| Identification | Back Directory | [Name]
AZ0108
(AZ 0108) | [CAS]
1825345-52-5 | [Synonyms]
AZ0108
AZ0108
(AZ 0108)
1(2H)-Phthalazinone, 4-[[3-[[(6S)-3-(1,1-difluoroethyl)-5,6-dihydro-6-methyl-1,2,4-triazolo[4,3-a]pyrazin-7(8H)-yl]carbonyl]phenyl]difluoromethyl]- | [Molecular Formula]
C24H20F4N6O2 | [MOL File]
1825345-52-5.mol | [Molecular Weight]
500.45 |
| Chemical Properties | Back Directory | [density ]
1.50±0.1 g/cm3(Predicted) | [storage temp. ]
-10 to -25°C | [solubility ]
DMSO: 2mg/mL, clear | [form ]
powder | [pka]
11.37±0.40(Predicted) | [color ]
white to beige | [SMILES]
FC(C1=CC=CC(C(N2[C@@H](C)CN3C(C2)=NN=C3C(F)(F)C)=O)=C1)(F)C(C4=CC=CC=C45)=NNC5=O |
| Hazard Information | Back Directory | [Uses]
AZ0108 is an inhibitor for poly ADP-ribose polymerase (PARP), which inhibits PARP1, PARP2, PARP3, PARP6, TNKS1, TNKS2, with IC50s of <0.03, <0.03, 2.8, 0.083, 3.2, >3 μM, respectively. AZ0108 prevents centrosome clustering with an EC50 of 0.053 μM, and exhibits cytotoxicity in cell OCI-LY-19 with GI50 of 0.017 μM. AZ0108 exhibits good in vivo pharmacokinetic characters in rat/mouse models[1]. | [Biological Activity]
Inhibitor of Poly (ADP-ribose) polymerase PARP12and 6.
AZ0108 is an inhibitor of Poly (ADP-ribose) polymerase PARP12and 6 with approximately 100-fold selectivity against PARP3 and TNKS1. It was shown to block centrosome clustering in HeLa cells with an EC50 value of 53 nM and kill a DLBCL lymphoma cancer cell line with a GI50 value of 17 nM. AZ0108 induces replication stress in tumorigenic cells. | [IC 50]
PARP1: 0.03 μM (IC50); PARP2: 0.03 μM (IC50); PARP6: 0.083 μM (IC50); PARP3: 2.8 μM (IC50); TNKS1: 3.2 μM (IC50) | [References]
[1] Johannes JW, et al., Discovery of AZ0108, an orally bioavailable phthalazinone PARP inhibitor that blocks centrosome clustering. Bioorg Med Chem Lett. 2015 Dec 15;25(24):5743-7. DOI:10.1016/j.bmcl.2015.10.079 |
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