PARP
信号通路图
研究领域
抑制剂选择性比较
特异性亚型抑制剂
PARP产品
| 目录号 | 产品描述 | 文献引用 | 实验数据 |
|---|---|---|---|
| S1060 |
Olaparib (AZD2281)Olaparib (AZD2281, KU0059436)是选择性的PARP1/2抑制剂，IC50为5 nM/1 nM，其对PARP1/2的作用比对Tankyrase-1效果高300倍。在BRCA突变的细胞中，Olaparib可以显著地诱导线粒体自噬相关的细胞自噬。 |
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)是一种有效的PARP1和PARP2抑制剂，无细胞试验中Ki分别为5.2 nM和2.9 nM，对SIRT2没有活性。Veliparib 可增加自噬和凋亡。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通过抑制tankyrase1/2而选择性抑制Wnt/β-catenin介导的转录，无细胞试验中IC50为11 nM/4 nM，调节轴蛋白水平，而对 CRE， NF-κB和TGF-β无作用。 |
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)是一种PARP抑制剂，无细胞试验中作用于PARP1的Ki为1.4 nM，对其余8个PARP位点也有结合亲和力。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)是一种PARP1抑制剂，在三阴性乳腺癌(TNBC)中具有作用效果。Phase 3。 |
Immunoblot analysis of
PARylation after treatment with various PARP
inhibitors.The asterisk indicates
a nonspecific band.
|
|
| S8876New |
RK-287107RK-287107 是一种新型有效且具有选择性及抗肿瘤活性的 tankyrase 的抑制剂。RK-287107 可抑制 tankyrase-1 和 tankyrase-2，在体外实验中其IC50值为14.3 nM和10.6 nM。 |
||
| S6739New |
MN 64MN-64是有效的TNKS1和TNKS2抑制剂，IC50分别为6 nM和72 nM。 |
||
| S7048 |
Talazoparib (BMN 673)Talazoparib (BMN 673)是一种新型的PARP抑制剂，无细胞试验中对PARP1的IC50为0.57 nM。它也是有效的PARP-2抑制剂，但不抑制PARG，对PTEN突变型高度敏感。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是一种有效的PARP1抑制剂，无细胞试验中Ki为<5 nM。它比benzamides至少有效1000倍。 |
Immunoblot analysis of PARylation after treatment with various PARP inhibitors.The asterisk indicates a nonspecific band. |
|
| S1132 |
INO-1001 (3-Aminobenzamide)INO-1001是一种有效的PARP抑制剂，作用于CHO细胞的IC50为<50 nM，在再灌注期间，是一种因氧化诱导而发生的心肌功能障碍的调节剂。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是一种新型有效的PARP1和PARP2抑制剂，Ki分别为1 nM和1.5 nM。 |
Immunoblot analysis of PARylation after treatment with various PARP inhibitors.The asterisk indicates a nonspecific band. |
|
| S7300 |
PJ34 HClPJ34 HCl 是PJ34的盐酸盐形式，是一种PARP抑制剂，EC50为20 nM，同等有效作用于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 (MK4827)是一种口服有效的选择性PARP-1和PARP-2抑制剂，可在有BRCA和PTEN功能缺陷的临床肿瘤模型中引起合成致死性。Niraparib 可形成PARP–DNA复合物并导致DNA损伤、凋亡和细胞死亡。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是一种选择性PARP2抑制剂，IC50为0.3 μM，比作用于PARP1选择性高27倍左右。 |
||
| S7029 |
AZD2461AZD2461是一种新型PARP抑制剂，作用于Pgp比Olaparib亲和力低。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 是一种强效的选择性的PARP抑制剂，IC50为0.89 μM，其作用于PARP3的选择性比作用于PARP1的选择性高约七倍。 |
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是具有PARP抑制活性的烟酸胺肟衍生物。BGP-15被发现能够在缺血再灌注损伤后起到保护作用。 |
||
| S7625 |
Niraparib (MK-4827) tosylateNiraparib (MK-4827) tosylate是PARP1/PARP2的选择性抑制剂，IC50分别为3.8 nM和2.1 nM。Niraparib可增加PARP-DNA复合体的形成，并导致DNA损伤、凋亡和细胞死亡。 |
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 是一种有效的 PARP 抑制剂，IC50 为 400 nM。 |
||
| S8592 |
Pamiparib (BGB-290)Pamiparib (BGB-290)是有效的PARP1和PARP2选择性抑制剂，IC50分别为0.83和0.11 nM。相较于其他PARP酶，它对PARP1和PARP2具有高选择性。 |
||
| S7239 |
G007-LKG007-LK是一种有效的选择性tankyrase抑制剂，对TNKS1/2的IC50分别为46 nM 和 25 nM。 |
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是一种高度有效的，选择性的，口服具有活性的tankyrase抑制剂，对 TNKS2 的IC50为6 nM，选择性比作用于PARP1和PARP2高300多倍。 |
||
| S8419 |
E7449E7449是一种具有生物口服活性的、能够通过血脑屏障的PARP1/2双效小分子化合物抑制剂，同样还能抑制PARP5a/5b（即TNKS1/2）。对PARP1和PARP2的IC50分别为1 nM和1.2 nM。 |
||
| S9360 |
4-Hydroxyquinazoline |
||
| S8363 |
NMS-P118NMS-P118是一种有效的、具有口服活性、高度选择性的PARP-1抑制剂，具有良好的药物吸收和药物动力学特性，对PARP1的选择性比对PARP2高150倍（Kd 0.009 μM vs 1.39 μM） |
||
| S4715 |
BenzamideBenzamide, PARP的抑制剂，IC50为3.3 μM。它是苯甲酸的一种衍生物。 |
||
| S4710 |
PicolinamidePicolinamide在大鼠胰岛细胞核中，是一种强效的PARP抑制剂。 |
| 目录号 | 产品描述 | 文献引用 | 实验数据 |
|---|---|---|---|
| S1060 |
Olaparib (AZD2281)Olaparib (AZD2281, KU0059436)是选择性的PARP1/2抑制剂，IC50为5 nM/1 nM，其对PARP1/2的作用比对Tankyrase-1效果高300倍。在BRCA突变的细胞中，Olaparib可以显著地诱导线粒体自噬相关的细胞自噬。 |
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)是一种有效的PARP1和PARP2抑制剂，无细胞试验中Ki分别为5.2 nM和2.9 nM，对SIRT2没有活性。Veliparib 可增加自噬和凋亡。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通过抑制tankyrase1/2而选择性抑制Wnt/β-catenin介导的转录，无细胞试验中IC50为11 nM/4 nM，调节轴蛋白水平，而对 CRE， NF-κB和TGF-β无作用。 |
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)是一种PARP抑制剂，无细胞试验中作用于PARP1的Ki为1.4 nM，对其余8个PARP位点也有结合亲和力。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)是一种PARP1抑制剂，在三阴性乳腺癌(TNBC)中具有作用效果。Phase 3。 |
Immunoblot analysis of
PARylation after treatment with various PARP
inhibitors.The asterisk indicates
a nonspecific band.
|
|
| S8876New |
RK-287107RK-287107 是一种新型有效且具有选择性及抗肿瘤活性的 tankyrase 的抑制剂。RK-287107 可抑制 tankyrase-1 和 tankyrase-2，在体外实验中其IC50值为14.3 nM和10.6 nM。 |
||
| S6739New |
MN 64MN-64是有效的TNKS1和TNKS2抑制剂，IC50分别为6 nM和72 nM。 |
||
| S7048 |
Talazoparib (BMN 673)Talazoparib (BMN 673)是一种新型的PARP抑制剂，无细胞试验中对PARP1的IC50为0.57 nM。它也是有效的PARP-2抑制剂，但不抑制PARG，对PTEN突变型高度敏感。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是一种有效的PARP1抑制剂，无细胞试验中Ki为<5 nM。它比benzamides至少有效1000倍。 |
Immunoblot analysis of PARylation after treatment with various PARP inhibitors.The asterisk indicates a nonspecific band. |
|
| S1132 |
INO-1001 (3-Aminobenzamide)INO-1001是一种有效的PARP抑制剂，作用于CHO细胞的IC50为<50 nM，在再灌注期间，是一种因氧化诱导而发生的心肌功能障碍的调节剂。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是一种新型有效的PARP1和PARP2抑制剂，Ki分别为1 nM和1.5 nM。 |
Immunoblot analysis of PARylation after treatment with various PARP inhibitors.The asterisk indicates a nonspecific band. |
|
| S7300 |
PJ34 HClPJ34 HCl 是PJ34的盐酸盐形式，是一种PARP抑制剂，EC50为20 nM，同等有效作用于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 (MK4827)是一种口服有效的选择性PARP-1和PARP-2抑制剂，可在有BRCA和PTEN功能缺陷的临床肿瘤模型中引起合成致死性。Niraparib 可形成PARP–DNA复合物并导致DNA损伤、凋亡和细胞死亡。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是一种选择性PARP2抑制剂，IC50为0.3 μM，比作用于PARP1选择性高27倍左右。 |
||
| S7029 |
AZD2461AZD2461是一种新型PARP抑制剂，作用于Pgp比Olaparib亲和力低。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 是一种强效的选择性的PARP抑制剂，IC50为0.89 μM，其作用于PARP3的选择性比作用于PARP1的选择性高约七倍。 |
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是具有PARP抑制活性的烟酸胺肟衍生物。BGP-15被发现能够在缺血再灌注损伤后起到保护作用。 |
||
| S7625 |
Niraparib (MK-4827) tosylateNiraparib (MK-4827) tosylate是PARP1/PARP2的选择性抑制剂，IC50分别为3.8 nM和2.1 nM。Niraparib可增加PARP-DNA复合体的形成，并导致DNA损伤、凋亡和细胞死亡。 |
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 是一种有效的 PARP 抑制剂，IC50 为 400 nM。 |
||
| S8592 |
Pamiparib (BGB-290)Pamiparib (BGB-290)是有效的PARP1和PARP2选择性抑制剂，IC50分别为0.83和0.11 nM。相较于其他PARP酶，它对PARP1和PARP2具有高选择性。 |
||
| S7239 |
G007-LKG007-LK是一种有效的选择性tankyrase抑制剂，对TNKS1/2的IC50分别为46 nM 和 25 nM。 |
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是一种高度有效的，选择性的，口服具有活性的tankyrase抑制剂，对 TNKS2 的IC50为6 nM，选择性比作用于PARP1和PARP2高300多倍。 |
||
| S8419 |
E7449E7449是一种具有生物口服活性的、能够通过血脑屏障的PARP1/2双效小分子化合物抑制剂，同样还能抑制PARP5a/5b（即TNKS1/2）。对PARP1和PARP2的IC50分别为1 nM和1.2 nM。 |
||
| S9360 |
4-Hydroxyquinazoline |
||
| S8363 |
NMS-P118NMS-P118是一种有效的、具有口服活性、高度选择性的PARP-1抑制剂，具有良好的药物吸收和药物动力学特性，对PARP1的选择性比对PARP2高150倍（Kd 0.009 μM vs 1.39 μM） |
||
| S4715 |
BenzamideBenzamide, PARP的抑制剂，IC50为3.3 μM。它是苯甲酸的一种衍生物。 |
||
| S4710 |
PicolinamidePicolinamide在大鼠胰岛细胞核中，是一种强效的PARP抑制剂。 |
沪公网安备 31011502012800号