AZ1366   Click here for help

GtoPdb Ligand ID: 10676

Synonyms: AZ-1366 | compound 9 [PMID: 25815142]
Compound class: Synthetic organic
Comment: AZ1366 is an orally bioavailable inhibitor of the poly(ADP-ribose) polymerase (PARP) tankyrase enzymes TNKS and TNKS2 [1]. It exhibits some activity against PARP1 and PARP2. Structurally it is a nicotinamide mimetic that occupies the nicotinamide binding site of the PARP catalytic domain.
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 5
Hydrogen bond donors 3
Rotatable bonds 7
Topological polar surface area 100.13
Molecular weight 416.18
XLogP 3.66
No. Lipinski's rules broken 0
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Canonical SMILES COCCNc1ncc(c(c1)C)c1ccc(cc1)c1nc2c(CO)cccc2c(=O)[nH]1
Isomeric SMILES COCCNc1ncc(c(c1)C)c1ccc(cc1)c1nc2c(CO)cccc2c(=O)[nH]1
InChI InChI=1S/C24H24N4O3/c1-15-12-21(25-10-11-31-2)26-13-20(15)16-6-8-17(9-7-16)23-27-22-18(14-29)4-3-5-19(22)24(30)28-23/h3-9,12-13,29H,10-11,14H2,1-2H3,(H,25,26)(H,27,28,30)
1. Johannes JW, Almeida L, Barlaam B, Boriack-Sjodin PA, Casella R, Croft RA, Dishington AP, Gingipalli L, Gu C, Hawkins JL et al.. (2015)
Pyrimidinone nicotinamide mimetics as selective tankyrase and wnt pathway inhibitors suitable for in vivo pharmacology.
ACS Med Chem Lett, 6 (3): 254-9. [PMID:25815142]
2. Quackenbush KS, Bagby S, Tai WM, Messersmith WA, Schreiber A, Greene J, Kim J, Wang G, Purkey A, Pitts TM et al.. (2016)
The novel tankyrase inhibitor (AZ1366) enhances irinotecan activity in tumors that exhibit elevated tankyrase and irinotecan resistance.
Oncotarget, 7 (19): 28273-85. [PMID:27070088]
3. Scarborough HA, Helfrich BA, Casás-Selves M, Schuller AG, Grosskurth SE, Kim J, Tan AC, Chan DC, Zhang Z, Zaberezhnyy V et al.. (2017)
AZ1366: An Inhibitor of Tankyrase and the Canonical Wnt Pathway that Limits the Persistence of Non-Small Cell Lung Cancer Cells Following EGFR Inhibition.
Clin Cancer Res, 23 (6): 1531-1541. [PMID:27663586]