A3007-5mg | ABT-263 (Navitoclax) [923564-51-6] Clinisciences

ABT-263 is an orally sellecitive inhibitor of B-cell leukemia 2 (Bcl-2) family of proteins with potential antineoplastic activity. ABT-263 is a small molecular with the formula of C47H55ClF3N5O6S3 and Molecular Weight of 974. As a Bad-like Bh3 minetic, ABT-263 binds to Bcl-2 family proteins Bcl-2, Bcl-xl and Bcl-w, disrupts the interaction between Bcl-2/Bcl-xl /Bcl-w and pro-apoptotic proteins such as Bim, Bad and Bak, which trigger the caspases-initiated cell death pathway to induce apoptosis.

References:

1. Tse et al., ABT-263: A Potent and Orally Bioavailable Bcl-2 Family Inhibitor. Cancer Res. 2008, 68, 3421-3428.

2. Shoemaker 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, 14, 3268-3277

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Storage	Desiccate at -20°C
M.Wt	974.61
Cas No.	923564-51-6
Formula	C₄₇H₅₅ClF₃N₅O₆S₃
Synonyms	Navitoclax,ABT-263,ABT263,ABT 263
Solubility	≥48.73 mg/mL in DMSO; insoluble in EtOH; insoluble in H2O
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
SDF	Download SDF
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
Shipping Condition	Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice.
General tips	We do not recommend long-term storage for the solution, please use it up soon.

Cell experiment:[1]
Cell lines	Murine DO11.10 T-hybridoma cells expressing murine Bcl-2, Bcl-xL and Bcl-w proteins
Preparation method	The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while.Stock solution can be stored below -20°C for several months.
Reaction Conditions	None specifc suggestion
Applications	ABT-263 is an antitumor effector in preclinical and early clinical studies. It binds to Bcl-2, Bcl-xL, and Bcl-w in vitro, but only targets Bcl-2 in vivo. In human non-Hodgkin lymphomas, high expression of Bcl-2 sensitized to ABT-263 elevated proapoptotic Bim.
Animal experiment:[2]
Animal models	Immune-deficient NOD/SCID or NOD/SCID, ILγ receptor negative mice
Dosage form	Orally taken at 100 mg/kg/day for 21 days
Applications	ABT-263 can largely inhibited the activity of patient-derived pediatric acute lymphoblastic leukemia xenograft. ABT-263 sensitivity was correlated with low MCL1 mRNA expression levels. BH3 profiling revealed that resistance to ABT-263 correlated with mitochondrial priming by NOXA peptide.
Other notes	Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.
References: 1. Mérino D1, Khaw SL, Glaser SP 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. 2. Suryani S, Carol H, Chonghaile TN et al. Cell and Molecular Determinants of In Vivo Efficacy of the BH3 Mimetic ABT-263 against Pediatric Acute Lymphoblastic Leukemia Xenografts. Clin Cancer Res. 2014 Jul 10.

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.
Targets	Bcl-xL	Bcl-2	Bcl-w
IC50	≤ 0.5 nM (K_i)	≤1 nM (K_i)	≤ 1 nM (K_i)