ABT-737

製品コードS1002 バッチS100211

印刷

化学情報

Chemical Structure Synonyms N/A Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C42H45ClN6O5S2
分子量 813.43 CAS No. 852808-04-9
Solubility (25°C)* 体外 DMSO 100 mg/mL (122.93 mM)
Water Insoluble
Ethanol Insoluble
* <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.

溶剤液（一定の濃度）を調合する

生物活性

製品説明 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.
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]
特徴 First-generation inhibitor of anti-apoptotic Bcl-2 proteins.

プロトコル(参考用のみ)

キナーゼアッセイ 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.
細胞アッセイ 細胞株 SCLC cell lines NCI-H889, NCI-H1963, NCI-H1417, NCI-H146, NCI-187, DMS79, NCI-1048, NCI-H82, NCI-H196, H69AR, and DMS114
濃度 0.001-10 μM
反応時間 48 hours
実験の流れ

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.
動物実験 動物モデル Scid mice injected with Luc-expressing FD/ΔRaf-1:ER cells
投薬量 20 and 30 mg/kg
投与方法 For intraperitoneal (i.p.) every day

カスタマーフィードバック

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]

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

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

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

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