2. Apoptosis
  3. Bcl-2 Family
  4. TW-37

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.

For research use only. We do not sell to patients.

TW-37 Chemical Structure

TW-37 Chemical Structure

CAS No. : 877877-35-5

Size Price Stock Quantity
Solid + Solvent (Highly Recommended)
10 mM * 1 mL in DMSO
ready for reconstitution
 USD 126 In-stock
Solution
10 mM * 1 mL in DMSO USD 126 In-stock
Solid
5 mg USD 100 In-stock
10 mg USD 160 In-stock
50 mg USD 450 In-stock
100 mg   Get quote  
200 mg   Get quote  

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Customer Review

Based on 2 publication(s) in Google Scholar

TW-37 Related Antibodies

Top Publications Citing Use of Products

View All Bcl-2 Family Isoform Specific Products:

View All Isoforms
Bcl-2 Bcl-xL Bcl-W Mcl-1 Bfl-1 Bcl-B Bax Bak Bim

  • Biological Activity

  • Protocol

  • Purity & Documentation

  • References

  • Customer Review

Description

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.

IC50 & Target[1][2]

Mcl-1

260 nM (Ki)

Bcl-2

290 nM (Ki)

Bcl-xL

1110 nM (Ki)

In Vitro

TW-37 (TW37) is a novel nonpeptide small-molecule inhibitor designed using a structure-based design strategy. TW-37 targets the BH3-binding groove in Bcl-2 where proapoptotic Bcl-2 proteins, such as Bak, Bax, and Bid bind. In fluorescence polarization-based binding assays using recombinant Bcl-2 and Bcl-xL proteins, TW-37 binds to Bcl-2 and Bcl-xL with Ki values of 290 and 1110 nM, respectively. TW-37 has an IC50 of 1.8 μM for endothelial cells but shows no cytotoxic effects for fibroblasts at concentrations up to 50 μM. The mechanism of TW-37-induced endothelial cell death is apoptosis, in a process mediated by mitochondrial depolarization and activation of caspase-9 and caspase-3. The effect of TW-37 on endothelial cell apoptosis is not prevented by coexposure to the growth factor milieu secreted by tumor cells. Inhibition of the angiogenic potential of endothelial cells (i.e., migration and capillary sprouting assays) and expression of the angiogenic chemokines CXCL1 and CXCL8 are accomplished at subapoptotic TW-37 concentrations (0.005-0.05 μM)[1]. TW-37 is a potent Bcl-2 and Mcl-1 inhibitor. In fluorescence polarization-based binding assays using recombinant Bcl-2, Bcl-xL, and Mcl-1 proteins, TW-37 binds to Bcl-2, Bcl-xL, and Mcl-1 with Ki values of 290, 1,110 and 260 nM, respectively[2].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

TW-37 Related Antibodies
In Vivo

A murine model of humanized vasculature is used to investigate the biological effect of TW-37 (TW37) on human microvascular endothelial cell in vivo. Using this model, a significant decrease is observed in total blood vessel number (P<0.05) comparing both 3 and 30 mg/kg TW-37 against vehicle control. In addition to reduction in total number of blood vessels, an unusual number of occluded vessels are occurring in the treated groups. The levels of vessel occlusion are assessed by counting completely blocked vessels and determining their number as a percentage of total vessel number. TW-37 concentration mediates a significant increase in the number of occluded vessels when compared with control[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Molecular Weight

573.70

Formula

C33H35NO6S
CAS No.
Appearance

Solid

Color

White to off-white

SMILES

O=C(C1=CC(CC2=CC=CC=C2C(C)C)=C(C(O)=C1O)O)NC3=CC=C(C=C3)S(=O)(C4=CC=CC=C4C(C)(C)C)=O
Shipping

Room temperature in continental US; may vary elsewhere.
Storage
Powder -20°C 3 years
4°C 2 years
In solvent -80°C 6 months
-20°C 1 month
Solvent & Solubility
In Vitro: 

DMSO : ≥ 42 mg/mL (73.21 mM; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

*"≥" means soluble, but saturation unknown.

Preparing
Stock Solutions
Concentration Solvent Mass 1 mg 5 mg 10 mg
1 mM 1.7431 mL 8.7154 mL 17.4307 mL
5 mM 0.3486 mL 1.7431 mL 3.4861 mL
View the Complete Stock Solution Preparation Table

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

  • Molarity Calculator

  • Dilution Calculator

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

Mass
=
Concentration
×
Volume
×
Molecular Weight *

Concentration (start) × Volume (start) = Concentration (final) × Volume (final)

This equation is commonly abbreviated as: C1V1 = C2V2

Concentration (start)

C1

×
Volume (start)

V1

=
Concentration (final)

C2

×
Volume (final)

V2

In Vivo:

Select the appropriate dissolution method based on your experimental animal and administration route.

For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for in vivo experiments, it is recommended to prepare freshly and use it on the same day.
The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

  • Protocol 1

    Add each solvent one by one:  10% DMSO    40% PEG300    5% Tween-80    45% Saline

    Solubility: ≥ 2.5 mg/mL (4.36 mM); Clear solution

    This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).

    Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.

    Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
  • Protocol 2

    Add each solvent one by one:  10% DMSO    90% (20% SBE-β-CD in Saline)

    Solubility: 2.08 mg/mL (3.63 mM); Suspended solution; Need ultrasonic

    This protocol yields a suspended solution of 2.08 mg/mL. Suspended solution can be used for oral and intraperitoneal injection.

    Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (20.8 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.

    Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
In Vivo Dissolution Calculator
Please enter the basic information of animal experiments:

Dosage

mg/kg

Animal weight
(per animal)

g

Dosing volume
(per animal)

μL

Number of animals

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
%
DMSO +
% 
+
%
Tween-80 +
%
Saline
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Calculation results:
Working solution concentration: mg/mL
Method for preparing stock solution: mg drug dissolved in μL  DMSO (Stock solution concentration: mg/mL).
The concentration of the stock solution you require exceeds the measured solubility. The following solution is for reference only. If necessary, please contact MedChemExpress (MCE).
Method for preparing in vivo working solution for animal experiments: Take μL DMSO stock solution, add μL . μL , mix evenly, next add μL Tween 80, mix evenly, then add μL Saline.
 If the continuous dosing period exceeds half a month, please choose this protocol carefully.
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
Purity & Documentation

Purity: 99.27%

COA (251 KB) LCMS (111 KB)

Handling Instructions (2659 KB)
References
Cell Assay
[1]

The sulforhodamine B (SRB) cytotoxicity assay is used. Briefly, optimal cell density for cytotoxicity assay, 2×104 to 3×104 cells per well, is determined by growth curve analysis. HDMECs are seeded at 2.5×104 per well 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 TW-37 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[1].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Administration
[1]

Mice[1]
Porous poly L-lactic acid scaffolds (6×6×1 mm) with an average pore diameter of 180 μm are fabricated. Just before implantation, scaffolds are seeded with 1×106 HDMECs in a 1:1 Matrigel/EGM2-MV mix. Male severe combined immunodeficient (SCID) mice (CB.17.SCID) are anesthetized with ketamine and xylazine, and two scaffolds are implanted s.c. in the dorsal region of each mouse. At 10 days after transplantation, six mice per treatment are treated with 3 mg/kg or 30 mg/kg TW-37 (in vehicle: PBS/Tween 80/ethanol) or vehicle alone i.v. for 5 consecutive days. At the end of the treatment period, mice are euthanized, and the scaffolds are retrieved, fixed overnight in 10% buffered formaldehyde at 4°C, and mounted on glass slides. Immunohistochemistry is done for Factor VIII and microvessels are counted in 6 fields per scaffold and 12 scaffolds per treatment at ×200 magnification. Alternatively, sections are stained with H&E and occluded blood vessels are counted.

MCE has not independently confirmed the accuracy of these methods. They are for reference only.
References

Complete Stock Solution Preparation Table

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

Optional Solvent Concentration Solvent Mass 1 mg 5 mg 10 mg 25 mg
DMSO 1 mM 1.7431 mL 8.7154 mL 17.4307 mL 43.5768 mL
5 mM 0.3486 mL 1.7431 mL 3.4861 mL 8.7154 mL
10 mM 0.1743 mL 0.8715 mL 1.7431 mL 4.3577 mL
15 mM 0.1162 mL 0.5810 mL 1.1620 mL 2.9051 mL
20 mM 0.0872 mL 0.4358 mL 0.8715 mL 2.1788 mL
25 mM 0.0697 mL 0.3486 mL 0.6972 mL 1.7431 mL
30 mM 0.0581 mL 0.2905 mL 0.5810 mL 1.4526 mL
40 mM 0.0436 mL 0.2179 mL 0.4358 mL 1.0894 mL
50 mM 0.0349 mL 0.1743 mL 0.3486 mL 0.8715 mL
60 mM 0.0291 mL 0.1453 mL 0.2905 mL 0.7263 mL
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TW-37 Related Classifications

Help & FAQs
  • Do most proteins show cross-species activity?

    Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

Keywords:

TW-37877877-35-5TW37TW 37Bcl-2 FamilyInhibitorinhibitorinhibit

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