ABT-263 (Navitoclax)

Catalog No.S1001

ABT-263 (Navitoclax) is a potent inhibitor of Bcl-xL, Bcl-2 and Bcl-w with Ki of ≤ 0.5 nM, ≤1 nM and ≤1 nM in cell-free assays, but binds more weakly to Mcl-1 and A1. Phase 2.

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ABT-263 (Navitoclax) Chemical Structure

ABT-263 (Navitoclax) Chemical Structure
Molecular Weight: 974.61

Validation & Quality Control

Cited by 36 publications:

13 customer reviews :

Quality Control & MSDS

Related Compound Libraries

ABT-263 (Navitoclax) is available in the following compound libraries:

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Product Information

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  • Research Area
  • Inhibition Profile

Product Description

Biological Activity

Description ABT-263 (Navitoclax) is a potent inhibitor of Bcl-xL, Bcl-2 and Bcl-w with Ki of ≤ 0.5 nM, ≤1 nM and ≤1 nM in cell-free assays, but binds more weakly to Mcl-1 and A1. Phase 2.
Targets Bcl-xL [1]
(Cell-free assay)
Bcl-2 [1]
(Cell-free assay)
Bcl-w [1]
(Cell-free assay)
A1 [1]
(Cell-free assay)
Mcl-1 [1]
(Cell-free assay)
IC50 <=0.5 nM(Ki) <=1 nM(Ki) <=1 nM(Ki) 354 nM(Ki) 550 nM(Ki)
In vitro ABT-263 is structurally related to ABT-737; it is a disruptor of Bcl-2/Bcl-xL interactions with pro-apoptotic proteins. Overexpression of the prosurvival Bcl-2 family members is commonly associated with tumor maintenance, progression, and chemoresistance. [1] ABT-263 displays the protection afforded by overexpression of Bcl-2 or Bcl-xL with EC50 values of 60 nM and 20 nM, respectively. [1] A wide range of cellular activity is observed with ABT-263 having a 50% growth inhibition (EC50) of 110 nM against the most sensitive line (H146), whereas its activity in the least sensitive line (H82) results in an EC50 at 22 μM. All four cell lines with EC50 values of <400 nM (H146, H889, H1963, and H1417) are also highly sensitive to ABT-737, and the two most resistant lines (H1048 and H82) are similarly resistant to ABT-263. [2]
Cell Data
Cell LinesAssay TypeConcentrationIncubation TimeFormulationActivity DescriptionPMID
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SW1463NHXKUphIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=NXrzSXp1UUN3ME20OE46QTdzIN88US=>MmTmV2FPT0WU
DSH1NXHlSpN2T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=NIDjW3VKSzVyPUS1MlAxOzNizszNM4jDdHNCVkeHUh?=
MCF7MVHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?MmjnTWM2OD12NT61NFUyKM7:TR?=MXLTRW5ITVJ?
K5M3LQZmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7MWjJR|UxRTR3Lkm0NFUh|ryPNYS5Ool3W0GQR1XS
NCI-H358M4rjeWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7M2T5N2lEPTB;NEeuNlE2KM7:TR?=M3u1cHNCVkeHUh?=
NCI-H2030NYHaPG5UT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=MlH6TWM2OD12Nz6yN|c1KM7:TR?=NYXwcppPW0GQR1XS
SW948M4jBW2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7M1[yT2lEPTB;NEeuOFY1KM7:TR?=MVPTRW5ITVJ?
BALL-1MlXhS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?M1niVmlEPTB;NEeuOlE3QCEQvF2=NWjxfIxmW0GQR1XS
TE-9NFLHdHZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=M{DtW2lEPTB;NEeuPVU5OSEQvF2=MoHHV2FPT0WU
SK-N-FIMnK2S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?M1v4O2lEPTB;NEiuNFM2QCEQvF2=M3;WUXNCVkeHUh?=
KALS-1NYD4UYJyT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=MnjyTWM2OD12OD6xNlg6KM7:TR?=NGjVcnRUSU6JRWK=
HO-1-N-1M3Xq[Gdzd3e2aDDJcohq[mm2aX;uJGF{e2G7NH36NXFKSzVyPUS4Mlc1PDVizszNMY\TRW5ITVJ?
NCI-H2452NEjqUphIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=MoH5TWM2OD12OT6xNVUzKM7:TR?=M1vYeXNCVkeHUh?=
OC-314M4Dlcmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7NFiyZ3JKSzVyPUS5MlY5OzRizszNMW\TRW5ITVJ?

... Click to View More Cell Line Experimental Data

In vivo When ABT-263 is administered at 100 mg/kg/day in the H345 xenograft model, significant antitumor efficacy is observed with 80% TGI and 20% of treated tumors indicating at least a 50% reduction in tumor volume. [2] Oral administration of ABT-263 alone causes complete tumor regressions in xenograft models of small-cell lung cancer and acute lymphoblastic leukemia. In xenograft models of aggressive B-cell lymphoma and multiple myeloma where ABT-263 displays modest or no single agent activity, it significantly enhances the efficacy of clinically relevant therapeutic regimens. [2]
Features

Protocol(Only for Reference)

Kinase Assay:

[1]

Affinity determination Binding affinities (Ki or IC50) of ABT-263 against different isoforms of Bcl-2 family are determined with competitive fluorescence polarization assays. The following peptide probe/protein pairs are used: 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). Binding affinities for Bcl-xL are also determined using a time-resolved fluorescence resonance energy transfer assay. Bcl-xL (1 nM, His tagged) is mixed with 200 nM f-Bak, 1 nM Tb-labeled anti-His antibody, and ABT-263 at room temperature for 30 min. Fluorescence is measured on an Envision plate reader using a 340/35 nm excitation filter and 520/525 (f-Bak) and 495/510 nm (Tb-labeled anti-His antibody) emission filters.

Cell Assay:

[1]

Cell lines SCLC cell lines
Concentrations 0-1 μM
Incubation Time 48 hours
Method

Human tumor cell lines SCLC cell lines are maintained at 37 °C containing 5% CO2. SCLC cell lines are cultured in RPMI 1640 with 10% fetal bovine serum (FBS), 1% sodium pyruvate, 25 mM HEPES, 4.5 g/L glucose, and 1% penicillin/streptomycin. Leukemia and lymphoma cell lines are cultured in RPMI 1640 supplemented with 10% FBS and 1% penicillin/streptomycin. Cells (1-5×10 4) are treated by ABT-263 for 48 hours in 96-well culture plates in a final volume of 100 μL and cytotoxicity is assessed with the CellTiter Glo assay. In vitro cyto toxicity of ABT-263 is assayed.

Animal Study:

[1]

Animal Models C.B.-17 scid-bg or C.B.-17 scid mice
Formulation Formulated in 10% ethanol, 30% polyethylene glycol 400, and 60% Phosal 50 PG
Dosages 100 mg/kg/d
Administration Administered via p.o.

Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)

SpeciesMouseRatRabbitGuinea pigHamsterDog
Weight (kg)0.020.151.80.40.0810
Body Surface Area (m2)0.0070.0250.150.050.020.5
Km factor36128520
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.

Rat dose (mg/kg) = mouse dose (22.4 mg/kg) ×  mouse Km(3)  = 11.2 mg/kg
rat Km(6)
1

References

[1] Tse C, et al. Cancer Res. 2008, 68(9), 3421-3428.

[2] Shoemaker AR, et al. Clin Cancer Res, 2008, 14(11), 3268-3277.

Clinical Trial Information( data from http://clinicaltrials.gov, updated on 2016-07-30)

NCT Number Recruitment Conditions Sponsor
/Collaborators
Start Date Phases
NCT02520778 Recruiting Recurrent Non-Small Cell Lung Carcinoma|Stage IIIA Non-Small Cell Lung Cancer|Stage IIIB Non-Small Cell Lung Cancer|Stage IV Non-Small Cell Lung Ca  ...more Recurrent Non-Small Cell Lung Carcinoma|Stage IIIA Non-Small Cell Lung Cancer|Stage IIIB Non-Small Cell Lung Cancer|Stage IV Non-Small Cell Lung Cancer National Cancer Institute (NCI) March 2016 Phase 1
NCT02591095 Recruiting Platinum-resistant or Refractory Ovarian Cancer Centre Francois Baclesse|ARCAGY/ GINECO GROUP|French Canc  ...more Centre Francois Baclesse|ARCAGY/ GINECO GROUP|French Cancer Research Hospital Program January 2016 Phase 2
NCT02143401 Recruiting Recurrent Hepatocellular Carcinoma|Solid Neoplasm|Stage IV Hepatocellular Carcinoma National Cancer Institute (NCI) November 2014 Phase 1
NCT02079740 Suspended Recurrent Colorectal Carcinoma|Recurrent Lung Carcinoma|Recurrent Pancreatic Carcinoma|Solid Neoplasm|Stage III Lung Cancer|Stage III Pancreatic Ca  ...more Recurrent Colorectal Carcinoma|Recurrent Lung Carcinoma|Recurrent Pancreatic Carcinoma|Solid Neoplasm|Stage III Lung Cancer|Stage III Pancreatic Cancer|Stage IIIA Colorectal Cancer|Stage IIIB Colorectal Cancer|Stage IIIC Colorectal Cancer|Stage IV Lung Cancer|Stage IV Pancreatic Cancer|Stage IVA Colorectal Cancer|Stage IVB Colorectal Cancer National Cancer Institute (NCI) March 2014 Phase 1|Phase 2
NCT01989585 Recruiting Metastatic Melanoma|Recurrent Melanoma|Solid Neoplasm|Stage IIIA Skin Melanoma|Stage IIIB Skin Melanoma|Stage IIIC Skin Melanoma|Stage IV Skin Mela  ...more Metastatic Melanoma|Recurrent Melanoma|Solid Neoplasm|Stage IIIA Skin Melanoma|Stage IIIB Skin Melanoma|Stage IIIC Skin Melanoma|Stage IV Skin Melanoma National Cancer Institute (NCI) October 2013 Phase 1|Phase 2

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Chemical Information

Download ABT-263 (Navitoclax) SDF
Molecular Weight (MW) 974.61
Formula

C47H55ClF3N5O6S3

CAS No. 923564-51-6
Storage 3 years -20℃powder
6 months-80℃in solvent
Synonyms N/A
Solubility (25°C) * In vitro DMSO 100 mg/mL (102.6 mM)
Water <1 mg/mL (<1 mM)
Ethanol <1 mg/mL (<1 mM)
In vivo
* <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.
Chemical Name 4-​[4-​[[2-​(4-​chlorophenyl)​-​5,​5-​dimethyl-​1-​cyclohexen-​1-​yl]​methyl]​-​1-​piperazinyl]​-​N-​[[4-​[[(1R)​-​3-​(4-​morpholinyl)​-​1-​[(phenylthio)​methyl]​propyl]​amino]​-​3-​[(trifluoromethyl)​sulfonyl]​phenyl]​sulfonyl]​-benzamide

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Tel: +1-832-582-8158 Ext:3

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