ABT-737

Catalog No.S1002 Batch:S100212

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Technical Data

Formula

C42H45ClN6O5S2
Molecular Weight 813.43 CAS No. 852808-04-9
Solubility (25°C)* In vitro DMSO 100 mg/mL (122.93 mM)
Water Insoluble
Ethanol Insoluble
In vivo (Add solvents to the product individually and in order)
Clear solution
2%DMSO 40%PEG300 5%Tween80 53%ddH2O
2.0mg/ml Taking the 1 mL working solution as an example, add 20 μL of 100 mg/ml clarified DMSO stock solution to 400 μL PEG300, mix evenly to clarify it; add 50 μL Tween80 to the above system, mix evenly to clarify it; then continue to add 530 μL ddH2O 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 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 in cell-free assays, respectively; no inhibition observed against Mcl-1, Bcl-B or Bfl-1. ABT-737 induces mitochondrial pathway apoptosis and mitophagy. Phase 2.
Targets
Bcl-2 [1]
(Cell-free assay)		 Bcl-xL [1]
(Cell-free assay)		 Bcl-w [1]
(Cell-free assay)		 Bcl-B [1]
(Cell-free assay)
30.3 nM(EC50) 78.7 nM(EC50) 197.8 nM(EC50) 1.82 μM(EC50)
In vitro ABT-737 shows low activity to Bcl-B and no effects to Mcl-1 and BFL-1. ABT-737 is sensitive to HL60, KG1 and NB4 cells with IC50 of 50 nM, 80 nM and 80 nM, respectively. ABT-737 induces apoptosis in HL60 cells, which due to decreased Bcl-2/Bax heterodimerization and has no effect on cell cycle distribution. ABT-737 also induces cytochrome c release from purified mitochondria and promotes conformational changes in Bax that are associated with apoptosis. [1] Resistant cells (Hela and MCF-7) can be sensitized to ABT-737 by approaches that down-regulate, destabilize, or inactivate Mcl-1. ABT-737 also causes Bax/BAK-dependent cytochrome c release only when Mcl-1 has been neutralized. [2] ABT-737 displaces Bim from Bcl2's BH3-binding pocket, allowing Bim to activate Bax, induce mitochondrial permeabilization, and rapidly commit the primary chronic lymphocytic leukemia (CLL) cells to death. [3] Knockdown of Mcl-1 with siRNA sensitizes two resistant SCLC cell lines H196 and DMS114 to ABT-737 by enhancing the induction of apoptosis. Likewise, up-regulation of Noxa sensitizes H196 cells to ABT-737. ABT-737 inhibits proliferation and induces apoptosis in many SCLC cell lines including NCI-H889, NCI-H1963, NCI-H1417, NCI-H146 and etc. Bcl-2 and Noxa may contribute mechanistically to the cellular response to ABT-737 in NCI-H146 cells. [4] A recent study shows that ABT-737 significantly induces apoptosis in HTLV-1 infected T-cell lines as well as in fresh ATLL cells. [5]
In vivo In aggressive leukemia model, ABT-737 suppresses the leukemia burden by 53% at the 30 mg/kg, with significantly extended survival of mice. ABT-737 does not induce significantly abnormalities in blood cell counts or serum chemistries. [1] ABT-737 prolongs the survival of recipient mice transplanted with Bcl-2-transduced tumors. [2] ABT-737 shows great antitumor activity in an ATLL mouse model at a dose of 100 mg/kg. [5]
Features First-generation inhibitor of anti-apoptotic Bcl-2 proteins.

Protocol (from reference)

Kinase Assay:

[1]
  • Fluorescence polarization assays

    Binding affinity of GST-Bcl-2 family proteins to the FITC-conjugated BH3 domain of Bim (FITC-Ahx-DMRPEIWIAQELRRIGDEFNAYYAR) is determined. Briefly, 100 nM of GST-Bcl-2 family fusion proteins are incubated with serial dilutions of ABT-737 in PBS for 2 min. Then, 20 nM of FITC-Bim BH3 peptide (FITC-Ahx-DMRPEIWIAQELRRIGDEFNAYYAR) is added. Fluorescence polarization is measured using an Analyst TM AD Assay Detection System after 10 min using the 96-well black plate. Then IC50 are determined.
Cell Assay:

[4]
  • Cell lines

    SCLC cell lines NCI-H889, NCI-H1963, NCI-H1417, NCI-H146, NCI-187, DMS79, NCI-1048, NCI-H82, NCI-H196, H69AR, and DMS114

  • Concentrations

    0.001-10 μM

  • Incubation Time

    48 hours

  • Method

    SCLC cells are treated for 48 hours in 96-well tissue culture plates in a total volume of 100 μL tissue culture medium supplemented with 10% human serum. Viable cells are determined using the MTS assay.
Animal Study:

[1]
  • Animal Models

    Scid mice injected with Luc-expressing FD/ΔRaf-1:ER cells

  • Dosages

    20 and 30 mg/kg

  • Administration

    For intraperitoneal (i.p.) every day

Customer Product Validation

Data from [Nat Med, 2013, 19(11), 1478-88]

Data from [Cell Death Dis, 2013, 4, e801]

Data from [Biochem Biophys Res Commun, 2013, 408, 344-9]

Data from [Biochem Biophys Res Commun, 2012, 408, 344-9]

Selleck's ABT-737 has been cited by 378 publications

Dual Inhibition of CDK4/6 and XPO1 Induces Senescence With Acquired Vulnerability to CRBN-Based PROTAC Drugs [ Gastroenterology, 2024, S0016-5085(24)00062-3] PubMed: 38262581
Mitophagy curtails cytosolic mtDNA-dependent activation of cGAS/STING inflammation during aging [ Nat Commun, 2024, 15(1):830] PubMed: 38280852
Detection of senescence using machine learning algorithms based on nuclear features [ Nat Commun, 2024, 15(1):1041] PubMed: 38310113
BH3 mimetics and azacitidine show synergistic effects on juvenile myelomonocytic leukemia [ Leukemia, 2024, 38(1):136-148] PubMed: 37945692
Inhibitor PF-04691502 works as a senolytic to regulate cellular senescence [ Exp Gerontol, 2024, 186:112359] PubMed: 38184267
Tau activation of microglial cGAS-IFN reduces MEF2C-mediated cognitive resilience [ Nat Neurosci, 2023, 26(5):737-750] PubMed: 37095396
Intracellular FGF1 protects cells from apoptosis through direct interaction with p53 [ Cell Mol Life Sci, 2023, 80(10):311] PubMed: 37783936
STING agonism turns human T cells into interferon-producing cells but impedes their functionality [ EMBO Rep, 2023, e55536.] PubMed: 36705069
HPV-induced host epigenetic reprogramming is lost upon progression to high-grade cervical intraepithelial neoplasia [ Int J Cancer, 2023, 152(11):2321-2330] PubMed: 36810770
SARS-CoV-2 E and 3a Proteins Are Inducers of Pannexin Currents [ Cells, 2023, 12(11)1474] PubMed: 37296595

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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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