TW-37

Catalog No.S1121 Batch:S112103

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Technical Data

Formula

C33H35NO6S
Molecular Weight 573.7 CAS No. 877877-35-5
Solubility (25°C)* In vitro DMSO 100 mg/mL (174.3 mM)
Water Insoluble
Ethanol Insoluble
In vivo (Add solvents to the product individually and in order)
Clear solution
30%propylene glycol 5%Tween80 65%D5W
30.0mg/ml Taking the 1 mL working solution as an example, add 300 μL of 100 mg/ml clarified propylene glycol stock solution to 50 μL of Tween 80, mix evenly to clarify it; then continue to add 650 μL of D5W to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results. 
* <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.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

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 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 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]

Protocol (from reference)

Kinase Assay:[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].
Cell Assay:[2]
  • 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
Animal Study:[3]
  • 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.

Customer Product Validation

Data from [Data independently produced by Cell Death Differ, 2013, 20, 1475-84]

Data from [Data independently produced by Cell Death Differ, 2013, 20, 1475-84]

Data from [Data independently produced by Cell Death Differ, 2013, 20, 1475-84]

Data from [Data independently produced by Cell Death Differ, 2013, 20, 1475-84]

Selleck's TW-37 has been cited by 50 publications

Gravitational and mechanical forces drive mitochondrial translation [ bioRxiv, 2024, 10.1101/2023.01.18.524628] PubMed: none
Obatoclax Rescues FUS-ALS Phenotypes in iPSC-Derived Neurons by Inducing Autophagy [ Cells, 2023, 12(18)2247] PubMed: 37759469
Obatoclax Rescues FUS-ALS Phenotypes in iPSC-Derived Neurons by Inducing Autophagy [ Cells, 2023, 10.3390/cells12182247] PubMed: 37759469
Mcl-1 inhibition overcomes BET inhibitor resistance induced by low FBW7 expression in breast cancer [ J Cell Mol Med, 2022, 10.1111/jcmm.17210] PubMed: 35132755
Prediction and identification of synergistic compound combinations against pancreatic cancer cells [ iScience, 2021, 24(9):103080] PubMed: 34585118
Development and implementation of the SUM breast cancer cell line functional genomics knowledge base [ NPJ Breast Cancer, 2020, 6:30] PubMed: 32715085
Comparison of putative BH3 mimetics AT-101, HA14-1, sabutoclax and TW-37 with ABT-737 in platelets. [ Platelets, 2020, 10.1080/09537104.2020.1724276] PubMed: 32079453
KIM-1/TIM-1 is a Receptor for SARS-CoV-2 in Lung and Kidney [ medRxiv, 2020, 2020.09.16.20190694] PubMed: 32995803
The small molecule Bcl-2/Mcl-1 inhibitor TW-37 shows single-agent cytotoxicity in neuroblastoma cell lines. [ BMC Cancer, 2019, 19(1):243] PubMed: 30885150
NRL and CRX Define Photoreceptor Identity and Reveal Subgroup-Specific Dependencies in Medulloblastoma. [ Cancer Cell, 2018, 33(3):435-449] PubMed: 29533784

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

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