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|Synonyms||TW 37;TW37; N-(4-((2-(tert-butyl)phenyl)sulfonyl)phenyl)-2,3,4-trihydroxy-5-(2-isopropylbenzyl)benzamide|
TW-37 is a novel nonpeptide inhibitor to recombinant Bcl-2, Bcl-xL and Mcl-1 with Ki of 0.29 μM, 1.11 μM and 0.26 μM, respectively. IC50 Value: 0.29 μM (Ki for Bcl-2) Target: Bcl-2 Family 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.
TW-37 is a potent small-molecule inhibitor of BCL-2 (Ki = 290 nmol/L), which attenuates BCL-2 activation and inhibits multiple BCL-2 family members including BCL-XL (Ki = 1,110 nmol/L) and MCL-1 (Ki = 260 nmol/L). It binds to the BCL-2 homology domain 3 (BH3) groove of BCL-2 preventing the heterodimerization of proapoptotic proteins (such as Bid, Bim, and Bad) with BCL-2 and subsequently allowing them to induce apoptosis. Recent studies indicate TW-37 is able to inhibit the growth of a broad range of cancer cells (such as breast, prostate, lymphoma, and pancreatic cancer), since it induces S-phase cell cycle arrest with regulation of several important cell cycle related genes, including p27, p57, E2F-1, cdc25A, CDK4, cyclin A, cyclin D1 and cyclin E.
Zhiwei Wang, Asfar Sohail Azmi, Aamir Ahmad, Sanjeev Banerjee, Shaomeng Wang, Fazlul H. Sarkar, and Ramzi M. Mohammad. TW-37, a small-molecule inhibitor of BCL-2, inhibits cell growth and induces apoptosis in pancreatic cancer: involvement of Notch-1 signaling pathway. Cancer Res 2009;69:2757-2765
Naoki Ashimori, Benjamin D. Zeitlin, Zhaocheng Zhang, Kristy Warner, IIan M. Turkienicz, Aaron C. Spalding, Theodoros N. Teknos, Shaomeng Wang, and Jacques E. Nor. TW-37, a small-molecule inhibitor of BCL-2, mediates S-phase cell cycle arrest and suppresses head and neck tumor angiogenesis. Mol Cancer Ther 2009;8:893-903......by Apexbio Technology LLC
|TW-37, a small-molecule inhibitor of Bcl-2, inhibits cell growth and induces apoptosis in pancreatic cancer mediated through a novel pathway involving inactivation of Notch-1 and Jagged-1. ......by BOC Sciences|
|TW-37 is a potent Bcl-2 inhibitor with Ki values of 260, 290 and 1110 nM for Mcl-1, Bcl-2 and Bcl-xL, respectively. ......by MedChemexpress Co., Ltd.|
|TW-37 is a small-molecule inhibitor of Bcl-2 family proteins, inhibited cell growth and induced apoptosis in pancreatic cancer. TW-37 induces cell growth inhibition and S-phase cell cycle arrest, with regulation of several important cell cycle-related genes like p27, p57, E2F-1, cdc25A, CDK4, cyclin A, cyclin D1, and cyclin E. The cell growth inhibition was accompanied by increased apoptosis with concomitant attenuation of Notch-1, Jagged-1, and its downstream genes such as Hes-1 in vitro and in vivo. Shelf life: >2 years if stored properly Drug formulation: ......by MedKoo Biosciences, Inc.|
|TW-37 is a novel nonpeptide inhibitor to recombinant Bcl-2, Bcl-xL and Mcl-1 with Ki of 0.29 μM, 1.11 μM and 0.26 μM in cell-free assays, respectively. ......by Selleck Chemicals LLC|
|TW-37 is a novel nonpeptide inhibitor to recombinant Bcl-2, Bcl-xL and Mcl-1 with Ki of 0.29 μM, 1.11 μM and 0.26 μM, respectively. ......by Target Molecule Corp.|
|Bcl-2 inhibitor (Ki values are 0.29 μM and 1.11 μM for Bcl-2 and Bcl-XL respectively). Inhibits the angiogenic potential of endothelial cells in vitro. Induces S-phase arrest and apoptosis in pancreatic cancer cell lines; also inhibits the activation of Notch-1 and Jagged-1 in vitro and in vivo. ......by Tocris Bioscience Inc.|
|Cell lines||BxPC-3 and Colo-357 cells|
|Conditions||750 nM, 72 hours for cell growth inhibition 500 nM, 48 hours for apoptosis induction (measured by Annexin V)|
|Method||The cell viability was assessed by the clonogenic assay. TW-37 resulted in a significant inhibition of colony formation of BxPC-3 and Colo-357 cells when compared with control. Besides that, TW-37 induced apoptosis in a dose- and time-dependent manner. In the Annexin V assay, the percentage of apoptotic cells increased from 5% to 6% in the control to 12% to 14% in both BxPC-3 and Colo-357 cell lines.|
|Source||Apexbio Technology LLC|
|Conditions||0 - 100 μM; 96 hours|
|Method||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|
|Source||Selleck Chemicals LLC|
|Animal Models||Female ICR-SCID mice bearing Colo-357 xenografts|
|Dosage Form||Intravenous injection, 20 mg/kg/d|
|Applications||TW-37 treatment significantly inhibited pancreatic tumor growth in vivo. Western blot analysis showed that the expression level of Notch-1 was significantly lower in tumors from the TW-37–treated mice than those from vehicle-treated control mice. In addition, the expression of Jagged-1 and Notch-1 downstream target gene, Hes-1, was also down-regulated in TW-37–treated tumors.|
|Source||Apexbio Technology LLC|
|Animal Models||Athymic NCr-nu/nu mice bearing SK-Mel-147 melanoma xenografts|
|Formulation||TW-37 is resuspended in 1:1 Tween 80/ethanol (diluted 10-fold in 0.9% saline before use).|
|Administration||Administered via i.v. or i.p.|
|Source||Selleck Chemicals LLC|
|Appearance:White to off-white Solid||EBNumber:EB000029011|
|Store at -20°C||by Apexbio Technology LLC|
|Store at -20°C||by Tocris Bioscience Inc.|
|Soluble in DMSO > 10 mM||by Apexbio Technology LLC|
|DMSO ≥112mg/mL Water <1.2mg/mL Ethanol ≥3.7mg/mL||by MedChemexpress Co., Ltd.|
|(25°C) * In vitro DMSO 115 mg/mL (200.45 mM); Ethanol4 mg/mL (6.97 mM); Water<1 mg/mL (<1 mM); In vivo 30% Propylene glycol, 5% Tween 80, 65% D5W30 mg/mL||by Selleck Chemicals LLC|
|Soluble to 100 mM in DMSO||by Tocris Bioscience Inc.|
|Company||Price and Availability||Country/Region|
|Apexbio Technology LLC||USA|
|Biochem Tek(Shanghai) Co., ltd.||China|
|MedChemexpress Co., Ltd.||10mg/USD160();50mg/USD650()||USA|
|MedKoo Biosciences, Inc.||USA|
|Selleck Chemicals LLC||10mM/1mLIn DMSO/USD146(In stock);10mg/USD160(In stock);50mg/USD680(In stock);200mg/USD1480(In stock)||USA|
|Shanghai Haoyuan Chemexpress Co., Ltd.||10mg/USD160();50mg/USD650()||China|
|Target Molecule Corp.||2mg/USD51();5mg/USD88();10mg/USD148();25mg/USD268();50mg/USD408()||USA|
|Tocris Bioscience Inc.||USA|
|Gossypol (acetic acid)||12542-36-8||C32H34O10||578.6064|
|Bax inhibitor peptide V5||579492-81-2||C27H50N6O6S||586.79|
. Zeitlin BD, Spalding AC, Campos MS, Ashimori N, Dong Z, Wang S, Lawrence TS, N?r JE.Metronomic small molecule inhibitor of Bcl-2 (TW-37) is antiangiogenic and potentiates the antitumor effect of ionizing radiation.Int J Radiat Oncol Biol Phys. 2010 Nov 1;78(3):879-87. Epub 2010 Aug 1.
. Al-Katib AM, Sun Y, Goustin AS, Azmi AS, Chen B, Aboukameel A, Mohammad RM.SMI of Bcl-2 TW-37 is active across a spectrum of B-cell tumors irrespective of their proliferative and differentiation status.J Hematol Oncol. 2009 Feb 16;2:8.
. Wang Z, Song W, Aboukameel A, Mohammad M, Wang G, Banerjee S, Kong D, Wang S, Sarkar FH, Mohammad RM.TW-37, a small-molecule inhibitor of Bcl-2, inhibits cell growth and invasion in pancreatic cancer.Int J Cancer. 2008 Aug 15;123(4):958-66.
| Wang Z, Azmi A S, Ahmad A, et al. TW-37, a small-molecule inhibitor of Bcl-2, inhibits cell growth and induces apoptosis in pancreatic cancer: involvement of Notch-1 signaling pathway. Cancer research, 2009, 69(7): 2757-2765. ......by Apexbio Technology LLC|
Wang et al (2006) Structure-based design of potent small-molecule inhibitors of anti-apoptotic Bcl-2 proteins. J.Med.Chem. 49 6139. PMID: 17034116.
Zeitlin et al (2006) Antiangiogenic effect of TW37, a small-molecule inhibitor of Bcl-2. Cancer Res. 66 8698. PMID: 16951185.
Ashimori et al (2009) TW-37, a small molecule inhibitor of Bcl-2, mediates S phase cell cycle arrest and suppresses head and neck tumor angiogenesis. Mol.Cancer.Ther. 8 893. PMID: 19372562.