navitoclax   

GtoPdb Ligand ID: 8319

Synonyms: ABT 263 | ABT-263
Compound class: Synthetic organic
Comment: Navitoclax is a potent and orally active BH3 mimetic which antagonises the action of Bcl-2 family proteins Bcl-2, Bcl-xL and Bcl-w [3]. This compound is the result of medicinal chemistry effort to increase aqueous solubility of the parent compound ABT-737.
2D Structure
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Physico-chemical Properties
Hydrogen bond acceptors 11
Hydrogen bond donors 2
Rotatable bonds 18
Topological polar surface area 170.42
Molecular weight 973.3
XLogP 10.69
No. Lipinski's rules broken 3
SMILES / InChI / InChIKey
Canonical SMILES Clc1ccc(cc1)C1=C(CN2CCN(CC2)c2ccc(cc2)C(=O)NS(=O)(=O)c2ccc(c(c2)S(=O)(=O)C(F)(F)F)NC(CSc2ccccc2)CCN2CCOCC2)CC(CC1)(C)C
Isomeric SMILES Clc1ccc(cc1)C1=C(CN2CCN(CC2)c2ccc(cc2)C(=O)NS(=O)(=O)c2ccc(c(c2)S(=O)(=O)C(F)(F)F)N[C@@H](CSc2ccccc2)CCN2CCOCC2)CC(CC1)(C)C
InChI InChI=1S/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
InChI Key JLYAXFNOILIKPP-KXQOOQHDSA-N
No information available.
Summary of Clinical Use
Navitoclax is being assessed in several Phase II clinical trials for cancers including, chronic lymphocytic leukemia (CLL), metastatic/unresectable melanoma, small cell lung cancer (SCLC) and a variety of other advanced/metastatic solid tumours.
Mechanism Of Action and Pharmacodynamic Effects
BH3 antagonists hinder the interaction between antiapoptotic and proapoptotic Bcl-2 proteins which is dysregulated in cancers overexpressing antiapoptotic proteins [2]. Such antagonists should restore the activity of proapoptotic proteins, thereby leading to tumour cell death. They may even help overcome resistance to chemotherapy which is a common feature of Bcl-2-overexpressing cancers [1].