily growth (in mm3 per day, B) and mice body weights (in grams, C) were recorded; Expression of listed proteins in the xenografted tumor tissues (Day-3 after initial AT406 plus “Lipo C6” co-administration, two tumors per set) was tested by Western blot assay (D) and IHC staining assay (E, for Bcl-2). “Combine” stands for AT406 plus liposomal C6 ceramide co-administration. *p < 0.05 vs. group of “Saline”. #p < 0.05 vs. group of AT406 only. Bar = 100 μm (E).

    Biochem Biophys Res Commun, 2016, 479(2):166-172.. AT406 (SM-406) purchased from Selleck.

製品安全説明書

IAP阻害剤の選択性比較

生物活性

製品説明 AT406 (SM-406) は一種の有効で、Smac模倣のIAP(E3ユビキチンリガーゼを通じて、役立つアポトーシス阻害剤)拮抗剤で、XIAP-BIR3、cIAP1-BIR3及びcIAP2-BIR3と結合する時のKi値が66.4 nM、1.9 nMと5.1 nMにそれぞれ分かれることですが、IAPに作用する親和力はSmac AVPIペプチドに作用する親和力より50倍-100倍が高くなります。臨床1期。
ターゲット
cIAP1-BIR3 [1]
(cell-free assay)
cIAP2-BIR3 [1]
(cell-free assay)
XIAP-BIR3 [1]
(cell-free assay)
1.9 nM(Ki) 5.1 nM(Ki) 66.4 nM(Ki)
体外試験

AT-406 is a Smac mimetic and appears to mimic closely the AVPI peptide in both hydrogen bonding and hydrophobic interactions with XIAP, with additional hydrophobic contacts with W323 of XIAP. AT-406 is more sensitive to these IAPs than Smac AVPI peptide with 50-100 fold binding affinities. AT-406 (at 1 μM) completely restores the activity of caspase-9, which is suppressed by 500 nM XIAP BIR3 in a cell-free system. In MDA-MB-231 cell, AT-406 induces rapid cellular cIAP1 degradation and also pulls down the cellular XIAP protein. AT-406 effectively inhibits lots of human cancer cell lines and shows IC50 of 144 and 142 nM in MDA-MB-231 cell and SK-OV-3 ovarian cell, with low toxicity against normal-like human breast epithelial MCF-12F cells and primary human normal prostate epithelial cells. AT-406 induces apoptosis in MDA-MB-231 cell by inducing activation of caspase-3 and cleavage of PARP. [1]

細胞データ
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
EVSA-T cells M3[3dWN6fG:2b4jpZ4l1gSCjc4PhfS=> NGHQ[lA4OiCq MX3DfZRwfG:6aXPpeJkh[WejaX7zeEBpfW2jbjDz[Y5{cXSrdnWgSXZUSS2WIHPlcIx{KGG|c3Xzd4VlKGG|IHnubIljcXSrb36gc4Yh[2WubDDndo94fGhiYX\0[ZIhPzJiaILzJIJ6KEGuYX3hdkBDdHWnIHHzd4F6NCCHQ{WwQVAvODB{MTFOwG0> MVeyOlIyQDJ4NB?=
MDA-MB-231 cells NWH0Omk2S3m2b4TvfIlkcXS7IHHzd4F6 MXy3NkBp MYXDfZRwfG:6aXPpeJkh[WejaX7zeEBpfW2jbjDz[Y5{cXSrdnWgUWRCNU2ELUKzNUBk\WyuczDhd5Nme3OnZDDhd{BqdmirYnn0bY9vKG:oIHPlcIwh\3Kxd4ToJIFnfGW{IEeyJIhzeyCkeTDBcIFu[XJiQnz1[UBie3OjeTygSWM2OD1yLkCxPUDPxE1? MVOyOlIyQDJ4NB?=
HEK293 cells NVnrRlQ{TnWwY4Tpc44h[XO|YYm= MXSyJIg> NU\Y[XpiSW62YXfvcol{fCCjY4Tpeol1gSCjdDDmeYxtNWynbnf0bEBHVEGJLYTh[4dm\CC[SVHQJEh2dmuwb4fuJI9zcWerbjmgeJJidnOoZXP0[YQhcW5iSFXLNlk{KGOnbHzzJIF{e2W|c3XkJIF{KGmwaHnibZRqd25ib3[gbY51\XKjY4Tpc44hf2m2aDDjZZNx[XOnIEmgZYZ1\XJiMjDodpMh[nliaX3teY5weHKnY3nwbZRifGmxbjDhd5NigSxiRVO1NF0xNjB|NDFOwG0> MWOyOlIyQDJ4NB?=
human SKOV3 cells NGP2bJVIem:5dHigbY5pcWKrdHnvckBie3OjeR?= NF35[oQ1KGSjeYO= Ml;5S5Jwf3SqIHnubIljcXSrb36gc4YhcHWvYX6gV2tQXjNiY3XscJMh[W[2ZYKgOEBl[Xm|IHL5JHdUXDhiYYPzZZktKEmFNUC9NE4yPDJizszN NIG2cG8zOTR2M{KzNi=>
MDA-MB-231 cells NUnGTYd3T3Kxd4ToJIlvcGmkaYTpc44h[XO|YYm= MX:0JIRigXN? NHvQZopIem:5dHigbY5pcWKrdHnvckBw\iCqdX3hckBOTEFvTVKtNlMyKGOnbHzzJIFnfGW{IESg[IF6eyCkeTDXV3Q5KGG|c3H5MEBKSzVyPUCuNVQ1KM7:TR?= MUiyNVQ1OzJ|Mh?=
MDA-MB-231 cells NFr2eYZHfW6ldHnvckBie3OjeR?= M1jwNFEvPSEQvF2= NYrPUm5HOTJiaB?= MXTJcoR2[3Srb36gc4Yh[XCxcITvd4l{KGmwIHj1cYFvKE2GQT3NRk0zOzFiY3XscJMh[XO|ZYPz[YQh[XNiYXP0bZZifGmxbjDv[kBRSVKSIHPs[YF3[WenIHH0JFEvPSC3TTDh[pRmeiBzMjDodpMh[nliV3XzeIVzdiCkbH;0JIFv[Wy7c3nz M2i2SlIyPDR|MkOy

多くの細胞株試験データを見る場合、クリックしてください

体内試験 AT-406 has good pharmacokinetic (PK) properties and oral bioavailability in mice, rats, non-human primates, and dogs. In the MDA-MB-231 xenograft, AT-406 effectively induces cIAP1 degradation and processing of procaspase-8, cleavage of PARP in tumor tissues at 100 mg/kg with well toleration even at 200 mg/kg. AT-406 induces significant tumor growth inhibition with p of 0.0012 at 100 mg/kg. [1]

お薦めの試験操作(参考用のみ)

キナーゼ試験:

[1]

+ 展開

Fluorescence Polarization Based Assays for XIAP, cIAP1, and cIAP2 BIR3 Proteins:

FL-AT-406 (the fluorescently tagged AT-406) is employed to develop a set of new FP assays for determination of the binding affinities of Smac mimetics to XIAP, cIAP-1, and cIAP-2 BIR3 proteins. The Kd value of FL-AT-406 to each IAP protein is determined by titration experiments using a fixed concentration of FL-AT-406 and different concentrations of the protein up to full saturation. Fluorescence polarization values are measured using an Infinite M-1000 plate reader in Microfluor 2 96-well, black, round-bottom plates. To each well, FL-AT-406 (2, 1, and 1 nM for experiments with XIAP BIR3, cIAP-1 BIR3, and cIAP-2 BIR3, respectively) and different concentrations of the protein are added to a final volume of 125 μL in the assay buffer (100 mM potassium phosphate, pH 7.5, 100 μg/mL bovine γ-globulin, 0.02% sodium azide, with 4% DMSO). Plates are mixed and incubated at room temperature for 2-3 hours with gentle shaking. The polarization values in millipolarization units (mP) are measured at an excitation wavelength of 485 nm and an emission wavelength of 530 nm. Equilibrium dissociation constants (Kd) are then calculated by fitting the sigmoidal dose-dependent FP increases as a function of protein concentrations using Graphpad Prism 5.0 software. In competitive binding experiments for XIAP3 BIR3, AT-406 is incubated with 20 nM XIAP BIR3 protein and 2 nM FL-AT-406 in the assay buffer (100 mM potassium phosphate, pH 7.5; 100 μg/mL bovine γ-globulin; 0.02% sodium azide). In competitive binding experiments for cIAP1 BIR3 protein, 3 nM protein and 1 nM FL-AT-406 are used. In competitive binding experiments for cIAP2 BIR3, 5 nM protein and 1 nM FL-AT-406 are used. For each competitive binding experiment, polarization values are measured after 2-3 hours of incubation using an Infinite M-1000 plate reader. The IC50 value, the inhibitor concentration at which 50% of the bound tracer is displaced, is determined from the plot using nonlinear least-squares analysis. Curve fitting is performed using the PRISM software. A Ki value for AT-406 is calculated.
細胞試験:

[1]

+ 展開
  • 細胞株: MDA-MB-231 breast cancer and SK-OV-3 ovarian cancer cell lines
  • 濃度: ~ 1 μM
  • 反応時間: 4 days
  • 実験の流れ:

    Cells are seeded in 96-well flat bottom cell culture plates at a density of (3-4) × 103 cells/well with AT-406 and incubated for 4 days. The rate of cell growth inhibition after treatment with different concentrations of AT-406 is determined by assaying with (2-(2-methoxy-4-nitrophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium monosodium salt (WST-8). WST-8 is added to each well to a final concentration of 10%, and then the plates are incubated at 37 °C for 2−3 hours. The absorbance of the samples is measured at 450 nm using a TECAN ULTRA reader. Concentration of AT-406 that inhibited cell growth by 50% (IC50) is calculated by comparing absorbance in the untreated cells and the cells treated with AT-406.


    (参考用のみ)
動物試験:

[1]

+ 展開
  • 動物モデル: MDA-MB-231 xenograft tumors in severe combined immune deficiency (SCID) mice
  • 製剤: HCl salt form of AT-406 in water
  • 投薬量: 10 mg/kg (i.v.), 10 mg/kg (p.o.), 30 mg/kg (p.o.) and 100 mg/kg (p.o.)
  • 投与方法: Administered via intravenously (i.v.) or oral gavage (p.o.)
    (参考用のみ)

溶解度 (25°C)

体外 DMSO 100 mg/mL (178.02 mM)
Ethanol 100 mg/mL (178.02 mM)
Water Insoluble
体内 順序で溶剤を入れること:
30% propylene glycol, 5% Tween 80, 65% D5W
30 mg/mL

* 溶解度検測はSelleck技術部門によって行いますので、文献より提供された溶解度と差異がある可能性がありますが、生産工芸と不同ロット(lot)で起きる正常な現象ですから、ご安心ください。

化学情報

分子量 561.71
化学式

C32H43N5O4

CAS No. 1071992-99-8
保管
別名

便利ツール

モル濃度計算器

モル濃度計算器

解決のために必要とされるマス、ボリュームまたは濃度を計算してください。

マス (g) = 濃度 (mol/L) x ボリューム (L) x 分子量 (g/mol)

モル濃度計算器方程式

  • マス
    濃度
    ボリューム
    分子量

*貯蔵液を準備するとき、常に、オンであるとわかる製品のバッチに特有の分子量を使って、を通してラベルとMSDS/COA(製品ページで利用可能な)。

希釈計算器

希釈計算器

貯蔵液を準備することを要求される希釈剤を計算してください. セレック希釈計算器は、以下の方程式に基づきます:

開始濃度 x 開始体積 = 最終濃度 x 最終体積

希釈の計算式

この方程式は、一般に略語を使われます:C1V1 = C2V2 ( 輸入 輸出 )

  • C1
    V1
    C2
    V2

常に貯蔵液を準備するとき、小びんラベルとMSDS/COA(オンラインで利用できる)で見つかる製品のバッチに特有の分子量を使ってください。

連続希釈計算器方程式

  • 連続希釈剤

  • 計算結果

  • C1=C0/X C1: LOG(C1):
    C2=C1/X C2: LOG(C2):
    C3=C2/X C3: LOG(C3):
    C4=C3/X C4: LOG(C4):
    C5=C4/X C5: LOG(C5):
    C6=C5/X C6: LOG(C6):
    C7=C6/X C7: LOG(C7):
    C8=C7/X C8: LOG(C8):
分子量計算器

分子量计算器

そのモル質量と元素組成を計算するために、合成物の化学式を入力してください:

総分子量:g/mol

チップス: 化学式は大文字と小文字の区別ができます。C10H16N2O2 c10h16n2o2

モル濃度計算器

マス 濃度 ボリューム 分子量

技術サポート

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Handling Instructions

他の質問がある場合は、お気軽くお問合せください。

  • * 必須

Related Antibodies

IAP信号経路図

Tags: AT406 (SM-406)を買う | AT406 (SM-406) ic50 | AT406 (SM-406)供給者 | AT406 (SM-406)を購入する | AT406 (SM-406)費用 | AT406 (SM-406)生産者 | オーダーAT406 (SM-406) | AT406 (SM-406)化学構造 | AT406 (SM-406)分子量 | AT406 (SM-406)代理店
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細胞株 試験類型 濃度 培養時間 溶剤類型 活性叙述 PMID