PARP
Signaling Pathway Map
Research Area
Inhibitory Selectivity
Isoform-specific Inhibitors
PARP Products
| Catalog No. | Information | Product Use Citations | Product Validations |
|---|---|---|---|
| S1060 |
Olaparib (AZD2281)Olaparib (AZD2281, KU0059436) is a selective inhibitor of PARP1/2 with IC50 of 5 nM/1 nM in cell-free assays, 300-times less effective against tankyrase-1. Olaparib induces significant autophagy that is associated with mitophagy in cells with BRCA mutations. |
Role of PARP and BER in the synergy between PTX and GMX in A549 cells. A) Cells were pre-treated +/- 1 uM olaparib (2h) then sequentially +/- 150nM PTX (24h) then +/- GMX 12nM (48h). Cells were harvested for (left) NAD+ quantification by LC-MS/MS (mean +/-SD of quadruplicates) or (right) viability by CellTiter-Glo (mean +/-SD of duplicates) B) PAR modification of proteins and γ-H2AX levels were measured in extracts treated as in A) by western blotting.
|
|
| S1004 |
Veliparib (ABT-888)Veliparib (ABT-888, NSC 737664) is a potent inhibitor of PARP1 and PARP2 with Ki of 5.2 nM and 2.9 nM in cell-free assays, respectively. It is inactive to SIRT2. Veliparib increases autophagy and apoptosis. Phase 3. |
Number of foci detected using laser confocal microscopy and fluorescent Fluor 647 anti-H2A.X-phosphorylated (Ser139) antibody. Double-stranded breaks (red) are clearly augmented in cells incubated with 500 nmol/l of ABT-888 and 500 nmol/l of AZD-2281 compared with PBS and 1% dimethyl sulfoxide controls. Image analysis was performed using ImageJ and the ‘analyze particle’ function. |
|
| S1180 |
XAV-939XAV-939 (NVP-XAV939) selectively inhibits Wnt/β-catenin-mediated transcription through tankyrase1/2 inhibition with IC50 of 11 nM/4 nM in cell-free assays, regulates axin levels and does not affect CRE, NF-κB or TGF-β. |
Fluorescence microscopy of pSuper or Cdo shRNA expressing P19 cells at ITS1 immunostained withβ-tubulin III antibodies. Size bar=100 um. P19/control or P19/Cdo shRNA cells were treated with DMSO or XAV939 in the differentiation medium for 72 h followed by immunostaining.
|
|
| S1098 |
Rucaparib (AG-014699) phosphateRucaparib (AG-014699, PF-01367338) is an inhibitor of PARP with Ki of 1.4 nM for PARP1 in a cell-free assay, also showing binding affinity to eight other PARP domains. Phase 3. |
For anchorage dependent clonogenic assays, HER2+ breast cancer BT474 cells were seeded at low density in 6-well plates and allowed to adhere overnight. The next day, olaparib and rucaparib were added at the indicated concentrations. Media and drugs were replenished every three days. After 10-15 days, depending on cell proliferation rate, cells were fixed and stained with crystal violet. Images and graphs indicate the results compared to control condition. Data are mean ± S.D. n.s.: non-significant, ∗p < 0.05, ∗∗p < 0.01, ∗∗∗p < 0.001.
|
|
| S1087 |
Iniparib (BSI-201)Iniparib (BSI-201, NSC-746045, IND-71677) is a PARP1 inhibitor with demonstrated effectiveness in triple-negative breast cancer (TNBC). Phase 3. |
Immunoblot analysis of
PARylation after treatment with various PARP
inhibitors.The asterisk indicates
a nonspecific band.
|
|
| S8876New |
RK-287107RK-287107 is a novel, potent and selective tankyrase inhibitor with antitumor activity. RK-287107 inhibits tankyrase-1 and tankyrase-2 in vitro with IC50 of 14.3 nM and 10.6 nM. |
||
| S6739New |
MN 64MN-64 is a potent inhibitor of TNKS1 and TNKS2 with IC50 value of 6 and 72 nM, respectively. |
||
| S7048 |
Talazoparib (BMN 673)Talazoparib (BMN 673) is a novel PARP inhibitor with IC50 of 0.57 nM for PARP1 in a cell-free assay. It is also a potent inhibitor of PARP-2, but does not inhibit PARG and is highly sensitive to PTEN mutation. Phase 3. |
Western blot assessment of effects on PAR, PARP, and dsDNA breaks mediated by IMMU-132 plus PARPi in TNBC tumor lines. Cells were plated overnight in 6-well plates before the addition of chemotherapeutics. After a 24-hour incubation, cells were harvested and cell lysates resolved and transferred for Western analysis as described in Materials and Methods. PAR and FL-PARP levels were determined on the same gel. Assessment of dsDNA breaks (p-H2A.X) was calculated as ratios relative to untreated control (Unt) normalized to b-actin protein loading control (Dp-H2A.X). B, HCC1806 cells exposed to rucaparib (Ruc) and IMMU-132 or to (C) talazoparib (Tala) and IMMU-132. |
|
| S2178 |
AG-14361AG14361 is a potent inhibitor of PARP1 with Ki of <5 nM in a cell-free assay. It is at least 1000-fold more potent than the benzamides. |
Immunoblot analysis of PARylation after treatment with various PARP inhibitors.The asterisk indicates a nonspecific band. |
|
| S1132 |
INO-1001 (3-Aminobenzamide)INO-1001 (3-ABA , 3-Amino Benzamide, 3-AB) is a potent inhibitor of PARP with IC50 of <50 nM in CHO cells and a mediator of oxidant-induced myocyte dysfunction during reperfusion. Phase 2. |
Effect of DPQ and INO-1001 on ADP-, collagen- or PAR1ap-induced platelet aggregation. Human PRP samples were preincubated with PARP inhibitor (50 μM) or its vehicle and then stimulated with ADP (1.5 to 5 μM; to produce a biphasic aggregation curve), collagen (1 to 2 μg/ml) or PAR1ap (1 to 2 μM). Results are expressed relatively to platelet agonist alone (=vehicle group; normalized to 100%) and presented as the mean±SD (n=5-6). |
|
| S2197 |
A-966492A-966492 is a novel and potent inhibitor of PARP1 and PARP2 with Ki of 1 nM and 1.5 nM, respectively. |
Immunoblot analysis of PARylation after treatment with various PARP inhibitors.The asterisk indicates a nonspecific band. |
|
| S7300 |
PJ34 HClPJ34 HCl is the hydrochloride salt of PJ34, which is a PARP inhibitor with EC50 of 20 nM and is equally potent to PARP1/2. |
LN229 GBM cells were treated with PJ34 (20 µM), TRAIL (200 ng/ml) or the combination of both and analyzed for the expression of DR5, caspase-9 (CP9) and cleaved caspase-3 (cCP3). The vertical line on the immunoblot indicates that the first and second samples were noncontiguous, but run on the same gel simultaneously with the other samples.
|
|
| S2741 |
Niraparib (MK-4827)Niraparib (MK-4827) is a selective inhibitor of PARP1/2 with IC50 of 3.8 nM/2.1 nM, with great activity in cancer cells with mutant BRCA-1 and BRCA-2. It is >330-fold selective against PARP3, V-PARP and Tank1. Niraparib can form PARP–DNA complexes resulting in DNA damage, apoptosis, and cell death. Phase 3. |
PARP1 silencing rescues PARP1/2 inhibitor sensitivity in the ERCC1-deficient population. Effect of PARP1 knockdown by siRNA on sensitivity of ERCC1-isogenic cell lines to niraparib. Cells were reverse-transfected with PARP1 siRNA and drug was added 48 h after transfection. Cells were exposed to the drug for 5 days. Error bars represent the s.d. from the mean of three independent experiments.
|
|
| S8038 |
UPF 1069UPF 1069 is a selective PARP2 inhibitor with IC50 of 0.3 μM. It is ~27-fold selective against PARP1. |
||
| S7029 |
AZD2461AZD2461 is a novel PARP inhibitor with low affinity for Pgp than Olaparib. Phase 1. |
(b) Hoechst-positive cell quantification of caspase and PARP inhibitors and their effect on ARPE-19 cells undergoing UOS in the presence and absence of NPD1 (lower panel). Bars represent data averages of three repeats (technical replicas) of three independent experiments (biological replicas). *P<0.05
|
|
| S7438 |
ME0328ME0328 is a potent and selective PARP inhibitor with IC50 of 0.89 μM for PARP3, about 7-fold selectivity over PARP1. |
Colony survival assay in wild-type A549 cells treated with vehicle, 3.0 μM ME0328 or 500 nM KU58948 and pyridostatin.
|
|
| S8370 |
BGP-15 2HClBGP-15, is a nicotinic amidoxime derivative with PARP inhibitory activity. It has been demonstrated that BGP-15 protects against ischemia-reperfusion injury. |
||
| S7625 |
Niraparib (MK-4827) tosylateNiraparib tosylate (MK-4827, ZEJULA) is a selective inhibitor of PARP1/PARP2 with IC50 of 3.8 nM/2.1 nM. Niraparib increases formation of PARP-DNA complexes resulting in DNA damage, apoptosis, and cell death. |
Berberine activates PARP1 in ovarian cancer cells. PAR synthesis is detected by immunofluorescence staining in A2780 and HO8910 treated with different concentration of berberine alone or in combination with niraparib (10 μM) for 48 h. Top: representative examples of immunofluorescence staining of PAR. Scale bar, 20 μm. Bottom: quantification of PAR level in A2780 and HO8910. Immunofluorescence intensities were quantified by ImageJ. *P<0.05, **P<0.01
|
|
| S7730 |
NU1025NU1025 is a potent PARP inhibitor with IC50 of 400 nM. |
||
| S8592 |
Pamiparib (BGB-290)Pamiparib (BGB-290) is a potent and selective inhibitor of PARP1 and PARP2 with IC50 values of 0.83 and 0.11 nM, respectively in biochemical assays. It shows high selectivity over other PARP enzymes. |
||
| S7239 |
G007-LKG007-LK is a potent and selective tankyrase inhibitor with IC50 of 46 nM and 25 nM for TNKS1/2, respectively. |
Western blot analysis of SH3BP2 in WT BMMs after culture for 2 days in the presence of IWR-1 (2 μM), G007-LK (0.1 μM), or ICG001 (2 μM). |
|
| S7238 |
NVP-TNKS656NVP-TNKS656 is a highly potent, selective, and orally active tankyrase inhibitor with IC50 of 6 nM for TNKS2, > 300-fold selectivity against PARP1 and PARP2. |
||
| S8419 |
E7449E7449 is an orally bioavailable, brain penetrable, small molecule dual inhibitor of PARP1/2 and also inhibits PARP5a/5b, otherwise known as tankyrase1 and 2 (TNKS1/2), important regulators of canonical Wnt/β-catenin signaling. It has IC50 values of 1.0 and 1.2 nM for PARP1 and 2, respectively. |
||
| S9360 |
4-Hydroxyquinazoline4-Hydroxyquinazoline (Quinazolin-4-ol, 4-Quinazolinol) is a PARP inhibitor with a high potency for PARP-1 with IC50 of 9.5 μM. |
||
| S8363 |
NMS-P118NMS-P118 is a potent, orally available, and highly selective PARP-1 inhibitor endowed with excellent ADME and pharmacokinetic profiles, showing 150-fold selectivity for PARP-1 over PARP-2 (Kd 0.009 μM vs 1.39 μM, respectively). |
||
| S4715 |
BenzamideBenzamide, a derivative of benzoic acid, is an inhibitor of poly(ADP-ribose) polymerase with an IC50 of 3.3 μM. |
||
| S4710 |
PicolinamidePicolinamide is found to be a strong inhibitor of poly (ADP-ribose) synthetase of nuclei from rat pancreatic islet cells. |
||
| S2271 |
Berberine chlorideBerberine chloride is a quaternary ammonium salt from the group of isoquinoline alkaloids. Berberine activates caspase 3 and caspase 8, cleavage of poly ADP-ribose polymerase (PARP) and the release of cytochrome c. Berberine chloride decreases the expression of c-IAP1, Bcl-2 and Bcl-XL. Berberine chloride induces apoptosis with sustained phosphorylation of JNK and p38 MAPK, as well as generation of the ROS. Berberine chloride is a dual topoisomerase I and II inhibitor. Berberine chloride is also a potential autophagy modulator. |
| Catalog No. | Information | Product Use Citations | Product Validations |
|---|---|---|---|
| S1060 |
Olaparib (AZD2281)Olaparib (AZD2281, KU0059436) is a selective inhibitor of PARP1/2 with IC50 of 5 nM/1 nM in cell-free assays, 300-times less effective against tankyrase-1. Olaparib induces significant autophagy that is associated with mitophagy in cells with BRCA mutations. |
Role of PARP and BER in the synergy between PTX and GMX in A549 cells. A) Cells were pre-treated +/- 1 uM olaparib (2h) then sequentially +/- 150nM PTX (24h) then +/- GMX 12nM (48h). Cells were harvested for (left) NAD+ quantification by LC-MS/MS (mean +/-SD of quadruplicates) or (right) viability by CellTiter-Glo (mean +/-SD of duplicates) B) PAR modification of proteins and γ-H2AX levels were measured in extracts treated as in A) by western blotting.
|
|
| S1004 |
Veliparib (ABT-888)Veliparib (ABT-888, NSC 737664) is a potent inhibitor of PARP1 and PARP2 with Ki of 5.2 nM and 2.9 nM in cell-free assays, respectively. It is inactive to SIRT2. Veliparib increases autophagy and apoptosis. Phase 3. |
Number of foci detected using laser confocal microscopy and fluorescent Fluor 647 anti-H2A.X-phosphorylated (Ser139) antibody. Double-stranded breaks (red) are clearly augmented in cells incubated with 500 nmol/l of ABT-888 and 500 nmol/l of AZD-2281 compared with PBS and 1% dimethyl sulfoxide controls. Image analysis was performed using ImageJ and the ‘analyze particle’ function. |
|
| S1180 |
XAV-939XAV-939 (NVP-XAV939) selectively inhibits Wnt/β-catenin-mediated transcription through tankyrase1/2 inhibition with IC50 of 11 nM/4 nM in cell-free assays, regulates axin levels and does not affect CRE, NF-κB or TGF-β. |
Fluorescence microscopy of pSuper or Cdo shRNA expressing P19 cells at ITS1 immunostained withβ-tubulin III antibodies. Size bar=100 um. P19/control or P19/Cdo shRNA cells were treated with DMSO or XAV939 in the differentiation medium for 72 h followed by immunostaining.
|
|
| S1098 |
Rucaparib (AG-014699) phosphateRucaparib (AG-014699, PF-01367338) is an inhibitor of PARP with Ki of 1.4 nM for PARP1 in a cell-free assay, also showing binding affinity to eight other PARP domains. Phase 3. |
For anchorage dependent clonogenic assays, HER2+ breast cancer BT474 cells were seeded at low density in 6-well plates and allowed to adhere overnight. The next day, olaparib and rucaparib were added at the indicated concentrations. Media and drugs were replenished every three days. After 10-15 days, depending on cell proliferation rate, cells were fixed and stained with crystal violet. Images and graphs indicate the results compared to control condition. Data are mean ± S.D. n.s.: non-significant, ∗p < 0.05, ∗∗p < 0.01, ∗∗∗p < 0.001.
|
|
| S1087 |
Iniparib (BSI-201)Iniparib (BSI-201, NSC-746045, IND-71677) is a PARP1 inhibitor with demonstrated effectiveness in triple-negative breast cancer (TNBC). Phase 3. |
Immunoblot analysis of
PARylation after treatment with various PARP
inhibitors.The asterisk indicates
a nonspecific band.
|
|
| S8876New |
RK-287107RK-287107 is a novel, potent and selective tankyrase inhibitor with antitumor activity. RK-287107 inhibits tankyrase-1 and tankyrase-2 in vitro with IC50 of 14.3 nM and 10.6 nM. |
||
| S6739New |
MN 64MN-64 is a potent inhibitor of TNKS1 and TNKS2 with IC50 value of 6 and 72 nM, respectively. |
||
| S7048 |
Talazoparib (BMN 673)Talazoparib (BMN 673) is a novel PARP inhibitor with IC50 of 0.57 nM for PARP1 in a cell-free assay. It is also a potent inhibitor of PARP-2, but does not inhibit PARG and is highly sensitive to PTEN mutation. Phase 3. |
Western blot assessment of effects on PAR, PARP, and dsDNA breaks mediated by IMMU-132 plus PARPi in TNBC tumor lines. Cells were plated overnight in 6-well plates before the addition of chemotherapeutics. After a 24-hour incubation, cells were harvested and cell lysates resolved and transferred for Western analysis as described in Materials and Methods. PAR and FL-PARP levels were determined on the same gel. Assessment of dsDNA breaks (p-H2A.X) was calculated as ratios relative to untreated control (Unt) normalized to b-actin protein loading control (Dp-H2A.X). B, HCC1806 cells exposed to rucaparib (Ruc) and IMMU-132 or to (C) talazoparib (Tala) and IMMU-132. |
|
| S2178 |
AG-14361AG14361 is a potent inhibitor of PARP1 with Ki of <5 nM in a cell-free assay. It is at least 1000-fold more potent than the benzamides. |
Immunoblot analysis of PARylation after treatment with various PARP inhibitors.The asterisk indicates a nonspecific band. |
|
| S1132 |
INO-1001 (3-Aminobenzamide)INO-1001 (3-ABA , 3-Amino Benzamide, 3-AB) is a potent inhibitor of PARP with IC50 of <50 nM in CHO cells and a mediator of oxidant-induced myocyte dysfunction during reperfusion. Phase 2. |
Effect of DPQ and INO-1001 on ADP-, collagen- or PAR1ap-induced platelet aggregation. Human PRP samples were preincubated with PARP inhibitor (50 μM) or its vehicle and then stimulated with ADP (1.5 to 5 μM; to produce a biphasic aggregation curve), collagen (1 to 2 μg/ml) or PAR1ap (1 to 2 μM). Results are expressed relatively to platelet agonist alone (=vehicle group; normalized to 100%) and presented as the mean±SD (n=5-6). |
|
| S2197 |
A-966492A-966492 is a novel and potent inhibitor of PARP1 and PARP2 with Ki of 1 nM and 1.5 nM, respectively. |
Immunoblot analysis of PARylation after treatment with various PARP inhibitors.The asterisk indicates a nonspecific band. |
|
| S7300 |
PJ34 HClPJ34 HCl is the hydrochloride salt of PJ34, which is a PARP inhibitor with EC50 of 20 nM and is equally potent to PARP1/2. |
LN229 GBM cells were treated with PJ34 (20 µM), TRAIL (200 ng/ml) or the combination of both and analyzed for the expression of DR5, caspase-9 (CP9) and cleaved caspase-3 (cCP3). The vertical line on the immunoblot indicates that the first and second samples were noncontiguous, but run on the same gel simultaneously with the other samples.
|
|
| S2741 |
Niraparib (MK-4827)Niraparib (MK-4827) is a selective inhibitor of PARP1/2 with IC50 of 3.8 nM/2.1 nM, with great activity in cancer cells with mutant BRCA-1 and BRCA-2. It is >330-fold selective against PARP3, V-PARP and Tank1. Niraparib can form PARP–DNA complexes resulting in DNA damage, apoptosis, and cell death. Phase 3. |
PARP1 silencing rescues PARP1/2 inhibitor sensitivity in the ERCC1-deficient population. Effect of PARP1 knockdown by siRNA on sensitivity of ERCC1-isogenic cell lines to niraparib. Cells were reverse-transfected with PARP1 siRNA and drug was added 48 h after transfection. Cells were exposed to the drug for 5 days. Error bars represent the s.d. from the mean of three independent experiments.
|
|
| S8038 |
UPF 1069UPF 1069 is a selective PARP2 inhibitor with IC50 of 0.3 μM. It is ~27-fold selective against PARP1. |
||
| S7029 |
AZD2461AZD2461 is a novel PARP inhibitor with low affinity for Pgp than Olaparib. Phase 1. |
(b) Hoechst-positive cell quantification of caspase and PARP inhibitors and their effect on ARPE-19 cells undergoing UOS in the presence and absence of NPD1 (lower panel). Bars represent data averages of three repeats (technical replicas) of three independent experiments (biological replicas). *P<0.05
|
|
| S7438 |
ME0328ME0328 is a potent and selective PARP inhibitor with IC50 of 0.89 μM for PARP3, about 7-fold selectivity over PARP1. |
Colony survival assay in wild-type A549 cells treated with vehicle, 3.0 μM ME0328 or 500 nM KU58948 and pyridostatin.
|
|
| S8370 |
BGP-15 2HClBGP-15, is a nicotinic amidoxime derivative with PARP inhibitory activity. It has been demonstrated that BGP-15 protects against ischemia-reperfusion injury. |
||
| S7625 |
Niraparib (MK-4827) tosylateNiraparib tosylate (MK-4827, ZEJULA) is a selective inhibitor of PARP1/PARP2 with IC50 of 3.8 nM/2.1 nM. Niraparib increases formation of PARP-DNA complexes resulting in DNA damage, apoptosis, and cell death. |
Berberine activates PARP1 in ovarian cancer cells. PAR synthesis is detected by immunofluorescence staining in A2780 and HO8910 treated with different concentration of berberine alone or in combination with niraparib (10 μM) for 48 h. Top: representative examples of immunofluorescence staining of PAR. Scale bar, 20 μm. Bottom: quantification of PAR level in A2780 and HO8910. Immunofluorescence intensities were quantified by ImageJ. *P<0.05, **P<0.01
|
|
| S7730 |
NU1025NU1025 is a potent PARP inhibitor with IC50 of 400 nM. |
||
| S8592 |
Pamiparib (BGB-290)Pamiparib (BGB-290) is a potent and selective inhibitor of PARP1 and PARP2 with IC50 values of 0.83 and 0.11 nM, respectively in biochemical assays. It shows high selectivity over other PARP enzymes. |
||
| S7239 |
G007-LKG007-LK is a potent and selective tankyrase inhibitor with IC50 of 46 nM and 25 nM for TNKS1/2, respectively. |
Western blot analysis of SH3BP2 in WT BMMs after culture for 2 days in the presence of IWR-1 (2 μM), G007-LK (0.1 μM), or ICG001 (2 μM). |
|
| S7238 |
NVP-TNKS656NVP-TNKS656 is a highly potent, selective, and orally active tankyrase inhibitor with IC50 of 6 nM for TNKS2, > 300-fold selectivity against PARP1 and PARP2. |
||
| S8419 |
E7449E7449 is an orally bioavailable, brain penetrable, small molecule dual inhibitor of PARP1/2 and also inhibits PARP5a/5b, otherwise known as tankyrase1 and 2 (TNKS1/2), important regulators of canonical Wnt/β-catenin signaling. It has IC50 values of 1.0 and 1.2 nM for PARP1 and 2, respectively. |
||
| S9360 |
4-Hydroxyquinazoline4-Hydroxyquinazoline (Quinazolin-4-ol, 4-Quinazolinol) is a PARP inhibitor with a high potency for PARP-1 with IC50 of 9.5 μM. |
||
| S8363 |
NMS-P118NMS-P118 is a potent, orally available, and highly selective PARP-1 inhibitor endowed with excellent ADME and pharmacokinetic profiles, showing 150-fold selectivity for PARP-1 over PARP-2 (Kd 0.009 μM vs 1.39 μM, respectively). |
||
| S4715 |
BenzamideBenzamide, a derivative of benzoic acid, is an inhibitor of poly(ADP-ribose) polymerase with an IC50 of 3.3 μM. |
||
| S4710 |
PicolinamidePicolinamide is found to be a strong inhibitor of poly (ADP-ribose) synthetase of nuclei from rat pancreatic islet cells. |
| Catalog No. | Information | Product Use Citations | Product Validations |
|---|---|---|---|
| S2271 |
Berberine chlorideBerberine chloride is a quaternary ammonium salt from the group of isoquinoline alkaloids. Berberine activates caspase 3 and caspase 8, cleavage of poly ADP-ribose polymerase (PARP) and the release of cytochrome c. Berberine chloride decreases the expression of c-IAP1, Bcl-2 and Bcl-XL. Berberine chloride induces apoptosis with sustained phosphorylation of JNK and p38 MAPK, as well as generation of the ROS. Berberine chloride is a dual topoisomerase I and II inhibitor. Berberine chloride is also a potential autophagy modulator. |
