Veliparib

Catalytic inhibitor, PARP-DNA complex trapping of PARP1, PARP2

Structure

Information

Protein target names: PARP1, PARP2

Mechanism of action: Catalytic inhibitor, PARP-DNA complex trapping

In Vitro Validations

Uniprot ID: P09874
Target Class: Other post-translational modification
Target SubClass: PARP
Potency: Ki
Potency Value: 5.2 nM
Potency Assay: Biochemical Assay
PDB ID for probe-target interaction (3D structure): --
Structure-activity relationship: Yes
Target aliases:
Poly [ADP-ribose] polymerase 1, PPOL, ADPRT, PARP1 ...

DOI Reference: 10.1021/acs.jmedchem.6b00990

Uniprot ID: P09874
Target Class: Other post-translational modification
Target SubClass: PARP
Potency: IC 50
Potency Value: 3.3 nM
Potency Assay: ADP ribosylation assays, PARP1 (full length)
PDB ID for probe-target interaction (3D structure): --
Target aliases:
Poly [ADP-ribose] polymerase 1, PPOL, ADPRT, PARP1 ...

DOI Reference: 10.1021/acs.jmedchem.6b00990

In Cell Validations

In Vivo Data

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SERP ratings and comments


SERP Ratings

In Cell Rating
In Model Organisms

Comments:

Veliparib is a PARP 1/2 inhibitor. This agent is an excellent tool to study PARP inhibition in both the cellular and in vivo setting. However, an important study about the mechanism of these probes appeared in 2012 (Murai et al., Cancer Res. 2012, 72, 5588-5599). In this study, the authors examined the ability of niraparib, olaparib and veliparib to trap PARP1/2 enzymes at the site of DNA damage as opposed to examining merely their activity as inhibitors of the catalytic function of the enzyme. The authors found that the cellular toxicity tracked with the trapping potential (which was different for each drug) rather than each drugs catalytic efficiency (which was similar for each drug). The ranking of each drug for trapping efficiency was found to be niraparib > olaparib >> veliparib. Investigators should thoroughly evaluate their needs when choosing the appropriate PARP inhibitor based upon this altered mechanistic insight.

(last updated: 1 Aug 2016 )

SERP Ratings

In Cell Rating
In Model Organisms

Comments:

Velaparib is not overly potent in vivo as a a single agent but potentiates both chemo- and radiotherapy. Like other PARP inhibitors, veliparib is a potent inhibitor of PARP1 and 2 but not the other 15 family members. Critically, velparib appears to inhibit PARP as an inhibitor of catalytic function and does not enhance PARP trapping at the site of DNA damage. Given this, veliparib is strongly recommended for the deconvolution of the catalytic roles of PARP in in vitro experiments.

(last updated: 9 Sept 2016 )

SERP Ratings

In Cell Rating

Comments:

Veliparib is a potent dual PARP1/2 inhibitor. It is highly recommended for studying the function of these targets in vitro. Veliparib has also shown utility in in vivo studies and even some degree of CNS penetrance. 

(last updated: 17 Jan 2017 )

SERP Ratings

Comments:

Veliparib is a PARP1/2 inhibitor with selectivity sufficient for cellular work to interrogate PARP1/2. While target engagement has been shown in vivo at modest doses, the lack of receptor profiling limits my recommendation for Veliparib to be used as an in vivo probe.

(last updated: 18 Jan 2017 )