Journal: Molecules

Article Title: Development of Novel Pyridine-Thiazole Hybrid Molecules as Potential Anticancer Agents

doi: 10.3390/molecules27196219

Figure Lengend Snippet: Preincubation of MCF-7 cells with PARP1 inhibitor Fluzoparib decreased their sensitivity to the treatment with compounds 4 ( A ) and 3 ( B ). MTT data on 72 h of cells incubation with studied compounds 3 and 4 (** p < 0.01, *** p < 0.001, **** p < 0.0001).

Article Snippet: To determine PARP inactivation, the MCF-7 cells were pretreated for 2 h in the non-toxic concentrations of 5, 10, 15 µM of the Fluzoparib (Med Chem Express, Monmouth Junction, NJ, USA), a potent PARP1 inhibitor used in the chemotherapy [ ].

Techniques: Incubation

Journal: Molecules

Article Title: Development of Novel Pyridine-Thiazole Hybrid Molecules as Potential Anticancer Agents

doi: 10.3390/molecules27196219

Figure Lengend Snippet: Docking scores of the studied compounds.

Article Snippet: To determine PARP inactivation, the MCF-7 cells were pretreated for 2 h in the non-toxic concentrations of 5, 10, 15 µM of the Fluzoparib (Med Chem Express, Monmouth Junction, NJ, USA), a potent PARP1 inhibitor used in the chemotherapy [ ].

Techniques: Binding Assay, Inhibition

Journal: Biochemistry

Article Title: Slow Dissociation from the PARP1–HPF1 Complex Drives Inhibitor Potency

doi: 10.1021/acs.biochem.3c00243

Figure Lengend Snippet: Olaparib associates with PARP1 in a concentration-dependent manner. (A–C) Representative graphs showing the changes in the FP signal over time following the addition of NAD + to a complex of PARP1, p18mer*, and olaparib (10 nM in A, 20 nM in B, and 40 nM in C) at varying delay times (1.5–150 s) following addition of olaparib. Each line in the graph corresponds to the indicated delay time after addition of olaparib. The replots (measured linear rates vs delay times) are shown on the right for each graph of the primary data and reveal the apparent rate of association ( k obs ) under the experimental conditions. (D) The graph shown is a re-replot of the k obs derived from the replots shown in the insets of (A–C) vs the concentration of olaparib. The linear dependence of these k obs demonstrates a simple one-step mechanism of association. The other PARPi that were subjected to this concentration-dependent experiment (fluzoparib, talazoparib, and saruparib) are shown in Figures S1–S3 .

Article Snippet: Veliparib (S1004), olaparib (S1060), fluzoparib (S9712), rucaparib (S1098), niraparib (S2741), and talazoparib (S7048) were purchased from Selleck.

Techniques: Concentration Assay, Derivative Assay

Journal: Biochemistry

Article Title: Slow Dissociation from the PARP1–HPF1 Complex Drives Inhibitor Potency

doi: 10.1021/acs.biochem.3c00243

Figure Lengend Snippet: Rates of association of PARPi to PARP1 or the PARP1–HPF1 complex. Representative graphs demonstrate that veliparib (A) has a significantly faster rate of association with PARP1 ( k on ) compared to AZD9574 (B). The raw data in the left graphs show the loss in FP signal after the addition of NAD + to a mixture of PARP1, p18mer, and 20 nM PARPi at different delay times between 10 and 250 s. The replot graphs on the right (measured linear rates vs delay times) are used to calculate the actual k on values for veliparib and AZD9574. (C) Summary of rates of association of PARPi to PARP1 or PARP1–HPF1 complex. Rates of association for each PARPi with PARP1 (lighter shade, left bar of each pair) and PARP1–HPF1 complex (darker shade, right bar of each pair) as averages with standard deviations. Pairwise statistical comparison demonstrates differences ( p < 0.05) following the addition of HPF1 for fluzoparib, niraparib, and saruparib. Values for k on and number of replicates are shown in Table , and representative data for each PARPi are shown in Figures A,B, S4, and S6 .

Article Snippet: Veliparib (S1004), olaparib (S1060), fluzoparib (S9712), rucaparib (S1098), niraparib (S2741), and talazoparib (S7048) were purchased from Selleck.

Techniques: Comparison

Journal: Biochemistry

Article Title: Slow Dissociation from the PARP1–HPF1 Complex Drives Inhibitor Potency

doi: 10.1021/acs.biochem.3c00243

Figure Lengend Snippet: Measuring the binding affinity of fluzoparib, saruparib, and AZD9574 for PARP1 or PARP1 ± HPF1. Representative data measuring the release of p18mer* from PARP1 in the presence of varying concentrations (as indicated on the right) of the fluzoparib (A), saruparib (B), and AZD9574 (C). The lines through the points reflect fitting to first-order kinetics, and the data were processed to derive K i values as previously described. Results of replicate experiments are shown in Table .

Article Snippet: Veliparib (S1004), olaparib (S1060), fluzoparib (S9712), rucaparib (S1098), niraparib (S2741), and talazoparib (S7048) were purchased from Selleck.

Techniques: Binding Assay

Journal: Biochemistry

Article Title: Slow Dissociation from the PARP1–HPF1 Complex Drives Inhibitor Potency

doi: 10.1021/acs.biochem.3c00243

Figure Lengend Snippet: Measured Rates of Association ( k on ) for PARPi to PARP1 ± HPF1 a

Article Snippet: Veliparib (S1004), olaparib (S1060), fluzoparib (S9712), rucaparib (S1098), niraparib (S2741), and talazoparib (S7048) were purchased from Selleck.

Techniques:

Journal: American Journal of Cancer Research

Article Title: Synergism of PARP inhibitor fluzoparib (HS10160) and MET inhibitor HS10241 in breast and ovarian cancer cells

doi:

Figure Lengend Snippet: HS10160 inhibits H2O2-induced PARylation in TNBC and HGSOC cell lines. Human TNBC cells (BT549 and MDA-MB-231) and HGSOC cells (DOV13 and OVCA433) were treated with indicated concentrations of PARP inhibitor HS10160 for 3 h prior to 30 min 20 mM H2O2 treatment. Cells were then subjected to Western blot analysis to determine PARylation (PAR) and PARP1 expression. Actin were used as protein quantity loading control among different samples.

Article Snippet: Fluzoparib (HS10160) and HS10241 were kindly provided by Jiangsu Hengrui Medicine Co. Ltd (Shanghai, China).

Techniques: Western Blot, Expressing, Control

Journal: American Journal of Cancer Research

Article Title: Synergism of PARP inhibitor fluzoparib (HS10160) and MET inhibitor HS10241 in breast and ovarian cancer cells

doi:

Figure Lengend Snippet: Combination of HS10241 and HS10160 induces formation of double strand DNA breaks and eliminate cancer cell synergistically. A-D. Double strand DNA breaks are indicated by measuring γ-H2AX foci through the use of immunofluorescence staining and confocal microscope. Cells indicated were treated with HS10160 (10 µM) and HS-10241 (10 µM) alone or in combination for 18 h before immunofluorescence staining. Representative images of γ-H2AX are shown. Percentages of treated cells containing γ-H2AX foci (γH2AX positive) were summarized from counting 100 cells in each samples. Cells treated with 20 mM H2O2 for 20 min were used as positive control of γH2AX induction. Histograms shown represent mean and standard deviations among 3 repeats. E-H. Synergism was assessed by the Chou-Talalay method. Cells were treated with various concentrations of HS10241 and HS10160 either alone or in combination. Cell survival is measured by using MTT assay. The combination index (CI) for each pair of agents in each cell line were calculated and plotted by using the Compusyn software.

Article Snippet: Fluzoparib (HS10160) and HS10241 were kindly provided by Jiangsu Hengrui Medicine Co. Ltd (Shanghai, China).

Techniques: Immunofluorescence, Staining, Microscopy, Positive Control, MTT Assay, Software

Journal: Cancers

Article Title: Promises of Protein Kinase Inhibitors in Recalcitrant Small-Cell Lung Cancer: Recent Scenario and Future Possibilities

doi: 10.3390/cancers16050963

Figure Lengend Snippet: A list of ICI clinical trials with their protein kinase (PK) inhibitors for SCLC.

Article Snippet: Another PARP inhibitor, Fluzoparib (also known as SHR-3162, manufactured by Jiangsu Hengrui Medicine Co Ltd., Lianyungang, China), is currently being evaluated in concert with an anti-PD-1 antibody in an open-label, phase II clinical trial (NCT04782089) in patients with ES-SCLC who did not improve after first-line chemotherapy. summarizes the protein kinase (PK) inhibitors being tested in different clinical trials for SCLC.

Techniques: Clinical Proteomics, Activation Assay, Expressing, In Vivo, Inhibition