navitoclax   Click here for help

GtoPdb Ligand ID: 8319

Synonyms: ABT 263 | ABT-263
PDB Ligand
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 [6]. This compound is the result of medicinal chemistry effort to increase aqueous solubility of the parent compound ABT-737. Navitoclax has senolytic activity against senescent cells in a range of pathological conditions [2-3,5,7-9].
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2D Structure
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Physico-chemical Properties
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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
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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
References
1. Amundson SA, Myers TG, Scudiero D, Kitada S, Reed JC, Fornace Jr AJ. (2000)
An informatics approach identifying markers of chemosensitivity in human cancer cell lines.
Cancer Res, 60 (21): 6101-10. [PMID:11085534]
2. Budamagunta V, Kumar A, Rani A, Manohar Sindhu S, Yang Y, Zhou D, Foster TC. (2024)
Senolytic treatment alleviates doxorubicin-induced chemobrain.
Aging Cell, 23 (2): e14037. [PMID:38225896]
3. Escriche-Navarro B, Garrido E, Sancenón F, García-Fernández A, Martínez-Máñez R. (2024)
A navitoclax-loaded nanodevice targeting matrix metalloproteinase-3 for the selective elimination of senescent cells.
Acta Biomater, 176: 405-416. [PMID:38185231]
4. Green DR, Evan GI. (2002)
A matter of life and death.
Cancer Cell, 1 (1): 19-30. [PMID:12086884]
5. Maggiorani D, Le O, Lisi V, Landais S, Moquin-Beaudry G, Lavallée VP, Decaluwe H, Beauséjour C. (2024)
Senescence drives immunotherapy resistance by inducing an immunosuppressive tumor microenvironment.
Nat Commun, 15 (1): 2435. [PMID:38499573]
6. Park CM, Bruncko M, Adickes J, Bauch J, Ding H, Kunzer A, Marsh KC, Nimmer P, Shoemaker AR, Song X et al.. (2008)
Discovery of an orally bioavailable small molecule inhibitor of prosurvival B-cell lymphoma 2 proteins.
J Med Chem, 51 (21): 6902-15. [PMID:18841882]
7. Ro DH, Cho GH, Kim JY, Min SK, Yang HR, Park HJ, Wang SY, Kim YJ, Lee MC, Bae HC et al.. (2024)
Selective targeting of dipeptidyl-peptidase 4 (DPP-4) positive senescent chondrocyte ameliorates osteoarthritis progression.
Aging Cell, 23 (7): e14161. [PMID:38556837]
8. Sato S, Ogawa Y, Shimizu E, Asai K, Okazaki T, Rusch R, Hirayama M, Shimmura S, Negishi K, Tsubota K. (2024)
Cellular senescence promotes meibomian gland dysfunction in a chronic graft-versus-host disease mouse model.
Ocul Surf, 32: 198-210. [PMID:38499288]
9. Zheng H, Liu M, Shi S, Huang H, Yang X, Luo Z, Song Y, Xu Q, Li T, Xue L et al.. (2024)
MAP4K4 and WT1 mediate SOX6-induced cellular senescence by synergistically activating the ATF2-TGFβ2-Smad2/3 signaling pathway in cervical cancer.
Mol Oncol, [Epub ahead of print]. [PMID:38383842]