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, respectively.

Price Stock Quantity  
In DMSO USD 146 In stock
USD 160 In stock
USD 680 In stock
Bulk Inquiry

Massive Discount Available

Free Overnight Delivery on all orders over $ 500.

TW-37 Chemical Structure

TW-37 Chemical Structure
Molecular Weight: 573.7

Validation & Quality Control

Customer Reviews(7)

Quality Control & MSDS

Related Compound Libraries

TW-37 is available in the following compound libraries:

Bcl-2 Inhibitors with Unique Features

  • Selective Bcl-2 Inhibitor

    ABT-199 (GDC-0199) Bcl-2-selective, Ki<0.01 nM.

  • Most Potent Bcl-2 Inhibitor

    ABT-263 (Navitoclax) Bcl-xL, Ki≤ 0.5 nM; Bcl-2, Ki≤ 1 nM; Bcl-w, Ki≤ 1 nM.

  • Inhibitor in Clinical Trial

    Obatoclax Mesylate (GX15-070) Phase II for leukemia, lymphoma, myelofibrosis, and mastocytosis.

  • Newest Bcl-2 Family Activator

    BAM7 Direct and selective activator of proapoptotic Bax with EC50 of 3.3 μM.

Product Information

  • Compare Bcl-2 Inhibitors
    Compare Bcl-2 Products
  • Research Area
  • Inhibition Profile

Product Description

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, respectively.
Targets Mcl-1 [1] Bcl-2 [1] Bcl-xL [1]
IC50 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]
Features

Protocol(Only for 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
Formulation TW-37 is resuspended in 1:1 Tween 80/ethanol (diluted 10-fold in 0.9% saline before use).
Dosages ~40 mg/kg
Administration 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

References

[1] Mohammad RM, et al. Clin Cancer Res, 2007, 13(7), 2226-2235.

[2] Zeitlin BD, et al. Cancer Res, 2006, 66(17), 8698-8706.

view more

Chemical Information

Download TW-37 SDF
Molecular Weight (MW) 573.7
Formula

C33H35NO6S

CAS No. 877877-35-5
Storage 3 years -20℃Powder
6 months-80℃in DMSO
Synonyms
Solubility (25°C) * In vitro DMSO 115 mg/mL (200 mM)
Water <1 mg/mL (<1 mM)
Ethanol 4 mg/mL (6 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.
Chemical Name 5-(2-isopropylbenzyl)-N-(4-(2-tert-butylphenylsulfonyl)phenyl)-2,3,4-trihydroxybenzamide

Research Area

Customer Reviews (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

Product Citations (9)

Tech Support & FAQs

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.

Tel: +1-832-582-8158 Ext:3

If you have any other enquiries, please leave a message.

* Indicates a Required Field

Related Bcl-2 Products

  • Nutlin-3a

    Nutlin-3a, the active enantiomer of Nutlin-3, inhibits the p53/MDM2 interaction with IC50 of 90 nM.

    Features:Highly selective MDM2 inhibitor with a much lower effect on MDMX. Most effective on tumors with wild type p53.

  • 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.

  • 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.

  • ABT-737

    ABT-737 is a BH3 mimetic inhibitor of Bcl-xL, Bcl-2 and Bcl-w with EC50 of 78.7 nM, 30.3 nM and 197.8 nM, respectively; no inhibition observed against Mcl-1, Bcl-B or Bfl-1. Phase 2.

  • Obatoclax Mesylate (GX15-070)

    Obatoclax (GX15-070) is an antagonist of Bcl-2 with Ki of 0.22 μM, can assist in overcoming MCL-1 mediated resistance to apoptosis. Phase 3.

    Features:Potential 1st-in-class small molecule antagonist of Bcl-2 designed to inhibit all relevant Bcl-2 family members, including Mcl-1.

  • ABT-263 (Navitoclax)

    ABT-263 (Navitoclax) is a potent inhibitor of Bcl-xL, Bcl-2 and Bcl-w with Ki of ≤ 0.5 nM, ≤1 nM and ≤1 nM, but binds more weakly to Mcl-1 and A1. Phase 2.

  • HA14-1

    HA14-1 is a non-peptidic ligand of a Bcl-2 surface pocket with IC50 of ~9 μM.

  • AT101

    AT101, the R-(-) enantiomer of Gossypol acetic acid, binds with Bcl-2, Bcl-xL and Mcl-1 with Ki of 0.32 μM, 0.48 μM and 0.18 μM; does not inhibit BIR3 domain and BID. Phase 2.

  • ABT-199 (GDC-0199)

    ABT-199 (GDC-0199) is a Bcl-2-selective inhibitor with Ki of <0.01 nM, >4800-fold more selective versus Bcl-xL and Bcl-w, and no activity to Mcl-1. Phase 3.

    Features:Re-engineered version of ABT-263 (Navitoclax).

  • BAM7

    BAM 7 is a direct and selective activator of proapoptotic Bax with EC50 of 3.3 μM.

    Features:Does not interact with the BH3-binding pocket of antiapoptotic proteins or proapoptotic BAK and induces cell death in a BAX-dependent fashion.

Recently Viewed Items

Tags: buy TW-37 | TW-37 supplier | purchase TW-37 | TW-37 cost | TW-37 manufacturer | order TW-37 | TW-37 distributor
Contact Us