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ABT-263 (Navitoclax) (Synonyms: Navitoclax,ABT-263,ABT263,ABT 263)

Catalog No.GC12405

ABT-263 (Navitoclax) is a inhibitor of Bcl-xL, Bcl-2 and Bcl-w, with Ki ≤0.5 nM, ≤1 nM and ≤1 nM respectively[1].

Products are for research use only. Not for human use. We do not sell to patients.

ABT-263 (Navitoclax) Chemical Structure

Cas No.: 923564-51-6

Size Price Stock Qty
10mM (in 1mL DMSO)
$74.00
In stock
5mg
$39.00
In stock
10mg
$53.00
In stock
50mg
$151.00
In stock
100mg
$246.00
In stock

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Sample solution is provided at 25 µL, 10mM.

Product has been cited by 2 publications

Product Documents

Quality Control & SDS

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Protocol

Kinase experiment [1]:

Preparation Method

Ki or IC50 values of ABT-263 (Navitoclax) on different subtypes of the Bcl-2 family were determined by competitive fluorescence polarization assay using the following peptide probe pairs or protein pairs :f-bad (1 nM) and Bcl-xL (6 nM), f-Bax (1 nM) and Bcl-2 (10 nM),f-Bax (1 nM) and Bcl-w (40 nM), f-Noxa (2 nM) and Mcl-1 (40 nM),and f-Bax (1 nM) and Bcl-2-A1 (15 nM) were used to determine the binding tightness of ABT-263 and Bcl-xL by time-resolved fluorescence resonance energy transfer method. Bcl-xL with His label was used for 1 nM and 200 nM f-Bak and 1 nMTb-labeled His antibodies were mixed and then treated at room temperature for 30 minutes.

Applications

ABT-263 (Navitoclax) is a inhibitor of Bcl-xL, Bcl-2 and Bcl-w, with Ki ¡ܰ.5 nM, ¡ܱ nM and ¡ܱ nM respectively.

Cell experiment [2]:

Cell lines

HeLa, U2OS, OVCAR-5, and A549 cell

Preparation Method

In four cancer cell lines, nvitokera (ABT-263) was treated with 1 ¦̭ol/L alone or in combination with other agents. Individual cells were monitored by phase-contrast and fluorescence time-lapse microscopy, and time from mitotic entry to morphologic death was measured and plotted as cumulative survival curves.

Reaction Conditions

1μM ;60 hours

Applications

Navitoclax accelerates apoptosis mainly by inhibiting Bcl-xL.

Animal experiment [3]:

Animal models

H345 transplanted tumor model(C.B.-17 scid-bg (scid-bg) or C.B.-17 scid (scid) mice)

Preparation Method

Mice were implanted with H345 cells maintained by in vivo propagation. Noculation volume was 0.2 mL consisting of 50% Matrigel. When tumors reached the appropriate tumor volume, mice were size matched (day 0) into treatment(ABT-263 (Navitoclax)) and control groups.

Dosage form

100 mg/kg/day ABT-263 (Navitoclax);p.o. ;once daily for 21 days

Applications

ABT-263 (Navitoclax) treated a mouse model inoculated with H345 cells, and significant antitumor efficacy was observed.

References:

[1]. Tse C, Shoemaker AR, et,al. ABT-263: a potent and orally bioavailable Bcl-2 family inhibitor. Cancer Res. 2008 May 1;68(9):3421-8. doi: 10.1158/0008-5472.CAN-07-5836. PMID: 18451170.

[2].Shi J, Zhou Y, Huang HC, Mitchison TJ. Navitoclax (ABT-263) accelerates apoptosis during drug-induced mitotic arrest by antagonizing Bcl-xL. Cancer Res. 2011 Jul 1;71(13):4518-26. doi: 10.1158/0008-5472.CAN-10-4336. Epub 2011 May 5. PMID: 21546570; PMCID: PMC3129452.

[3]. Shoemaker AR, Mitten MJ, et,al.Activity of the Bcl-2 family inhibitor ABT-263 in a panel of small cell lung cancer xenograft models. Clin Cancer Res. 2008 Jun 1;14(11):3268-77. doi: 10.1158/1078-0432.CCR-07-4622. PMID: 18519752.

Background

ABT-263 (Navitoclax) is a inhibitor of Bcl-xL, Bcl-2 and Bcl-w, with Ki ≤0.5 nM, ≤1 nM and ≤1 nM respectively[1].

ABT-263 (Navitoclax) is senolytic in some, but not all types of senescent cells: Navitoclax reduced viability of senescent human umbilical vein epithelial cells (HUVECs), IMR90 human lung fibroblasts, and murine embryonic fibroblasts (MEFs)[2]. Navitoclax (1μM ; 60 hours) accelerates apoptosis mainly by inhibiting Bcl-xL[8].

ABT-263 (Navitoclax)exhibited modest (IC50=3-8 μM) single agent potency in 8 ovarian cancer cell lines. Navitoclax(0.4μM;30h) enhanced the activation of caspase 3/7 induced by carboplatin and/or paclitaxel in Igrov-1 cells [3]. Multiple lymphoid subpopulations isolated from the thymi or BM of vavP-Bcl-2 transgenic mice were markedly more sensitive to ABT-263 (Navitoclax)[4].

ABT-263 (Navitoclax) (100 mg/kg/d;p.o;once daily for 21 days) treated a mouse model inoculated with H345 cells, and significant antitumor efficacy was observed [6]. Navitoclax with venetoclax and chemotherapy was well tolerated and had promising efficacy in patients with relapsed/refractory acute lymphoblastic leukemia or lymphoblastic lymphoma[5]. In 44 xenograft models representing 9 different histologies, ABT-263 (Navitoclax) (100 mg/kg/d;i.g; 21 days)demonstrated limited single agent in vivo activity against the PPTP's(pediatric preclinical testing program)solid tumor panels but showed significant activity against xenografts in the ALL panel [7].

References:
[1]. Tse C, Shoemaker AR, et,al. ABT-263: a potent and orally bioavailable Bcl-2 family inhibitor. Cancer Res. 2008 May 1;68(9):3421-8. doi: 10.1158/0008-5472.CAN-07-5836. PMID: 18451170.
[2]. Zhu Y, Tchkonia T, et,al.Identification of a novel senolytic agent, navitoclax, targeting the Bcl-2 family of anti-apoptotic factors. Aging Cell. 2016 Jun;15(3):428-35. doi: 10.1111/acel.12445. Epub 2016 Mar 18. PMID: 26711051; PMCID: PMC4854923.
[3]. Stamelos VA, Robinson E, et,al. Navitoclax augments the activity of carboplatin and paclitaxel combinations in ovarian cancer cells. Gynecol Oncol. 2013 Feb;128(2):377-82. doi: 10.1016/j.ygyno.2012.11.019. Epub 2012 Nov 17. PMID: 23168176.
[4]. Mérino D, Khaw SL, et,al. Bcl-2, Bcl-x(L), and Bcl-w are not equivalent targets of ABT-737 and navitoclax (ABT-263) in lymphoid and leukemic cells. Blood. 2012 Jun 14;119(24):5807-16. doi: 10.1182/blood-2011-12-400929. Epub 2012 Apr 26. PMID: 22538851; PMCID: PMC3382939.
[5]. Pullarkat VA, Lacayo NJ, et,al.Venetoclax and Navitoclax in Combination with Chemotherapy in Patients with Relapsed or Refractory Acute Lymphoblastic Leukemia and Lymphoblastic Lymphoma. Cancer Discov. 2021 Jun;11(6):1440-1453. doi: 10.1158/2159-8290.CD-20-1465. Epub 2021 Feb 16. PMID: 33593877; PMCID: PMC9533326.
[6]. Shoemaker AR, Mitten MJ, et,al. Activity of the Bcl-2 family inhibitor ABT-263 in a panel of small cell lung cancer xenograft models. Clin Cancer Res. 2008 Jun 1;14(11):3268-77. doi: 10.1158/1078-0432.CCR-07-4622. PMID: 18519752.
[7]. Lock R, Carol H, et,al. Initial testing (stage 1) of the BH3 mimetic ABT-263 by the pediatric preclinical testing program. Pediatr Blood Cancer. 2008 Jun;50(6):1181-9. doi: 10.1002/pbc.21433. PMID: 18085673.
[8].Shi J, Zhou Y, Huang HC, Mitchison TJ. Navitoclax (ABT-263) accelerates apoptosis during drug-induced mitotic arrest by antagonizing Bcl-xL. Cancer Res. 2011 Jul 1;71(13):4518-26. doi: 10.1158/0008-5472.CAN-10-4336. Epub 2011 May 5. PMID: 21546570; PMCID: PMC3129452.

Chemical Properties

Cas No. 923564-51-6 SDF
Synonyms Navitoclax,ABT-263,ABT263,ABT 263
Chemical Name (R)-4-(4-((4'-chloro-4,4-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((4-morpholino-1-(phenylthio)butan-2-yl)amino)-3-((trifluoromethyl)sulfonyl)phenyl)sulfonyl)benzamide
Canonical SMILES CC(CC1)(C)CC(CN2CCN(C3=CC=C(C(NS(C4=CC=C(N[C@@H](CSC5=CC=CC=C5)CCN6CCOCC6)C(S(C(F)(F)F)(=O)=O)=C4)(=O)=O)=O)C=C3)CC2)=C1C7=CC=C(Cl)C=C7
Formula C47H55ClF3N5O6S3 M.Wt 974.61
Solubility ≥ 48.7305mg/mL in DMSO Storage Desiccate at -20°C
General tips Please select the appropriate solvent to prepare the stock solution according to the solubility of the product in different solvents; once the solution is prepared, please store it in separate packages to avoid product failure caused by repeated freezing and thawing.Storage method and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored at -20°C, please use it within 1 month.
To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time.
Shipping Condition Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request.

Complete Stock Solution Preparation Table

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1 mg 5 mg 10 mg
1 mM 1.0261 mL 5.1303 mL 10.2605 mL
5 mM 0.2052 mL 1.0261 mL 2.0521 mL
10 mM 0.1026 mL 0.513 mL 1.0261 mL
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