keyword
MENU ▼
Read by QxMD icon Read
search

PARP inhibitor

keyword
https://www.readbyqxmd.com/read/29340034/prexasertib-a-cell-cycle-checkpoint-kinases-1-and-2-inhibitor-increases-in-vitro-toxicity-of-parp-inhibition-by-preventing-rad51-foci-formation-in-brca-wild-type-high-grade-serous-ovarian-cancer
#1
Ethan Brill, Takuhei Yokoyama, Jayakumar Nair, Minshu Yu, Yeong-Ran Ahn, Jung-Min Lee
PARP inhibitors (PARPi) have been effective in high-grade serous ovarian cancer (HGSOC), although clinical activity is limited against BRCA wild type HGSOC. The nearly universal loss of normal p53 regulation in HGSOCs causes dysfunction in the G1/S checkpoint, making tumor cells reliant on Chk1-mediated G2/M cell cycle arrest for DNA repair. Therefore, Chk1 is a reasonable target for a combination strategy with PARPi in treating BRCA wild type HGSOC. Here we investigated the combination of prexasertib mesylate monohydrate (LY2606368), a Chk1 and Chk2 inhibitor, and a PARP inhibitor, olaparib, in HGSOC cell lines (OVCAR3, OV90, PEO1 and PEO4) using clinically attainable concentrations...
December 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29339456/parp-inhibition-prevents-ethanol-induced-neuroinflammatory-signaling-and-neurodegeneration-in-adult-age-rat-brain-slice-cultures
#2
Nuzhath F Tajuddin, Hee-Yong Kim, Michael A Collins
Utilizing rat adult-age hippocampal-entorhinal cortical (HEC) slice cultures we examined the role of poly [ADP-ribose] polymerase (PARP) in binge ethanol's brain inflammatory and neurodegenerative mechanisms. Activated by DNA strand breaks, PARP (principally PARP1 in brain) promotes DNA repair via poly [ADP-ribose] (PAR) products, but PARP overactivation triggers regulated neuronal necrosis, e.g., parthanatos. Previously we found that brain PARP1 levels were upregulated by neurotoxic ethanol binges in adult rats and HEC slices, and PARP inhibitor PJ34 abrogated slice neurodegeneration...
January 16, 2018: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/29339439/idh1-2-mutations-sensitize-acute-myeloid-leukemia-to-parp-inhibition-and-this-is-reversed-by-idh1-2-mutant-inhibitors
#3
Remco J Molenaar, Tomas Radivoyevitch, Yasunobu Nagata, Mohammed Khurshed, Bartlomiej Przychodzen, Hideki Makishima, Mingjiang Xu, Fonnet E Bleeker, Johanna W Wilmink, Hetty Carraway, Sudipto Mukherjee, Mikkael A Sekeres, Cornelis J F Van Noorden, Jaroslaw P Maciejewski
PURPOSE: Somatic mutations in IDH1/2 occur in ~20% of patients with myeloid neoplasms, including acute myeloid leukemia (AML). IDH1/2MUT enzymes produce D-2-hydroxyglutarate (D2HG), which associates with increases in DNA damage and improved responses to chemo/radiotherapy and PARP inhibitors in solid tumor cells. Whether this also holds true for IDH1/2MUT AML is not known. EXPERIMENTAL DESIGN: Well-characterized primary IDH1MUT, IDH2MUT and IDH1/2WT AML cells were analyzed for DNA damage and responses to daunorubicin, ionizing radiation and PARP inhibitors...
January 16, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29337590/novel-mechanism-for-nicotinamide-phosphoribosyltransferase-inhibition-of-tnf-%C3%AE-mediated-apoptosis-in-human-lung-endothelial-cells
#4
Radu C Oita, Sara M Camp, Wenli Ma, Ermelinda Ceco, Mark Harbeck, Patrick Singleton, Joe Messana, Xiaoguang Sun, Ting Wang, Joe G N Garcia
Nicotinamide phosphoribosyltransferase (NAMPT) exists as both intracellular (iNAMPT) and extracellular (eNAMPT) proteins. eNAMPT is secreted into the blood and functions as a cytokine/enzyme (cytozyme) that activates NFκB signaling via ligation of the TLR4 receptor, further serving as a biomarker for inflammatory lung disorders such as the acute respiratory distress syndrome (ARDS). In contrast, iNAMPT is involved in nicotinamide mononucleotide (NMN) synthesis and has been implicated in the regulation of cellular apoptosis, although the exact mechanisms for this regulation are poorly understood...
January 16, 2018: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/29335205/design-and-synthesis-of-2-4-5-6-7-tetrahydrothienopyridin-2-yl-benzoimidazole-carboxamides-as-novel-orally-efficacious-poly-adp-ribose-polymerase-parp-inhibitors
#5
Xuxing Chen, Xiajuan Huan, Qiufeng Liu, Yuqin Wang, Qian He, Cun Tan, Yi Chen, Jian Ding, Yechun Xu, Zehong Miao, Chunhao Yang
The nuclear protein poly(ADP-ribose) polymerases-1/2 (PARP-1/2) are involved in DNA repair damaged by endogenous or exogenous process. And PARP-1/2 inhibitors have been proved to be clinically efficacious for DNA repair deficient tumors in the past decade. We have developed a series of 4,5,6,7-tetrahydrothienopyridin-2-yl benzimidazole carboxamides as novel and potent PARP-1/2 inhibitors. The best compound resulted from this series is compound 27 which displays excellent PARP-1 and PARP-2 inhibitory activity with IC50 of 18 nM and 42 nM, respectively...
January 8, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29332790/ultrasensitive-electrochemical-detection-of-poly-adp-ribose-polymerase-1-via-polyaniline-deposition
#6
Yong Liu, Jiahui Fan, Li Shangguan, Yuanjian Liu, Yuanqing Wei, Wei Wei, Songqin Liu
Recent findings have thrust poly ADP (ADP: adenosine diphosphate)-ribose polymerase-1 (PARP-1) into the limelight as potential chemotherapeutic target because it is closely related to the development of tumor. So, studies on its detection and inhibitors evaluation have attracted more attention. It is interesting that poly (ADP-ribose) (PAR), the catalytic product of PARP-1 in the existence of nicotinamide adenine dinucleotide (NAD+), possess twice charge density of DNA strands. PAR contain 200 units, i.e., about 400bp bases, and multiple branched strands...
April 1, 2018: Talanta
https://www.readbyqxmd.com/read/29330466/target-engagement-imaging-of-parp-inhibitors-in-small-cell-lung-cancer
#7
Brandon Carney, Susanne Kossatz, Benjamin H Lok, Valentina Schneeberger, Kishore K Gangangari, Naga Vara Kishore Pillarsetty, Wolfgang A Weber, Charles M Rudin, John T Poirier, Thomas Reiner
Insufficient chemotherapy response and rapid disease progression remain concerns for small-cell lung cancer (SCLC). Oncologists rely on serial CT scanning to guide treatment decisions, but this cannot assess in vivo target engagement of therapeutic agents. Biomarker assessments in biopsy material do not assess contemporaneous target expression, intratumoral drug exposure, or drug-target engagement. Here, we report the use of PARP1/2-targeted imaging to measure target engagement of PARP inhibitors in vivo. Using a panel of clinical PARP inhibitors, we show that PARP imaging can quantify target engagement of chemically diverse small molecule inhibitors in vitro and in vivo...
January 12, 2018: Nature Communications
https://www.readbyqxmd.com/read/29328447/high-mobility-group-protein%C3%A2-b1-silencing-promotes-susceptibility-of-retinoblastoma-cells-to-chemotherapeutic-drugs-through-downregulating-nuclear-factor-%C3%AE%C2%BAb
#8
Yong Chai, Juhua Xiao, Shouhua Zhang, Yunyan Du, Zhipeng Luo, Xin Zhou, Kai Huang
The aim of the present study was to investigate the effects of high-mobility group protein B1 (HMGB1) silencing on the susceptibility of retinoblastoma (RB) cells to chemotherapeutic drugs and the underlying molecular mechanisms. Western blot analysis revealed that vincristine (VCR), etoposide (ETO) and carboplatin (CBP) significantly increased the expression of HMGB1 in Weri‑Rb-1 and Y79 cells compared with the untreated control (P<0.01). siRNA HMGB1 and siRNA negative control (NC) were transfected to Y79 cells by Lipofectamine™ 2000 and, following VCR treatment, the expression of HMGB1 and nuclear factor-κB (NF-κB) was analyzed...
January 10, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29327913/proteomic-analysis-of-the-downstream-signaling-network-of-parp1
#9
Yuanli Zhen, Yonghao Yu
Poly-ADP-ribosylation (PARylation) is a protein posttranslational modification (PTM) that is critically involved in many biological processes that are linked to cell stress responses. It is catalyzed by a class of enzymes known as poly-ADP-ribose polymerases (PARPs). In particular, PARP1 is a nuclear protein that is activated upon sensing nicked DNA. Once activated, PARP1 is responsible for the synthesis of a large number of PARylated proteins and initiation of the DNA damage response (DDR) mechanisms. This observation provided the rationale for developing PARP1 inhibitors for the treatment of human malignancies...
January 12, 2018: Biochemistry
https://www.readbyqxmd.com/read/29327278/nicotinamide-inhibits-ethanol-induced-caspase-3-and-parp-1-over-activation-and-subsequent-neurodegeneration-in-the-developing-mouse-cerebellum
#10
Alessandro Ieraci, Daniel G Herrera
Fetal alcohol spectrum disorder (FASD) is the principal preventable cause of mental retardation in the western countries resulting from alcohol exposure during pregnancy. Ethanol-induced massive neuronal cell death occurs mainly in immature neurons during the brain growth spurt period. The cerebellum is one of the brain areas that are most sensitive to ethanol neurotoxicity. Currently, there is no effective treatment that targets the causes of these disorders and efficient treatments to counteract or reverse FASD are desirable...
January 11, 2018: Cerebellum
https://www.readbyqxmd.com/read/29322231/the-effect-of-food-on-the-pharmacokinetics-of-niraparib-a-poly-adp-ribose-polymerase-parp-inhibitor-in-patients-with-recurrent-ovarian-cancer
#11
Kathleen Moore, Zhi-Yi Zhang, Shefali Agarwal, Howard Burris, Manish R Patel, Vikram Kansra
PURPOSE: Niraparib is a highly selective inhibitor of PARP-1 and PARP-2 approved in the United States for maintenance treatment of adult patients with recurrent ovarian cancer in complete or partial response to platinum-based chemotherapy. In this open-label crossover study, we evaluated the effects of food on niraparib pharmacokinetics (PK) and safety. METHODS: Patients received a single 300-mg dose of niraparib either after a high-fat meal or under fasting conditions...
January 10, 2018: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/29317476/parp-inhibitor-pj34-attenuated-hepatic-triglyceride-accumulation-in-alcoholic-fatty-liver-disease-in-mice
#12
Shishun Huang, Bing Zhang, Yingli Chen, Huan Liu, Yang Liu, Xin Li, Zhiwei Bao, Zhenyuan Song, Zhigang Wang
Poly ADP ribose polymerase (PARP) is a NAD-consuming enzyme and its specific role in the pathogenesis of alcoholic fatty liver disease (AFLD) is still elusive. In current study, we applied PJ34 to inhibit hepatic PARP activity to examine the corresponding pathological alteration in AFLD in mice and the underlying molecular mechanism. We found that PJ34 decreased the intracellular TG content in hepatocyte. Moreover, PJ34 suppressed the gene expression of DGAT1 and DGAT2 and elevated the intracellular NAD+ level in hepatocyte...
January 9, 2018: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/29316839/identification-of-poly-adp-ribose-polymerase-macrodomain-inhibitors-using-an-alphascreen-protocol
#13
Torun Ekblad, Patricia Verheugd, Anders E Lindgren, Tomas Nyman, Mikael Elofsson, Herwig Schüler
Macrodomains recognize intracellular adenosine diphosphate (ADP)-ribosylation resulting in either removal of the modification or a protein interaction event. Research into compounds that modulate macrodomain functions could make important contributions. We investigated the interactions of all seven individual macrodomains of the human poly(ADP-ribose) polymerase (PARP) family members PARP9, PARP14, and PARP15 with five mono-ADP-ribosylated (automodified) ADP-ribosyltransferase domains using an AlphaScreen assay...
January 1, 2018: SLAS Discovery
https://www.readbyqxmd.com/read/29313488/replication-study-systematic-identification-of-genomic-markers-of-drug-sensitivity-in-cancer-cells
#14
John P Vanden Heuvel, Ewa Maddox, Samar W Maalouf, Elizabeth Iorns, Rachel Tsui, Alexandria Denis, Nicole Perfito, Timothy M Errington
In 2016, as part of the Reproducibility Project: Cancer Biology, we published a Registered Report (Vanden Heuvel et al., 2016), that described how we intended to replicate selected experiments from the paper 'Systematic identification of genomic markers of drug sensitivity in cancer cells' (Garnett et al., 2012). Here we report the results. We found Ewing's sarcoma cell lines, overall, were more sensitive to the PARP inhibitor olaparib than osteosarcoma cell lines; however, while the effect was in the same direction as the original study (Figure 4C; Garnett et al...
January 9, 2018: ELife
https://www.readbyqxmd.com/read/29313279/a-phase-1-study-of-parp-inhibitor-abt-767-in-advanced-solid-tumors-with-brca1-2-mutations-and-high-grade-serous-ovarian-fallopian-tube-or-primary-peritoneal-cancer
#15
Diane A J van der Biessen, Jourik A Gietema, Maja J A de Jonge, Ingrid M E Desar, Martha W den Hollander, Matthew Dudley, Martin Dunbar, Robert Hetman, Camille Serpenti, Hao Xiong, Rajendar K Mittapalli, Kirsten M Timms, Peter Ansell, Christine K Ratajczak, Stacie Peacock Shepherd, Carla M L van Herpen
Purpose This phase 1 study examined safety, pharmacokinetics (PK), and efficacy of the poly(ADP-ribose) polymerase (PARP) inhibitor ABT-767 in patients with advanced solid tumors and BRCA1/2 mutations or with high-grade serous ovarian, fallopian tube, or primary peritoneal cancer. Methods Patients received ABT-767 monotherapy orally until disease progression or unacceptable toxicity. Dose was escalated from 20 mg once daily to 500 mg twice daily (BID). Dose-limiting toxicities, recommended phase 2 dose (RP2D), food effect, objective response rate, and biomarkers predicting response were determined...
January 8, 2018: Investigational New Drugs
https://www.readbyqxmd.com/read/29305928/anti-proliferative-activity-of-biochanin-a-in-human-osteosarcoma-cells-via-mitochondrial-involved-apoptosis
#16
Yen-Nien Hsu, Huey-Wen Shyu, Tsui-Wen Hu, Jou-Pei Yeh, Ya-Wen Lin, Ling-Yi Lee, Yao-Tsung Yeh, Hong-Ying Dai, Daw-Shyong Perng, Shu-Hui Su, Yu-Hsuan Huang, Shu-Jem Su
Biochanin A is a major isoflavone in red clover and a potent chemopreventive agent against cancer. However, the effects of biochanin A on human osteosarcoma cells have never been clarified. This study investigated the anti-proliferative potential of biochanin A in osteosarcoma cells. The results indicate that biochanin A inhibited cell growth and colony formation in a dose-dependent manner with a minimal toxicity to normal cells. The combination of doxorubicin and biochanin A could synergistically inhibit osteosarcoma cell growth...
January 3, 2018: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/29304495/fphpb-inhibits-gastric-tumor-cell-proliferation-by-inducing-g2-m-cell-cycle-arrest
#17
Lei Xue, Zhijun Wu, Jinyuan Liu, Jinhua Luo
Gastric cancer is a common cancer in the world with high morbidity and mortality. Here, we report that FPHPB (4-(4-(2-fluoropyridin-3-yl)phenyl)-N-(4-hydroxyphenyl)), a derivative of CMPD-1/MK2a Inhibitor, had anti-tumor activities by inhibiting gastric tumor SNU-16 and SGC7901 cells. FPHPB dose-dependently inhibited cell proliferation, induced cell apoptosis and arrested SNU-16 and SGC7901 cells in G2-M cell cycle checkpoint. Upon treatment with FPHPB, apoptotic proteins cleaved PARP and cleaved caspase-3 were remarkably increased, and G2-M regulatory molecules, the phosphorylation of Cdc2 and Chk2, were significantly accentuated...
January 2, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29295651/mcc950-the-selective-nlrp3-inflammasome-inhibitor-protects-mice-against-traumatic-brain-injury
#18
Saifudeen Ismael, Sanaz Nasoohi, Tauheed Ishrat
NNucleotide oligomerization domain (NOD)-like receptor protein-3 (NLRP3) inflammasome may intimately contribute to sustaining damage following traumatic brain injury (TBI). This study aims to examine whether specific modulation of NLPR3 inflammasome by MCC950, a novel selective NLRP3 inhibitor confers protection after experimental TBI. Unilateral cortical impact injury was induced in young adult C57BL/6 mice. MCC950 (50 mg/kg, i.p.) or saline was administration at 1 h and 3 h post TBI. Animals were tested for neurological function, and then sacrificed for edema at 24 or 72 h post TBI...
January 2, 2018: Journal of Neurotrauma
https://www.readbyqxmd.com/read/29290992/oridonin-synergistically-enhances-jq1-triggered-apoptosis-in-hepatocellular-cancer-cells-through-mitochondrial-pathway
#19
Hua-Peng Zhang, Gong-Quan Li, Wen-Zhi Guo, Guang-Hui Chen, Hong-Wei Tang, Bing Yan, Jie Li, Jia-Kai Zhang, Pei-Hao Wen, Zhi-Hui Wang, Jian-Feng Lv, Shui-Jun Zhang
Bromodomain and Extra-Terminal Domain (BET) inhibitors, such as JQ1 have emerged as novel drug candidates and are being enthusiastically pursued in clinical trials for the treatment of cancer. However, many solid cancers are resistance to BET inhibitors. To explore methods for improving the therapeutic potential of BET inhibitors, we investigated the combinational activity of JQ1 with Oridonin, a bioactive molecules derived from Traditional Chinese Medicine in hepatocellular carcinoma (HCC) cells. Our results showed that Oridonin synergistically enhanced the abilities of JQ1 to inhibit cell viability in HCC cells and, significantly augmented JQ1-triggered apoptosis in HCC cells and in HCC cancer stem-like cells...
December 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/29285650/synergistic-cytotoxicity-of-the-dipeptidyl-peptidase-iv-inhibitor-gemigliptin-with-metformin-in-thyroid-carcinoma-cells
#20
Si Hyoung Kim, Jun Goo Kang, Chul Sik Kim, Sung-Hee Ihm, Moon Gi Choi, Hyung Joon Yoo, Seong Jin Lee
PURPOSE: The influence of the dipeptidyl peptidase-IV inhibitor, gemigliptin alone or in combination with metformin on survival, proliferation, and migration of thyroid carcinoma cells was investigated. METHODS: SW1736 and TPC-1 human thyroid carcinoma cells were used. RESULTS: Gemigliptin and metformin caused cell death in a dose-dependent manner. In cells treated with both gemigliptin and metformin, compared with metformin alone, all of the combination index values were lower than 1...
December 28, 2017: Endocrine
keyword
keyword
26589
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"