TW-37

TW-37は、組み換え型Bcl-2(Bcl-xLとMcl-1)への新しい非ペプチド阻害剤で、Ki がそれぞれ 0.29 μM、1.11 μM、0.26 μMです。

目録号S1121
5 5 7レビュー 9製品表彰状
価格 在庫  
USD 183 In stock
USD 201 In stock
USD 856 In stock

TW-37 化学構造
分子量: 573.7

品質と確認

カスタマーレビュー(7)

Quality Control & MSDS

製品情報

  • Compare Bcl-2 Inhibitors
    Bcl-2阻害剤を比較
  • 研究分野

製品の説明

生物活性

情報 TW-37は、組み換え型Bcl-2(Bcl-xLとMcl-1)への新しい非ペプチド阻害剤で、Ki がそれぞれ 0.29 μM、1.11 μM、0.26 μMです。
目標 Bcl-2 Bcl-xL Mcl-1
IC50 0.29 μM (Ki) 1.11 μM (Ki) 0.26 μM (Ki) [1]
In vitro試験 TW-37 targets the BH3-binding groove in Bcl-2 where proapoptotic Bcl-2 proteins bind, and shows higher affinity and selectivity for Bcl-2 and Mcl-1 over Bcl-xL with Ki values of 0.29 μM, 0.26 μM and 1.11 μM, respectively. [1] In vitro, TW-37 shows significant anti-proliferative and pro-apoptotic effect in a de novo chemo-resistant WSU-DLCL2 lymphoma cell line and primary cells obtained from a lymphoma patient without effects on normal peripheral blood lymphocytes. [1] TW-37 exhibits the inhibitory effect on both cell growth and cell death in endothelial cell with IC50 of approximately 1.8 μM without effect on the fibroblasts exposed to the same concentration range as the endothelial cells. In addition, TW37 also shows the anti-proliferation effects in MCF-7, LNCaP, and SLK tumor cell lines with the same or lower concentration range than those required to inhibit endothelial cell growth. [2]
In vivo試験 TW-37 shows a maximum tolerated dose (MTD) of 40 mg/kg for three i.v. injections in severe combined immunodeficient (SCID) mice when given alone, and enhances tumor inhibitory effect of cyclophosphamide-doxorubicin-vincristine-prednisone (CHOP) regimen. [1] TW-37, administrated by i.v. produces the antiangiogenic effect by decreasing the density of functional human microvessels in the severe combined immunodeficient mouse model of human angiogenesis. [2] The combination of TW-37 and MEK inhibitors synergistically block melanoma cell growth in mice by a significant reduction in tumor volume and tumor mass. [3]
臨床試験 TW-37 is currently in Phase I/II clinical trials in patients with Chronic Lymphocytic Leukemia.
特集

推薦された実験操作 (公開の文献だけ)

キナーゼアッセイ: [1]

Fluorescence polarization-based binding assay for recombinant Bcl-2, Bcl-XL, and Mcl-1 protein For this assay, the 21-residue BH3 peptide QEDIIRNIARHLAQVGDSMDR derived from Bid labeled with 6-carboxyfluorescein succinimidyl ester (FAM-Bid) and recombinant proteins derived from human Bcl-2,Bcl-X L,and Mcl-1 are employed. It is determined that FAM-Bid has a Ki of 11 nM to Bcl-2 protein,25 nM to Bcl-XL protein,and 5.7 nM to Mcl-1 protein. The competitive binding assay for Bcl-XL is same as that for Bcl-2 with the following exceptions: 30 nM Bcl-XL protein and 2.5 nM FAM-Bid peptide in the following assay buffer [50 mM Tris-Bis (pH 7.4) and 0.01% bovine gamma-globulin].

細胞アッセイ: [2]

細胞系 HDMECs
濃度 0 - 100 μM
処理時間 96 hours
方法 The sulforhodamine B (SRB) cytotoxicity assay is used as described. Briefly, optimal cell density for cytotoxicity assay is determined by growth curve analysis. HDMECs are seeded in a 96-well plate and allowed to adhere overnight. Drug or control is diluted in EGM2-MV and layered onto cells, which are allowed to incubate for times as indicated in the figures. Alternatively, HDMECs are coincubated with TW37 and 0 to 100 ng/mL recombinant human VEGF (rhVEGF)165 or 0 to 100 ng/mL recombinant human CXCL8. Cells are fixed on the plates by addition of cold trichloroacetic acid (10% final concentration) and incubation for 1 hour at 4 °C. Cellular protein is stained by addition of 0.4% SRB in 1% acetic acid and incubation at room temperature for 30 minutes. Unbound SRB is removed by washing with 1% acetic acid and the plates are air dried. Bound SRB is resolubilized in 10 mM unbuffered Tris-base and absorbance is determined on a microplate reader at 560 nm. Test results are normalized against initial plating density and drug-free controls. Data are obtained from triplicate wells per condition and are representative of at least three independent experiments

動物実験: [3]

動物モデル Athymic NCr-nu/nu mice bearing SK-Mel-147 melanoma xenografts
製剤 TW-37 is resuspended in 1:1 Tween 80/ethanol (diluted 10-fold in 0.9% saline before use).
投薬量 ~40 mg/kg
管理 Administered via i.v. or i.p.
Solubility 30% propylene glycol, 5% Tween 80, 65% D5W 30 mg/mL
* 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.

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

SpeciesBaboonDogMonkeyRabbitGuinea pigRatHamsterMouse
Weight (kg)121031.80.40.150.080.02
Body Surface Area (m2)0.60.50.240.150.050.0250.020.007
Km factor202012128653
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 TW-37 SDF
分子量 573.7
化学式

C33H35NO6S

CAS No. 877877-35-5
保管 2年-20℃
6月-80℃in DMSO
別名
溶解度 (25°C) * In vitro DMSO 115 mg/mL (200.45 mM)
<1 mg/mL (<1 mM)
エタノール 4 mg/mL (6.97 mM)
In vivo 30% propylene glycol, 5% Tween 80, 65% D5W 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 5-(2-isopropylbenzyl)-N-(4-(2-tert-butylphenylsulfonyl)phenyl)-2,3,4-trihydroxybenzamide

研究分野

カスタマーレビュー (7)


Click to enlarge
Rating
Source Cell Death Differ, 2013, 20, 1475-84. TW-37 purchased from Selleck
Method electron microscopy
Cell Lines H23 cells
Concentrations 10 uM
Incubation Time 0-24 h
Results Ultrastructural examination of H23 cells exposed to TW-37 revealed early indications of apoptosis, characterised by chromatin condensation (8 h), and by 16–24 h extensive blebbing and secondary necrosis was observed. Pretreatment with a broad-spectrum caspase inhibitor, Z-VAD.fmk, completely blocked the induction of apoptosis.

Click to enlarge
Rating
Source Cell Death Differ, 2013, 20, 1475-84. TW-37 purchased from Selleck
Method western blot
Cell Lines H23 cells
Concentrations 10 uM
Incubation Time 0-24 h
Results TW-37 resulted in the activation of caspase-9 and the cleavage of poly (ADP-ribose) polymerase (PARP)

Click to enlarge
Rating
Source Cell Death Differ, 2013, 20, 1475-84. TW-37 purchased from Selleck
Method western blot
Cell Lines BAK-R Jurkats cells,BAK-def Jurkats cells
Concentrations 10 uM
Incubation Time 0-24 h
Results PARP cleavage, caspase-9 activation and PS externalisation were signicantly inhibited in BAK-deficient Jurkat cells

Click to enlarge
Rating
Source Cell Death Differ, 2013, 20, 1475-84. TW-37 purchased from Selleck
Method electron microscopy
Cell Lines BAK-R Jurkats cells,BAK-def Jurkats cells
Concentrations 10 uM
Incubation Time 0-24 h
Results The ultrastructural changes were significantly inhibited in BAK-deficient Jurkat cells

Click to enlarge
Rating
Source Cell Death Differ, 2012, 19, 1896-907. TW-37 purchased from Selleck
Method BAP31 staining
Cell Lines HeLa cells
Concentrations 20 μM
Incubation Time 4 h
Results Pan-BCL-2 family inhibitor TW37 induce ER membrane reorganisation more potently than BCL-2 and BCL-XL-specific inhibitors.

Click to enlarge
Rating
Source Dr. Christine Hawkins of La Trobe University. TW-37 purchased from Selleck
Method Cell Survival Assays
Cell Lines MEF cells
Concentrations 0-3 μM
Incubation Time 24 h
Results XL147 inhibited the survival of cell colonies and reduced propidium iodide uptake in a dose-dependent manner.

Click to enlarge
Rating
Source Dr. Zhang of Tianjin Medical University. TW-37 purchased from Selleck
Method Hoechst 33342 staining
Cell Lines MDB-MA-231 cells
Concentrations 100 nM
Incubation Time
Results

製品表彰状 (9)

技術サポート&よくある質問(FAQ)

顧客がするかもしれない質問に対する答えは、指示を取り扱っている阻害剤で見つかります。話題は、貯蔵液(阻害剤と特別な注意を細胞ベースの分析法と動物のために必要とする問題を保存することは実験します)を準備する方法を含みます。

電話番号: +1-832-582-8158 Ext:3月曜日〜金曜日 9:00 AM–5:00 PM (米国中部標準時)

他の問い合わせをするならば、メッセージを残してください。

* 必須

Related Bcl-2 阻害剤

  • Sabutoclax

    Sabutoclax is a pan-Bcl-2 inhibitor, including Bcl-xL, Bcl-2, Mcl-1 and Bfl-1 with IC50 of 0.31 μM, 0.32 μM, 0.20 μM and 0.62 μM, respectively.

  • UMI-77

    UMI-77 is a selective Mcl-1 inhibitor with Ki of 490 nM, showing selectivity over other members of Bcl-2 family.

  • GSK2606414

    GSK2606414 is an orally available, potent, and selective PERK inhibitor with IC50 of 0.4 nM, displaying at least 100-fold selectivity over the other EIF2AKs assayed.

  • GSK2656157

    GSK2656157 is an ATP-competitive and highly selective inhibitor of PERK with IC50 of 0.9 nM, 500-fold greater against a panel of 300 kinases.

  • ABT-737

    ABT-737は、Bcl-xL、Bcl-2とBcl-wのBH3模倣の阻害剤で、EC50 がそれぞれ78.7 nM、30.3 nM 、197.8 nMになる。

    Features:ABT-737是第一代抗凋亡BCL-2家族蛋白小分子抑制剂。

  • Obatoclax Mesylate (GX15-070)

    Obatoclax Mesylate (GX15-070)は Bcl-2 を抑制して、 Kiが0.22 μMになる.

    Features:Obatoclax是有应用前景的小分子Bcl-2拮抗剂,抑制Bcl-2蛋白家族所有相关的膜结构,包括 Mcl-1。

  • ABT-263 (Navitoclax)

    ABT-263(Navitoclax)は、 Bcl-xLBcl-2Bcl-w の強力な阻害剤で、Kiがそれぞれ ≤ 0.5 nM、≤1 nM 、≤ 1 nMです。

  • HA14-1

    HA14-1 is an inhibitor of Bcl-2 (IC50 of ≈9 µM).

  • AT101

    AT-101は、反アポトーシスのBcl-2 の強力な阻害剤であることを知られて、模倣のBH3家族です。

最近見られたアイテム

Tags: TW-37を買う | TW-37供給者 | TW-37を購入する | TW-37費用 | TW-37生産者 | オーダーTW-37 | TW-37代理店
お問い合わせ