TW-37
TW-37 is a potent small-molecule inhibitor of BCL-2 (Ki = 290 nmol/L), which attenuates BCL-2 activation and inhibits multiple BCL-2 family members including BCL-XL (Ki = 1,110 nmol/L) and MCL-1 (Ki = 260 nmol/L). It binds to the BCL-2 homology domain 3 (BH3) groove of BCL-2 preventing the heterodimerization of proapoptotic proteins (such as Bid, Bim, and Bad) with BCL-2 and subsequently allowing them to induce apoptosis. Recent studies indicate TW-37 is able to inhibit the growth of a broad range of cancer cells (such as breast, prostate, lymphoma, and pancreatic cancer), since it induces S-phase cell cycle arrest with regulation of several important cell cycle related genes, including p27, p57, E2F-1, cdc25A, CDK4, cyclin A, cyclin D1 and cyclin E.
Reference
Zhiwei Wang, Asfar Sohail Azmi, Aamir Ahmad, Sanjeev Banerjee, Shaomeng Wang, Fazlul H. Sarkar, and Ramzi M. Mohammad. TW-37, a small-molecule inhibitor of BCL-2, inhibits cell growth and induces apoptosis in pancreatic cancer: involvement of Notch-1 signaling pathway. Cancer Res 2009;69:2757-2765
Naoki Ashimori, Benjamin D. Zeitlin, Zhaocheng Zhang, Kristy Warner, IIan M. Turkienicz, Aaron C. Spalding, Theodoros N. Teknos, Shaomeng Wang, and Jacques E. Nor. TW-37, a small-molecule inhibitor of BCL-2, mediates S-phase cell cycle arrest and suppresses head and neck tumor angiogenesis. Mol Cancer Ther 2009;8:893-903
- 1. In-Hyoung Yang, Seung-Hyun Hong, et al. "Cryptotanshinone chemosensitivity potentiation by TW-37 in human oral cancer cell lines by targeting STAT3–Mcl-1 signaling." Cancer Cell Int 2020 Aug 26;20:405. PMID:32863764
- 2. Chi-Hyun Ahn, Won Woo Lee, et al. "Antitumor effect of TW-37, a BH3 mimetic in human oral cancer." Laboratory Animal Research. 04 December 2019.
- 3. Villalobos-Ortiz M, Ryan J, et al. "BH3 profiling discriminates on-target small molecule BH3 mimetics from putative mimetics." Cell Death Differ. 2019 Jul 22. PMID:31332296
- 4. Yang IH, Ahn CH, et al. "Heme Oxygenase-1 is a Key Molecule Underlying Differential Response of TW-37-Induced Apoptosis in Human Mucoepidermoid Carcinoma Cells." Molecules. 2019 May 1;24(9). pii: E1700. PMID:31052354
- 5. Russo M, Milito A, et al. "CK2 and PI3K are direct molecular targets of quercetin in chronic lymphocytic leukaemia." Oncotarget. 2017 Jun 27;8(26):42571-42587. PMID:28489572
| Storage | Store at -20°C |
| M.Wt | 573.7 |
| Cas No. | 877877-35-5 |
| Formula | C33H35NO6S |
| Synonyms | TW37,TW 37 |
| Solubility | insoluble in H2O; ≥19.75 mg/mL in DMSO; ≥3.41 mg/mL in EtOH with gentle warming and ultrasonic |
| Chemical Name | N-[4-(2-tert-butylphenyl)sulfonylphenyl]-2,3,4-trihydroxy-5-[(2-propan-2-ylphenyl)methyl]benzamide |
| SDF | Download SDF |
| Canonical SMILES | CC(C)C1=CC=CC=C1CC2=C(C(=C(C(=C2)C(=O)NC3=CC=C(C=C3)S(=O)(=O)C4=CC=CC=C4C(C)(C)C)O)O)O |
| Shipping Condition | Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice. |
| General tips | We do not recommend long-term storage for the solution, please use it up soon. |
| Cell experiment: [1] | |
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Cell lines |
BxPC-3 and Colo-357 cells |
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Preparation method |
The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while.Stock solution can be stored below -20°C for several months. |
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Reaction Conditions |
750 nM, 72 hours for cell growth inhibition 500 nM, 48 hours for apoptosis induction (measured by Annexin V) |
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Applications |
The cell viability was assessed by the clonogenic assay. TW-37 resulted in a significant inhibition of colony formation of BxPC-3 and Colo-357 cells when compared with control. Besides that, TW-37 induced apoptosis in a dose- and time-dependent manner. In the Annexin V assay, the percentage of apoptotic cells increased from 5% to 6% in the control to 12% to 14% in both BxPC-3 and Colo-357 cell lines. |
| Animal experiment: [1] | |
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Animal models |
Female ICR-SCID mice bearing Colo-357 xenografts |
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Dosage form |
Intravenous injection, 20 mg/kg/d |
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Applications |
TW-37 treatment significantly inhibited pancreatic tumor growth in vivo. Western blot analysis showed that the expression level of Notch-1 was significantly lower in tumors from the TW-37–treated mice than those from vehicle-treated control mice. In addition, the expression of Jagged-1 and Notch-1 downstream target gene, Hes-1, was also down-regulated in TW-37–treated tumors. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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References: [1] Wang Z, Azmi A S, Ahmad A, et al. TW-37, a small-molecule inhibitor of Bcl-2, inhibits cell growth and induces apoptosis in pancreatic cancer: involvement of Notch-1 signaling pathway. Cancer research, 2009, 69(7): 2757-2765. |
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| 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 | Bcl-2 | Bcl-xL | Mcl-1 | |||
| IC50 | 0.29 μM (Ki) | 1.11 μM (Ki) | 0.26 μM (Ki) | |||
Quality Control & MSDS
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