923564-51-6 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
Check Digit Verification of cas no
The CAS Registry Mumber 923564-51-6 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 9,2,3,5,6 and 4 respectively; the second part has 2 digits, 5 and 1 respectively.
Calculate Digit Verification of CAS Registry Number 923564-51:
(8*9)+(7*2)+(6*3)+(5*5)+(4*6)+(3*4)+(2*5)+(1*1)=176
176 % 10 = 6
So 923564-51-6 is a valid CAS Registry Number.
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
923564-51-6Relevant articles and documents
Profiling small molecule inhibitors against helix-receptor interactions: The Bcl-2 family inhibitor BH3I-1 potently inhibits p53/hDM2
Porter, Jason R.,Helmers, Mark R.,Wang, Ping,Furman, Jennifer L.,Joy, Stephen T.,Arora, Paramjit S.,Ghosh, Indraneel
supporting information; experimental part, p. 8020 - 8022 (2011/01/03)
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
Wang, Guangjun,Zhang, Hushan,Zhou, Jing,Ha, Chengyong,Pei, Duanqing,Ding, Ke
experimental part, p. 2398 - 2404 (2009/04/07)
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