ABT-737は一種のBH3模倣の阻害剤で、無細胞試験でBcl-xL、Bcl-2とBcl-wに作用する時のEC50値が78.7 nM、30.3 nMと197.8 nMにそれぞれ分かれることですが、Mcl-1、Bcl-BとBfl-1を抑制する作用がありません。臨床2期。
Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, 2015, 10.1016/j.mrfmmm.2015.04.005
Cardiomyocytes transduced with or without Ad-Mst1 were treated with ABT-737 (0, 0.1, 1, 10 uM) for 12 hours. Representative immunoblots with antibodies to p62/SQSTM1, LC3 and GAPDH are shown.
Nat Med 2013 19(11), 1478-88. ABT-737 purchased from Selleck.
BCL-XL mediates human neutrophil survival. PMNs were preincubated with the BH3 mimetic ABT-737 (1–10 μM), then cultured in normoxia (gray bars) with or without GM-CSF (500 U/ml) or hypoxia (white bars)or 20 hours, and apoptosis was assessed by morphology (n = 4).
J Clin Invest 2011 121, 1053-1063. ABT-737 purchased from Selleck.
Release of mitochondrial cytochrome c and loss of mitochondrial membrane potential after exposure to ABT-737 (100nM) for 2 hours were assessed by immunohistochemistry and staining with TMRE (red, top panels) and anti-CD41/FITC (green, top panels). Bar represents 5 um. Note that control cells display spreading on glass slides, whereas ABT-737-treated cells do not.
Blood 2011 17(26), 7145-54. ABT-737 purchased from Selleck.
Platelets were incubated in HBS with or without ABT-737 (100nM) for 2 hours before analysis by immunohistochemistry and confocal microscopy. Actin was stained using phalloidin/Alexa-488 (green), and tubulin was stained using anti-tubulin/phycoerythrin (red). Bar represents 5 uM.
Blood 2011 17(26), 7145-54. ABT-737 purchased from Selleck.
(B) The sensitivity (LD50) of CLL cells, assessed by annexin V staining after 48 h of treatment with ABT‐737, ABT‐263 or ABT‐199, was plotted against the pBcl‐2/Bcl‐2, Mcl‐1/Bcl‐2 and (pBcl‐2 + Mcl‐1)/Bcl‐2 ratios. Relative protein quantification was carried out with kodak carestream molecular imaging software and normalized to β‐actin. Spearman's correlation (r) and P values are shown. Data shown are representative of five independent experiments.
Br J Pharmacol, 2016, 173(3):471-83. ABT-737 purchased from Selleck.
Bcl-XL/Bcl-2 inhibitor ABT-737 aggravates the proapoptotic effects of IL-1IFN-. INS-1E cells were transfected with single or smart Pool PUMA siRNAs and exposed to ABT-737 for 24 h. At this time point, cell death was measured by HO/PI, n 3. *, p 0.05; **, p 0.01.
J Biol Chem 2010 285, 19919-19920. ABT-737 purchased from Selleck.
Upper panel ABT-737 inhibits TFK-1 and EGI-1 cell growth.Cells were exposed to ABT-737 at a concentration ranging from 1 to 50 lM. Following 72 h of incubation, growth inhibition was analyzed by crystal violet assay. Dose–effect plot of ABT-737 treatment is presented.
Cancer Chemoth Pharm 2011 67, 557-567. ABT-737 purchased from Selleck.
3 μM ABT737 inhibited growth and viability of TF-1 cells and potentiated proapoptotic effects of 1 μM BIO after 72 hours treatment. TF-1 cells treated with both drugs exhibited more apoptotic cells compared to those treated with each single drug. ABT737 abrogated the protection from BIO-induced apoptosis provided by MS5 coculture.
Exp Hematol 2010 38, 908-921. ABT-737 purchased from Selleck.
Apoptosis induced by BCL2-inhibitors in P-glycoprotein expressing cells. MDCKII wild type or MDR1 cells were exposed to different concentrations of ABT-737 (C) or ABT-263 (D) for 24 h before apoptosis was assessed by flow cytometry using externalization of phosphatidylserine.
Biochem Biophys Res Commun 2012 408, 344-9. ABT-737 purchased from Selleck.
GSIXII synergized with ABT-737 to trigger apoptosis in breast cancer cells . Breast cancer cell lines were incubate d for 48 hours with 10μM GSIXII or DMSO (Ct) in combination or not with ABT-737, 1 μM. Then apoptosis was evaluated with Apo2.7 or Annexin-V staining and flow-cytometry analysis. Represented data are the means of positive cells ± SEM, from three independent experiments.(A) Suboptimal concentrations of GSIXII (5 μM) and 1 μM ABT-737 were used alone or in combination in MFU assay in MCF7 and BT549 cell lines. Results were obtained from three independent experiments and compared with mock-treated condition. (B) The 20 μM SAHM1 was used alone or in combination in MFU assay in MCF7 and BT549 cell lines. Results were obtained from three independent experiments and compared with the mock-treated condition.
Biochem Biophys Res Commun 2013 408, 344-9. ABT-737 purchased from Selleck.
The combined use of ABT-737 and sorafenib changes the apoptotic effect. MC-3 cells were treated with the indicated compounds for 48 h. (A) Nuclear condensation and fragmentation were evaluated in DAPI-stained cells as described in the Materials and Methods (X400). (B) Live (green) and dead (red) cells were qualified using the Live/dead assay kit as described in the Materials and Methods (X200). (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)
Arch Oral Biol, 2017, 73:1-6. ABT-737 purchased from Selleck.
MEF wt and MEF Mcl-1 ko mice activating active caspase-3 using 1um ABT for 24h
Dr. Arnim Weber of Medizinische Mikrobiologie und Hygiene Universitatsklinikum Freiburg. ABT-737 purchased from Selleck.
|製品説明||ABT-737は一種のBH3模倣の阻害剤で、無細胞試験でBcl-xL、Bcl-2とBcl-wに作用する時のEC50値が78.7 nM、30.3 nMと197.8 nMにそれぞれ分かれることですが、Mcl-1、Bcl-BとBfl-1を抑制する作用がありません。臨床2期。|
|特性||First-generation inhibitor of anti-apoptotic Bcl-2 proteins.|
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.  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.  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.  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.  A recent study shows that ABT-737 significantly induces apoptosis in HTLV-1 infected T-cell lines as well as in fresh ATLL cells. 
|体内試験||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.  ABT-737 prolongs the survival of recipient mice transplanted with Bcl-2-transduced tumors.  ABT-737 shows great antitumor activity in an ATLL mouse model at a dose of 100 mg/kg. |
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.
-  Konopleva M, et al. Cancer Cell, 2006, 10(5), 375-388.
-  van Delft MF,et al. Cancer Cell, 2006, 10(5), 389-399.
-  Del Gaizo Moore V, et al. J Clin Invest, 2007, 117(1), 112-121.
-  Tahir SK, et al. Cancer Res, 2007, 67(3), 1176-1183.
-  Ishitsuka K, et al. Cancer Lett, 2012, 317(2), 218-225.
-  Konopleva M, et al. Cancer Res, 2008, 68(9), 3413-3420.
-  Wade M, et al. Cell Cycle, 2008, 7(13), 1973-1982.
-  Paoluzzi L, et al. Blood, 2008, 112(7), 2906-2916.
-  Li R, et al. Mol Pharmacol, 2009, 75(5), 1231-1239.
|体外||DMSO||100 mg/mL (122.93 mM)|
|Water||slightly soluble or insoluble|
|Ethanol||slightly soluble or insoluble|
30% Propylene glycol, 5% Tween 80, 65% D5W
マス (g) = 濃度 (mol/L) x ボリューム (L) x 分子量 (g/mol)
開始濃度 x 開始体積 = 最終濃度 x 最終体積
この方程式は、一般に略語を使われます：C1V1 = C2V2 ( 輸入 輸出 )
チップス: 化学式は大文字と小文字の区別ができます。C10H16N2O2 c10h16n2o2
What’s the recommended method about reconstitution of the compound for in vivo animal study?
For oral administration, we suggest the vehicle: 30% Propylene glycol, 5% Tween 80, 65% D5W, at up to 30mg/ml; For injection, ABT-737 can be dissolved in 2% DMSO/50% PEG 300/5% Tween 80/ddH2O at 2.5 mg/ml.