AZ0108

AZ0108 : NAD+ competitive inhibitor of PARP1, PARP2, PARP6

Structure

SERP Rating

In Cells

(3 ratings)

In Model Organisms

(3 ratings)

note: The Chemical Probes Portal only endorses compounds as chemical probes for use as specific and selective modulators of the proposed target if they receive three or more (3-4) stars.

Information

PARP1
PARP2
PARP6

NAD+ competitive inhibitor

Probe Availability:

MedKoo

In Vitro Validations

Uniprot ID: P09874

Target Class: Other post-translational modification

Target SubClass: PARP

Potency: IC50

Potency Value: <30nM

Potency Assay: All PARP enzyme assays were done by following the BPS PARP assay kit protocols.

PDB ID for probe-target interaction (3D structure): --

Structure-activity relationship: Yes

Target aliases:

Poly [ADP-ribose] polymerase 1, PPOL, ADPRT, PARP1 ...

DOI Reference: 10.1016/j.bmcl.2015.10.079

In Cell Validations

In Vivo Data

Off-Target Selectivity Assesments

Potency end-point : IC50 PARP3 2.8 uM, TNKS 2.3 uM, TNKS2 <3 uM

Potency assay (off target): AZ0108 inhibits PARPs 1, 2, and 6 with approximately 100-fold selectivity against PARP3 and TNKS1, and it is not active in a DLD-1 Wnt luciferase reporter assay.

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SERP ratings and comments

SERP Ratings

In Cell Rating

In Model Organisms

SERP Comments:

Probe use in model organism: A further publication concerning in-depth details of the biological effects was announced in the key reference paper (reference 23).

(last updated: 12 Aug 2016 )

SERP Ratings

In Cell Rating

In Model Organisms

SERP Comments:

AZ0108 potently declusters centrosomes in HeLa cells (EC₅₀ = 53 nM) and kills a DLBCL cell line (GI50 = 17 nM). More studies are needed to determine how useful this probe is, including linking the phenotype and cell death in the same cell line.

(last updated: 8 Sept 2016 )

SERP Ratings

In Cell Rating

In Model Organisms

SERP Comments:

AZ0108 is also reported to have a GI₅₀ of 0.017 uM in the DLBCL cell line OCI-LY-19. Although this compound seems promising, additional studies are needed to determine how useful it will be as a probe. I would have like to see some images of cells that no longer had a multi-polar spindle phenotype.

(last updated: 8 Sept 2016 )

SERP Comments:

AZ0108 is a more selective PARP enzyme inhibitor (i.e., PARP 1, 2, and 6) compared with other more broad-acting PARP inhibitors. AZ0108 has cellular effects.

(last updated: 12 Sept 2016 )

Portal Comments

AZ0108 is a more selective PARP enzyme inhibitor (i.e., PARP 1, 2, and 6) compared with other more broad-acting PARP inhibitors. AZ0108 has cellular effects.

(last updated: 12 Sept 2016)