ABT-737

製品コードS1002 バッチS100210

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
体内 （毎回新しく調製した物を用意してください）
Homogeneous suspension
CMC-NA
≥5mg/ml Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
* <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. This compound is sensitive to HL60, KG1 and NB4 cells with IC50 of 50 nM, 80 nM and 80 nM, respectively. It induces apoptosis in HL60 cells, which due to decreased Bcl-2/Bax heterodimerization and has no effect on cell cycle distribution. It 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 this chemical by approaches that down-regulate, destabilize, or inactivate Mcl-1. It also causes Bax/BAK-dependent cytochrome c release only when Mcl-1 has been neutralized. [2] This compound 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 it by enhancing the induction of apoptosis. Likewise, up-regulation of Noxa sensitizes H196 cells to this chemical. It 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 it in NCI-H146 cells. [4] A recent study shows that it 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. This compound does not induce significantly abnormalities in blood cell counts or serum chemistries. [1] It prolongs the survival of recipient mice transplanted with Bcl-2-transduced tumors. [2] This chemical 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 with ABT-737 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

参考

  • https://pubmed.ncbi.nlm.nih.gov/17097560/
  • https://pubmed.ncbi.nlm.nih.gov/17097561/
  • https://pubmed.ncbi.nlm.nih.gov/17200714/
  • https://pubmed.ncbi.nlm.nih.gov/17283153/
  • https://pubmed.ncbi.nlm.nih.gov/22138435/
  • https://pubmed.ncbi.nlm.nih.gov/18451169/
  • https://pubmed.ncbi.nlm.nih.gov/18604177/
  • https://pubmed.ncbi.nlm.nih.gov/18591385/
  • https://pubmed.ncbi.nlm.nih.gov/19246337/

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：

Anti-BCL2 therapy eliminates giant congenital melanocytic nevus by senolytic and immune induction [ Signal Transduct Target Ther, 2025, 10(1):161] PubMed: 40374605
Host hepatocyte senescence determines the success of hepatocyte transplantation in a mouse model of liver injury [ J Hepatol, 2025, S0168-8278(24)02830-7] PubMed: 39755157
Selective apoptosis of tumor-associated platelets boosts the anti-metastatic potency of PD-1 blockade therapy [ Cell Rep Med, 2025, S2666-3791(25)00057-6] PubMed: 40020674
Beclin 1 of megakaryocytic lineage cells is locally dispensable for platelet hemostasis but functions distally in bone homeostasis [ Bone Res, 2025, 13(1):32] PubMed: 40032858
Oncogenic and microenvironmental signals drive cell type specific apoptosis resistance in juvenile myelomonocytic leukemia [ Cell Death Dis, 2025, 16(1):165] PubMed: 40057493
Metabolic adaptations to acute glucose uptake inhibition converge upon mitochondrial respiration for leukemia cell survival [ Cell Commun Signal, 2025, 23(1):47] PubMed: 39863913
Senescent Microglia Mediate Neuroinflammation-Induced Cognitive Dysfunction by Selective Elimination of Excitatory Synapses in the Hippocampal CA1 [ Aging Cell, 2025, e70167] PubMed: 40624910
The anticancer effect of the HDAC inhibitor belinostat is enhanced by inhibitors of Bcl-xL or Mcl-1 in ovarian cancer [ Mol Oncol, 2025, 10.1002/1878-0261.70050] PubMed: 40483575
The anticancer effect of the HDAC inhibitor belinostat is enhanced by inhibitors of Bcl-xL or Mcl-1 in ovarian cancer [ Mol Oncol, 2025, 10.1002/1878-0261.70050] PubMed: 40483575
Acute suppression of mitochondrial ATP production prevents apoptosis and provides an essential signal for NLRP3 inflammasome activation [ Immunity, 2024, S1074-7613(24)00492-8] PubMed: 39571574

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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