ABT 263

Base Information

• Chemical Name: ABT 263
• CAS No.: 923564-51-6
• Molecular Formula: C₄₇H₅₅ClF₃N₅O₆S₃
• Molecular Weight: 974.63
• Hs Code.: 29339900
• Mol file: 923564-51-6.mol

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

Chemical Property of ABT 263

Chemical Property:

• Appearance/Colour: pale yellow solid
• Melting Point: 114-116 °C
• Refractive Index: 1.654
• PKA: 4.60±0.10(Predicted)
• PSA: 170.42000
• Density: 1.41 g/cm³
• LogP: 11.39950
• Storage Temp.: -20°C Freezer, Under Inert Atmosphere
• Solubility.: Soluble in DMSO (up to 25 mg/ml).

Purity/Quality:

99% ^*data from raw suppliers

ABT263 ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• 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. 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
• Uses: 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. A novel inhibitor of antiapoptotic BCL-2 proteins; a new promising anticancer drug candidate.

Technology Process of ABT 263

There total 1 articles about ABT 263 which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 84.0%

[4-((R)-3-morpholin-4-yl-1-phenylsulfanyl-methyl-propylamino)-3-trifluoromethanesulfonyl]benzenesulfonamide (1027345-12-5) + 4-(4-((4'-chloro-4,4-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)benzoic acid (1044598-91-5) → navitoclax (923564-51-6)

Guidance literature:

With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In dichloromethane; at 20 ℃; for 36h;

DOI:10.1055/s-2008-1067129

upstream raw materials:

[4-((R)-3-morpholin-4-yl-1-phenylsulfanyl-methyl-propylamino)-3-trifluoromethanesulfonyl]benzenesulfonamide

4-(4-((4'-chloro-4,4-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)benzoic acid

Refernces

Structure-guided design of a series of MCL-1 inhibitors with high affinity and selectivity

10.1021/jm501258m

The study focuses on the development of small molecule inhibitors targeting MCL-1, a BCL-2 family protein implicated in cancer progression and survival. The researchers started with a high-throughput screening (HTS) hit compound 1, which had micromolar affinity for MCL-1. Through iterative cycles of structure-guided design and co-crystal structure analysis, they progressed to more potent analogs. Key chemicals involved include compound 5, which showed a ten-fold increase in binding affinity due to the addition of a 4-(1-naphthoxypropyl) group, and compound 14, which further improved affinity with an N(1)-tethered morpholinoethyl substituent. The most advanced compound, 30b, demonstrated sub-nanomolar affinity for MCL-1 and selectivity over other BCL-2 family proteins, as well as activity in MCL-1-dependent human tumor cell lines, such as H929 and BxPC-3. This compound also showed synergy with navitoclax in overcoming resistance in cancer cells. The study highlights the importance of structure-based drug design in optimizing MCL-1 inhibitors for potential cancer therapy.