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AZ6102 | AZ6102 : NAD+ competitive inhibitor of TNKS, TNKS2
RATINGS:
Cellular Use: (3 reviews)

In Model Organisms: (2 reviews)
Probe Summary
Selectivity
Potency
In Vivo
Control Compounds
Chemical Information
References
Vendors
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Probe Summary

Targets Biochemical/Biophysical Potency Cellular Potency
TNKS
  • IC 50:3 nM
  • IC 50:100 nM
  • IC 50:0.005 uM
TNKS2
  • IC 50:1 nM
  • IC 50:0.6 nM
  • IC50:0.005 uM
NAD+ competitive
50-500 nM

Selectivity

In Vitro Selectivity Assessment

Potency: IC50 - PARP1 2 uM, PARP2 0.5 uM, PARP6 >5 uM

Potency Assay Off-Target:
SPA or BPS PARP assay kit. In in vitro ADP ribosylation assays, AZ-6102 was selective for TNKS1/2 ov ...
Selectivity Assessment Description:
SPA or BPS PARP assay kit. In in vitro ADP ribosylation assays, AZ-6102 was selective for TNKS1/2 ov ...

Potency
Cellular
In Vitro

TNKS

Mode of Action: NAD+ competitive

Structure-Activity-Relationship data available? Yes

DOI Reference: 10.1021/acs.jmedchem.6b00990

TNKS2

Mode of Action: NAD+ competitive

Structure-Activity-Relationship data available? Yes

DOI Reference: 10.1021/acs.jmedchem.6b00990

In Vivo Validations

Rat, Mouse
Dose: 25 mg/kg IV (mouse)
Route of delivery: Intravenous, Oral
Plasma half life: 5.7 hr (rat IV), 4.3 hr (mouse IV)
Systemic clearance: 11 mL/min•kg (rat IV), 24 mL/min•kg (mouse IV)

DOI Reference: 10.1021/acs.jmedchem.6b00990

Orthogonal Probes def

XAV939
JW55

Chemical Information

Molecular Formula C25H28N6O
SMILEs Cc1cc(N2C[C@H](C)N[C@H](C)C2)ncc1-c1ccc(-c2nc(=O)c3ccn(C)c3[nH]2)cc1
InChI InChI=1S/C25H28N6O/c1-15-11-22(31-13-16(2)27-17(3)14-31)26-12-21(15)18-5-7-19(8-6-18)23-28-24-20(25(32)29-23)9-10-30(24)4/h5-12,16-17,27H,13-14H2,1-4H3,(H,28,29,32)/t16-,17+
Molecular weight 428.23 Da
AlogP 3.4856200000000017
HBond acceptors 7
HBond donors 2
Atoms 60

References

Publications

Cross References

GDSC2

Vendors

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Expert Reviews

by SERP
(on 12 Aug 2016)
Cellular Use Rating
AZ6102 shows good inhibition of TNK1/2 with selectivity against other related enzymes of the PARP family. Data about other potential off targets (e.g., other NAD+-dependent enzymes or protein kinases)...
by SERP
(on 20 Jan 2017)
Cellular Use Rating
In Model Organisms
(The reviewer did not leave any public comments)
by SERP
(on 11 Apr 2017)
Cellular Use Rating
In Model Organisms
Although two independent papers report that this is a potent (low nM) TNKS2 inhibitor, they report significant discrepancies in TNKS1 inhibition (3 and 100 nM). The oral bioavailability is modest (F...
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