TW-37

SKU: orb1300906

Description

TW-37 is a small molecule, nonpeptide inhibitor targeting the anti-apoptotic proteins Bcl-2, Bcl-xL, and Mcl-1 with Kis of 0.29, 1.11, and 0.26 μM, respectively. It is widely used in cancer research to study apoptosis mechanisms and has demonstrated pro-apoptotic activity in various in vitro cellular assays and in vivo xenograft models.

Research Area

Cell Biology

Key Properties

• CAS Number: 877877-35-5
• MW: 573.7
• Purity: ≥95% (May vary between batches)
• Formula: C₃₃H₃₅NO₆S
• SMILES: CC(C)c1ccccc1Cc1cc(C(=O)Nc2ccc(cc2)S(=O)(=O)c2ccccc2C(C)(C)C)c(O)c(O)c1O
• Target: Bcl-2 Family
• Solubility: 10% DMSO+40% PEG300+5% Tween 80+45% Saline:2 mg/mL (3.49 mM);DMSO:57.4 mg/mL (100.05 mM)

Bioactivity

• Target IC50:
  Bcl-2:0.29 μM(Ki)|BCL-XL:1.11 μM(Ki)|MCL1:0.26 μM(Ki)
• In Vivo:
  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. 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. 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.
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• In Vitro:
  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. 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 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.
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• Cell Research:
  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(Only for Reference)
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Storage & Handling

• Storage: -20°C
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

Bcl-2, Bcl-2 Family, Bcl-xL, Mcl-1, Inhibitor, inhibit, TW 37, TW37, TW-37

Compound Identifiers

PubChem CID

11455910