ABT-737
ABT-737 (CAS 852808-04-9) is a small molecule inhibitor targeting the BCL-2 protein family, exhibiting high binding affinity toward the anti-apoptotic proteins BCL-2, BCL-X_L, and BCL-w. ABT-737 disrupts BCL-2/BAX protein interactions, leading to apoptosis primarily via the BAK-mediated intrinsic pathway, independent of BIM. In preclinical studies, ABT-737 demonstrated single-agent antitumor activity in lymphoma, multiple myeloma, and small-cell lung cancer models. Additionally, research indicates activity against acute myeloid leukemia (AML) cells, progenitor cells, and leukemia stem cells while sparing normal hematopoietic populations, highlighting its potential for therapeutic research in hematologic malignancies.
Reference
Marina Konopleva, Rooha Contractor, Twee Tsao, Ismael Samudio, Peter P. Ruvolo, Shinichi Kitada, Xingming Deng, Dayong Zhai, Yue-Xi Shi, Thomas Sneed, Monique Verhaegen, Maria Soengas, Vivian R. Ruvolo, Teresa McQueen, Wendy D. Schober, Julie C. Watt, Tilahun Jiffar, Xiaoyang Ling, Frank C. Marini, David Harris, Martin Dietrich, Zeev Estrov, James McCubrey, W. Stratford May, John C. Reed, and Michael Andreeff. Mechanisms of apoptosis sensitivity and resistance to the BH3 mimetic ABT-737 in acute myeloid leukemia. Cancer Cell 2006: 10; 375-388
Suzanne Trudel, A. Keith Stewart, Zhihua Li, Yanjun Shu, Sheng-Ben Liang, Young Trieu, Donna Reece, Josh Paterson, Dingyan Wang, and Xiao-Yan Wen. The Bcl-2 family protein inhibitor,ABT-737, has substantial antimyeloma activity and shows synergistic effect with dexamethasone and melphalan. Clin Cancer Res 2007; 13 (2) 621-629
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| Physical Appearance | A solid |
| Storage | Store at -20°C |
| M.Wt | 813.43 |
| Cas No. | 852808-04-9 |
| Formula | C42H45ClN6O5S2 |
| Synonyms | ABT 737, ABT737 |
| Solubility | ≥40.67 mg/mL in DMSO; insoluble in EtOH; insoluble in H2O |
| Chemical Name | 4-[4-[[2-(4-chlorophenyl)phenyl]methyl]piperazin-1-yl]-N-[4-[[(2R)-4-(dimethylamino)-1-phenylsulfanylbutan-2-yl]amino]-3-nitrophenyl]sulfonylbenzamide |
| SDF | Download SDF |
| Canonical SMILES | CN(C)CCC(CSC1=CC=CC=C1)NC2=C(C=C(C=C2)S(=O)(=O)NC(=O)C3=CC=C(C=C3)N4CCN(CC4)CC5=CC=CC=C5C6=CC=C(C=C6)Cl)[N+](=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: | |
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Cell lines |
Small-cell lung cancer (SCLC) cell (NCI-H889, NCI-H1963, NCI-H1417, NCI-H146, NCI-187, DMS79, NCI-1048, NCI-H82, NCI-H196, H69AR, and DMS114) lines. |
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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 |
48 h; 10 μM |
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Applications |
The ability of ABT-737 to inhibit cell proliferation with single-agent activity was evaluated against a panel of 11 kinds of SCLC cell lines. Ac-DEVD-AMC, a substrate for activated caspase 3, was used to treatment of H146 cells for 24 h. A dose-dependent increase in apoptosis coincided with a dose-dependent decrease in cell viability following ABT-737 treatment suggesting that ABT-737 inhibits cell proliferation through the induction of apoptosis. |
| Animal experiment: | |
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Animal models |
Lymphoma-prone Eμ- myc transgenic mice |
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Dosage form |
75 mg/kg body weight; the tail injection. |
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Applications |
All B-lymphoid subsets in the ABT-737-treatment (75 mg/kg) cohort were significantly decreased, compared with the vehicle-treated animals, in both the bone marrow and the spleen. Eμ- myc animals treated with ABT-737 contained significantly (**P |
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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] Tahir S K, Yang X, Anderson M G, et al. Influence of Bcl-2 family members on the cellular response of small-cell lung cancer cell lines to ABT-737[J]. Cancer research, 2007, 67(3): 1176-1183. [2] Kelly P N, Grabow S, Delbridge A R D, et al. Prophylactic treatment with the BH3 mimetic ABT-737 impedes Myc-driven lymphomagenesis in mice[J]. Cell Death & Differentiation, 2012, 20(1): 57-63. |
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| 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. | ||||||
| Targets | Bcl-xL | Bcl-2 | Bcl-w | |||
| IC50 | 78.7 nM (EC50) | 30.3 nM (EC50) | 197.8 nM (EC50) | |||
Quality Control & MSDS
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