923564-51-6

Basic information

• Product Name: ABT 263
• Synonyms: 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;ABT 263;Benzamide, 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)-;ABT-263,Navitoclax;Navitoclax;BenzaMide, 4-(4-((2-(4-chlorophenyl)-5,5-diMe;Navitoclax (ABT-263);(S)-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
• CAS NO: 923564-51-6
• Molecular Formula: C47H55ClF3N5O6S3
• Molecular Weight: 974.61
• Product Categories: Chiral Reagents;Inhibitors;Intermediates & Fine Chemicals;Pharmaceuticals;Sulfur & Selenium Compounds;Apis;Inhibitor
• Mol File: 923564-51-6.mol
• Article Data: 4

Chemical Properties

• Melting Point: 114-116°C
• Appearance: pale yellow solid
• Density: 1.41 g/cm³
• Refractive Index: 1.654
• Storage Temp.: -20°C Freezer, Under Inert Atmosphere
• Solubility: Soluble in DMSO (up to 25 mg/ml).
• PKA: 4.60±0.10(Predicted)
• Stability: Stable for 2 years from date of purchase as supplied. Solutions in DMSO may be stored at -20° for up to 3 months.
• CAS DataBase Reference: ABT 263(CAS DataBase Reference)
• NIST Chemistry Reference: ABT 263(923564-51-6)
• EPA Substance Registry System: ABT 263(923564-51-6)

Safety Data

• Hazardous Substances Data: 923564-51-6(Hazardous Substances Data)

Usage

Description

Different sources of media describe the Description of 923564-51-6 differently. You can refer to the following data:
1. 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.
2. ABT-263 (923564-51-6) is a potent and selective Bcl-2 family inhibitor / BH3 domain mimetic which binds to Bcl-2, Bcl-xL?and Bcl-w (Ki<1 nM). A useful tool compound which has shown interesting results in various cancer clinical trials.2?Synergizes with deoxyglucose and other agents, inducing apoptosis in cancer cells in a xenograft mouse model.3?A novel senolytic agent, inducing apoptosis preferentially in senescent cells in a cell type-restricted manner.4

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. 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.

Chemical Properties

Pale Yellow Solid

Uses

Different sources of media describe the Uses of 923564-51-6 differently. You can refer to the following data:
1. 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, respectively.
2. A novel inhibitor of antiapoptotic BCL-2 proteins; a new promising anticancer drug candidate.

Mechanism of action

ABT‐263 exerts its senolytic activity in senescent tumor cells by inhibiting BCL‐XL's interaction with BAX. ABT‐263 is a BH3 mimetic that inhibits anti‐apoptotic BCL‐2 family proteins by impeding their ability to bind pro‐apoptotic proteins, such as BAK and BAX. BCL‐2 and BCL‐XL are the primary targets of ABT‐263 in cancer cells.

References

1) Tse?et al.?(2008),?ABT-263: a potent and orally bioavailable Bcl-2 family inhibitor; Cancer Res.,?68?3421 2) Vogler?et al.?(2009),?Bcl-2 inhibitors: small molecules with a big impact on cancer therapy; Cell Death Differ.,?16?360 3) Yamaguchi?et al.?(2011),?Efficient elimination of cancer cells by deoxyglucose-ABT-263/737 combination therapy; PLoS ONE,?6(9)?e24102 4) Zhu?et al.?(2016),?Identification of a novel senolytic agent, navitoclax, targeting the Bcl-2 family of anti-apoptotic factors; Aging Cell,?15?428

InChI:InChI=1/C47H55ClF3N5O6S3/c1-46(2)20-18-42(34-8-12-37(48)13-9-34)36(31-46)32-55-22-24-56(25-23-55)39-14-10-35(11-15-39)45(57)53-65(60,61)41-16-17-43(44(30-41)64(58,59)47(49,50)51)52-38(19-21-54-26-28-62-29-27-54)33-63-40-6-4-3-5-7-40/h3-17,30,38,52H,18-29,31-33H2,1-2H3,(H,53,57)/t38-/m1/s1

Upstream product

• 1027345-12-5 [4-((R)-3-morpholin-4-yl-1-phenylsulfanyl-methyl-propylamino)-3-trifluoromethanesulfonyl]benzenesulfonamide 
• 1044598-91-5 4-(4-((4'-chloro-4,4-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)benzoic acid 

Relevant articles and documents

Profiling small molecule inhibitors against helix-receptor interactions: The Bcl-2 family inhibitor BH3I-1 potently inhibits p53/hDM2

We validate a practical methodology for the rapid profiling of small molecule inhibitors of protein-protein interactions. We find that a well known BH3 family inhibitor can potently inhibit the p53/hDM2 interaction.

An efficient synthesis of ABT-263, a novel inhibitor of antiapoptotic Bcl-2 proteins

ABT-263, a newly developed Bcl-2 inhibitor, was efficiently synthesized. The key intermediates 4-(4-{[2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-enyl] methyl}piperazin-1-yl)benzoic acid and 4-fluoro-3-[(trifluoromethyl)sulfonyl] benzenesulfonamide were eff