Home Apoptosis Bcl-2 inhibitor TW-37 For research use only.

TW-37

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.

TW-37 Chemical Structure

TW-37 Chemical Structure

CAS No. 877877-35-5

Purity & Quality Control

TW-37 Related Products

Signaling Pathway

Bcl-2 Signaling Pathways

Bcl-2 Signaling Pathway

Cell Data

Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
human JAR cell Growth inhibition assay Inhibition of human JAR cell growth in a cell viability assay, IC50=2.6 nM SANGER
human Ca9-22 cell Growth inhibition assay Inhibition of human Ca9-22 cell growth in a cell viability assay, IC50=3.82 nM SANGER
human CHL-1 cell Growth inhibition assay Inhibition of human CHL-1 cell growth in a cell viability assay, IC50=11.9 nM SANGER
human A549 cell Growth inhibition assay Inhibition of human A549 cell growth in a cell viability assay, IC50=14.09 nM SANGER
human RKO cell Growth inhibition assay Inhibition of human RKO cell growth in a cell viability assay, IC50=15.17 nM SANGER
human GCIY cell Growth inhibition assay Inhibition of human GCIY cell growth in a cell viability assay, IC50=20.83 nM SANGER
human BHT-101 cell Growth inhibition assay Inhibition of human BHT-101 cell growth in a cell viability assay, IC50=21.83 nM SANGER
human Hs-578-T cell Growth inhibition assay Inhibition of human Hs-578-T cell growth in a cell viability assay, IC50=23.59 nM SANGER
human SK-UT-1 cell Growth inhibition assay Inhibition of human SK-UT-1 cell growth in a cell viability assay, IC50=28.68 nM SANGER
human NB7 cell Growth inhibition assay Inhibition of human NB7 cell growth in a cell viability assay, IC50=29.28 nM SANGER
human YKG-1 cell Growth inhibition assay Inhibition of human YKG-1 cell growth in a cell viability assay, IC50=29.76 nM SANGER
human HuH-7 cell Growth inhibition assay Inhibition of human HuH-7 cell growth in a cell viability assay, IC50=32.82 nM SANGER
human SAS cell Growth inhibition assay Inhibition of human SAS cell growth in a cell viability assay, IC50=33.18 nM SANGER
human UACC-62 cell Growth inhibition assay Inhibition of human UACC-62 cell growth in a cell viability assay, IC50=34.35 nM SANGER
human AGS cell Growth inhibition assay Inhibition of human AGS cell growth in a cell viability assay, IC50=37.53 nM SANGER
human SK-MEL-30 cell Growth inhibition assay Inhibition of human SK-MEL-30 cell growth in a cell viability assay, IC50=37.97 nM SANGER
human A427 cell Growth inhibition assay Inhibition of human A427 cell growth in a cell viability assay, IC50=44.69 nM SANGER
human DU-145 cell Growth inhibition assay Inhibition of human DU-145 cell growth in a cell viability assay, IC50=52.13 nM SANGER
human HCT-116 cell Growth inhibition assay Inhibition of human HCT-116 cell growth in a cell viability assay, IC50=52.66 nM SANGER
human A673 cell Growth inhibition assay Inhibition of human A673 cell growth in a cell viability assay, IC50=53.85 nM SANGER
human SF126 cell Growth inhibition assay Inhibition of human SF126 cell growth in a cell viability assay, IC50=57.07 nM SANGER
human SW872 cell Growth inhibition assay Inhibition of human SW872 cell growth in a cell viability assay, IC50=58.9 nM SANGER
human NCI-H1581 cell Growth inhibition assay Inhibition of human NCI-H1581 cell growth in a cell viability assay, IC50=67.64 nM SANGER
human SK-MEL-5 cell Growth inhibition assay Inhibition of human SK-MEL-5 cell growth in a cell viability assay, IC50=69.25 nM SANGER
human CP50-MEL-B cell Growth inhibition assay Inhibition of human CP50-MEL-B cell growth in a cell viability assay, IC50=69.59 nM SANGER
human YH-13 cell Growth inhibition assay Inhibition of human YH-13 cell growth in a cell viability assay, IC50=70.59 nM SANGER
human LXF-289 cell Growth inhibition assay Inhibition of human LXF-289 cell growth in a cell viability assay, IC50=72.85 nM SANGER
human MC-IXC cell Growth inhibition assay Inhibition of human MC-IXC cell growth in a cell viability assay, IC50=75.33 nM SANGER
human NB14 cell Growth inhibition assay Inhibition of human NB14 cell growth in a cell viability assay, IC50=76.45 nM SANGER
human HEC-1 cell Growth inhibition assay Inhibition of human HEC-1 cell growth in a cell viability assay, IC50=81.37 nM SANGER
human U-87-MG cell Growth inhibition assay Inhibition of human U-87-MG cell growth in a cell viability assay, IC50=82.24 nM SANGER
human HOS cell Growth inhibition assay Inhibition of human HOS cell growth in a cell viability assay, IC50=84.71 nM SANGER
human HUTU-80 cell Growth inhibition assay Inhibition of human HUTU-80 cell growth in a cell viability assay, IC50=87.01 nM SANGER
human A375 cell Growth inhibition assay Inhibition of human A375 cell growth in a cell viability assay, IC50=88.83 nM SANGER
human A204 cell Growth inhibition assay Inhibition of human A204 cell growth in a cell viability assay, IC50=97.84 nM SANGER
human GB-1 cell Growth inhibition assay Inhibition of human GB-1 cell growth in a cell viability assay, IC50=98.69 nM SANGER
human MDA-MB-231 cell Growth inhibition assay Inhibition of human MDA-MB-231 cell growth in a cell viability assay, IC50=0.10807 μM SANGER
human SW982 cell Growth inhibition assay Inhibition of human SW982 cell growth in a cell viability assay, IC50=0.1107 μM SANGER
human SW756 cell Growth inhibition assay Inhibition of human SW756 cell growth in a cell viability assay, IC50=0.11236 μM SANGER
human MG-63 cell Growth inhibition assay Inhibition of human MG-63 cell growth in a cell viability assay, IC50=0.11248 μM SANGER
human Daoy cell Growth inhibition assay Inhibition of human Daoy cell growth in a cell viability assay, IC50=0.14073 μM SANGER
human MDA-MB-453 cell Growth inhibition assay Inhibition of human MDA-MB-453 cell growth in a cell viability assay, IC50=0.15188 μM SANGER
human HT-144 cell Growth inhibition assay Inhibition of human HT-144 cell growth in a cell viability assay, IC50=0.15201 μM SANGER
human LoVo cell Growth inhibition assay Inhibition of human LoVo cell growth in a cell viability assay, IC50=0.16093 μM SANGER
human NY cell Growth inhibition assay Inhibition of human NY cell growth in a cell viability assay, IC50=0.17762 μM SANGER
human SW1783 cell Growth inhibition assay Inhibition of human SW1783 cell growth in a cell viability assay, IC50=0.21301 μM SANGER
human A2780 cell Growth inhibition assay Inhibition of human A2780 cell growth in a cell viability assay, IC50=0.21846 μM SANGER
human MDA-MB-361 cell Growth inhibition assay Inhibition of human MDA-MB-361 cell growth in a cell viability assay, IC50=0.2264 μM SANGER
human RPMI-2650 cell Growth inhibition assay Inhibition of human RPMI-2650 cell growth in a cell viability assay, IC50=0.23831 μM SANGER
Click to View More Cell Line Experimental Data

Biological Activity

Description 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.
Targets
Mcl-1 [1]
(Cell-free assay)		 Bcl-2 [1]
(Cell-free assay)		 Bcl-xL [1]
(Cell-free assay)
0.26 μM(Ki) 0.29 μM(Ki) 1.11 μM(Ki)
In vitro
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. [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]
Kinase Assay 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 the 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].
Cell Research Cell lines HDMECs
Concentrations 0 - 100 μM
Incubation Time 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
In Vivo
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 the 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]
Animal Research Animal Models Athymic NCr-nu/nu mice bearing SK-Mel-147 melanoma xenografts
Dosages ~40 mg/kg
Administration Administered via i.v. or i.p.

Chemical Information & Solubility

Molecular Weight 573.7 Formula

C33H35NO6S
CAS No. 877877-35-5 SDF Download TW-37 SDF
Smiles CC(C)C1=CC=CC=C1CC2=CC(=C(C(=C2O)O)O)C(=O)NC3=CC=C(C=C3)S(=O)(=O)C4=CC=CC=C4C(C)(C)C
Storage (From the date of receipt)

In vitro
Batch:

DMSO : 115 mg/mL ( (200.45 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Ethanol : 4 mg/mL

Water : Insoluble


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In vivo
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Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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